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Persons using assistive technology might not be able to fully access information in this file. For assistance, please send e-mail to: mmwrq@cdc.gov. Type 508 Accommodation and the title of the report in the subject line of e-mail. 1999 USPHS/IDSA Guidelines for the Prevention of Opportunistic Infections in Persons Infected with Human Immunodeficiency VirusU.S. Public Health Service (USPHS) and Infectious Diseases Society of America (IDSA)USPHS/IDSA Prevention of Opportunistic Infections Working Group CHAIRMEN Henry Masur, M.D., Jonathan E. Kaplan, M.D., King K. Holmes, M.D., Ph.D., MEMBERS Beverly L. Alston, M.D., Neil Ampel, M.D. Jean R. Anderson, M.D. A. Cornelius Baker David Barr John G. Bartlett, M.D. John E. Bennett, M.D. Constance A. Benson, M.D. Samual A. Bozzette, M.D. Richard E. Chaisson, M.D. Clyde S. Crumpacker, M.D. Judith S. Currier, M.D., M.Sc. Lawrence Deyton, M.D., M.S.P.H. W. Lawrence Drew, M.D., Ph.D. William R. Duncan, Ph.D. Robert W. Eisinger, Ph.D. Wafaa El-Sadr, M.D., M.P.H., M.P.A. Judith Feinberg, M.D. Kenneth A. Freedberg, M.D., M.Sc. Hansjakob Furrer, M.D. John W. Gnann, Jr., M.D. Mark J. Goldberger, M.D., M.P.H. Sue Goldie, M.D., Ph.D. Eric P. Goosby, M.D. Peter A. Gross, M.D. Richard Hafner, M.D. Diane Havlir, M.D. Thomas M. Hooton, M.D. Douglas A. Jabs, M.D. Mark A. Jacobson, M.D. Edward Janoff, M.D. Mari Kitahata, M.D., Ph.D., Joseph V. Kovacs, M.D. Catherine Leport, M.D. Myron J. Levin, M.D. Juan C. Lopez, M.D. Michael Marco Douglas L. Mayers, M.D. David A. Melnick, M.D. Lynne M. Mofenson, M.D. Julio S.G. Montaner, M.D. Richard Moore, M.D. James Neaton, Ph.D. Charles Nelson Joseph F. O'Neill, M.D., M.S., M.P.H. Joel Palefsky, M.D. Alice Pau, Pharm.D. John P. Phair, M.D. Stephen Piscitelli, Pharm.D. Michael A. Polis, M.D., M.P.H. Thomas C. Quinn, M.D. Peter Reiss, M.D., Ph.D. David Rimland, M.D. Cynthia L. Sears, M.D. Leonard Seeff, M.D. Kent A. Sepkowitz, M.D. Thomas G. Slama, M.D. Elaine M. Sloand, M.D. Stephen A. Spector, M.D. David L. Thomas, M.D., M.P.H. Russell B. Van Dyke, M.D. D. Heather Watts, M.D. L. Joseph Wheat, M.D. Scott M. Whitcup, M.D. Paige Williams, Ph.D. Thomas C. Wright, Jr., M.D. CDC PARTICIPANTS Kenneth G. Castro, M.D. The following CDC staff member prepared this report: Jonathan E. Kaplan, M.D. in collaboration with Henry Masur, M.D. King K. Holmes, M.D., Ph.D. PREFACE In 1995, the U.S. Public Health Service (USPHS) and the Infectious Diseases Society of America (IDSA) developed guidelines for preventing opportunistic infections (OIs) in persons infected with human immunodeficiency virus (HIV) (1-3). These guidelines, written for health-care providers and patients, were revised in 1997 and published in the MMWR (4), Clinical Infectious Diseases (5), the Annals of Internal Medicine (6), the American Family Physician (7), and Pediatrics (8); an accompanying editorial appeared in JAMA (9). Response to these guidelines (e.g., the many requests for reprints and observations from health-care providers) suggests they have served as a valuable reference for HIV care providers. Because the 1995 and 1997 guidelines included ratings indicating the strength of each recommendation and the quality of supporting evidence, readers were able to assess the relative importance of each recommendation. Since AIDS was first recognized nearly 20 years ago, remarkable progress has been made in improving the quality and duration of life of HIV-infected persons. During the first decade of the epidemic, this improvement occurred because of better recognition of opportunistic disease processes, better therapy for acute and chronic complications, and the introduction of chemoprophylaxis against Pneumocystis carinii pneumonia (PCP), toxoplasmosis, Mycobacterium avium complex disease, and bacterial infections. Trimethoprim-sulfamethoxazole was shown to reduce not only the incidence of PCP but also of toxoplasmosis and bacterial infections. The second decade of the epidemic has witnessed extraordinary progress in developing highly active antiretroviral therapies (HAART) as well as continuing progress in preventing and treating individual OIs. HAART has reduced the incidence of OIs and extended life substantially (10). HAART is the most effective approach to preventing OIs and should be considered for all HIV-infected persons who qualify for such therapy. However, some patients are not ready or able to take HAART, and others have tried HAART regimens, but therapy has failed. Such patients will benefit from prophylaxis against OIs. In addition, prophylaxis against specific OIs continues to provide survival benefits even among persons who are receiving HAART (11). Because important new data concerning the prevention of opportunistic diseases have emerged since 1997, the USPHS and the IDSA reconvened the Prevention of Opportunistic Infections Working Group on March 4 and 5, 1999, to determine which recommendations warranted revision. Participants included representatives from federal agencies, universities, and professional societies, as well as community health-care providers and patient advocates. Much attention was focused on recent data related to the advisability of discontinuing OI prophylaxis (primary prophylaxis and prophylaxis against recurrence) among persons whose CD4+ T-lymphocyte counts have increased to above prophylaxis thresholds because of HAART. The OI Working Group also addressed two pathogens not previously considered -- human herpesvirus type 8 and hepatitis C virus. In addition, working group members reviewed data concerning the prevention of all common HIV-associated OIs. In revising these current guidelines, as in earlier editions of the guidelines, the group considered factors such as incidence of disease; severity of disease in terms of morbidity and mortality; level of immunosuppression at which disease is most likely to occur; feasibility, efficacy, and cost of preventive measures; impact of intervention on quality of life; and drug toxicities, drug interactions, and the potential for drug resistance to develop. During the development of these revised guidelines, working group members reviewed published manuscripts as well as abstracts and material presented at professional meetings if complete manuscripts providing data were available for review. A review of the data that served as the basis for the revisions and additional information discussed at the meeting but not deemed sufficient to justify a revision of the recommendations will be published separately in Clinical Infectious Diseases. Primary Changes in the Recommendations Primary changes in the disease-specific recommendations that follow include
These guidelines developed by the OI Working Group were made available for public comment through announcements in the Federal Register and the MMWR. The final document is endorsed by the USPHS and IDSA as well as by the Infectious Diseases Society of Obstetrics and Gynecology and the National Foundation for Infectious Diseases. How to Use the Information in This Report For each of the 19 diseases covered in this report, specific recommendations are provided that address a) prevention of exposure to the opportunistic pathogen, b) prevention of the first episode of disease, and c) prevention of disease recurrence. Recommendations are rated by a revised version of the IDSA rating system (see Box) (12). In this system, the letters A through E signify the strength of the recommendation for or against a preventive modality, and Roman numerals I through III indicate the quality of evidence supporting the recommendation. Because of their length and complexity, the tables in this report are grouped together, following the references. The tables appear in the following order: dosages for prophylaxis to prevent first episode of opportunistic disease in HIV-infected adults and adolescents (Table 1); dosages for prophylaxis to prevent recurrence of opportunistic disease in HIV-infected adults and adolescents (Table 2); effects of food on drugs used to treat OIs (Table 3); effects of medications on drugs used to treat OIs (Table 4); effects of OI medications on drugs commonly administered to HIV-infected persons (Table 5); adverse effects of drugs used to manage HIV infection (Table 6); dosages of drugs for prevention of OIs for persons with renal insufficiency (Table 7); costs of agents recommended for the prevention of OIs in adults with HIV infection (Table 8); immunologic categories for HIV-infected children (Table 9); immunization schedule for HIV-infected children (Table 10); dosages for prophylaxis to prevent first episode of opportunistic disease in HIV-infected infants and children (Table 11); dosages for prophylaxis to prevent recurrence of opportunistic disease in HIV-infected infants and children (Table 12); and criteria for discontinuing and restarting OI prophylaxis for adult patients with HIV infection (Table 13). Recommendations advising patients how to prevent exposure to opportunistic pathogens appear in the appendix at the end of this report. This report is oriented toward the prevention of specific opportunistic infections in HIV-infected persons in the United States and other industrialized countries. Recommendations for use of antiretroviral therapy, which is designed to prevent immunologic deterioration and delay the need for many of the chemoprophylactic strategies described in this report, are published elsewhere (10) as are integrated approaches to the care of HIV-infected persons (13). Single copies of this report can be obtained from the AIDS Treatment Information Service (ATIS) by calling (800) 448-0440, (301) 217-0023 (international), or (800) 243-7012 (TTY), and the report can be downloaded from the ATIS website at <www.hivatis.org>. In addition, pamphlets for patients are available from ATIS and also can be accessed on CDC's Division of HIV/AIDS Prevention homepage at <www.cdc.gov/hiv>. New data on prevention of OIs in HIV-infected persons are emerging, and randomized controlled trials addressing some unresolved issues in OI prophylaxis are ongoing. The OI Working Group has therefore developed a mechanism for routinely and periodically reviewing emerging data and for updating these guidelines on a regular basis. The most recent information will be available from the ATIS website at <www.hivatis.org>. DISEASE-SPECIFIC RECOMMENDATIONS Pneumocystis carinii Pneumonia Prevention of Exposure 1. Although some authorities recommend that persons with human immunodeficiency virus (HIV) infection who are at risk for P. carinii pneumonia (PCP) not share a hospital room with a patient who has PCP, data are insufficient to support this recommendation as standard practice (CIII). Prevention of Disease Initiation of Primary Prophylaxis 2. Adults and adolescents who have HIV infection (including pregnant women and those on HAART) should receive chemoprophylaxis against PCP if they have a CD4+ T-lymphocyte count of less than 200/µL (AI) or a history of oropharyngeal candidiasis (AII) (14). Persons who have a CD4+ T-lymphocyte percentage of less than 14% or history of an acquired immunodeficiency syndrome (AIDS)-defining illness but do not otherwise qualify should be considered for prophylaxis (BII) (15,16). When monitoring the CD4+ T-lymphocyte count at least every 3 months is not possible, initiation of chemoprophylaxis at a CD4+ T-lymphocyte count of greater than 200 but less than 250 cells/µL also should be considered (BII) (15). 3. Trimethoprim-sulfamethoxazole (TMP-SMZ) is the recommended prophylactic agent (AI) (16-18). One double-strength tablet per day is the preferred regimen (AI) (17). However, one single-strength tablet per day (19) is also effective and might be better tolerated (AI). One double-strength tablet three times per week is also effective (BI) (20). TMP-SMZ at a dose of one double-strength tablet per day confers cross-protection against toxoplasmosis (21) and some common respiratory bacterial infections (17,22). Lower doses of TMP-SMZ also might confer such protection. For patients who have an adverse reaction that is not life-threatening, treatment with TMP-SMZ should be continued if clinically feasible; for those who have discontinued such therapy because of an adverse reaction, reinstitution of TMP-SMZ should be strongly considered after the adverse event has resolved (AII). Patients who have experienced adverse events, especially fever and rash, might better tolerate reintroduction of the drug with a gradual increase in dose (desensitization) as per published regimens (BI) (23,24) or reintroduction of TMP-SMZ at a reduced dose or frequency (CIII); up to 70% of patients can tolerate such reinstitution of therapy (22). 4. If TMP-SMZ cannot be tolerated, prophylactic regimens that can be recommended as alternatives include dapsone (BI) (17), dapsone plus pyrimethamine plus leucovorin (BI) (25,26), aerosolized pentamidine administered by the Respirgard IITM nebulizer (Marquest, Englewood, Colorado) (BI) (18), and atovaquone (BI) (27,28). Atovaquone appears to be as effective as aerosolized pentamidine (28) or dapsone (BI) (27) but is substantially more expensive than the other regimens. For patients seropositive for Toxoplasma gondii who cannot tolerate TMP-SMZ, recommended alternatives to TMP-SMZ for prophylaxis against both PCP and toxoplasmosis include dapsone plus pyrimethamine (BI) (25,26) or atovaquone with or without pyrimethamine (CIII). The following regimens generally cannot be recommended as alternatives because data regarding their efficacy for PCP prophylaxis are insufficient for a firm recommendation: aerosolized pentamidine administered by other nebulization devices, intermittently administered parenteral pentamidine, oral pyrimethamine plus sulfadoxine, oral clindamycin plus primaquine, and intravenous trimetrexate. However, clinicians may consider using these agents in unusual situations in which the recommended agents cannot be administered (CIII). Discontinuation of Primary Prophylaxis 5. Initial reports from three prospective observational studies (29-31), one retrospective review (32), and one randomized trial (33) suggest that PCP prophylaxis can be safely discontinued in patients responding to HAART with a sustained increase in CD4+ T-lymphocyte counts from less than 200 cells/µL to greater than 200 cells/µL. Such reports have mostly included patients receiving primary prophylaxis (no prior episode of PCP) and protease inhibitor-containing regimens. In these studies, median follow-up ranged from 6 to 12 months and the median CD4+ T-lymphocyte count at the time prophylaxis was discontinued was greater than 300 cell/µL. At the time PCP prophylaxis was discontinued, many patients had sustained suppression of HIV plasma RNA levels below detection limits of the available assays. Although optimal criteria for discontinuing PCP prophylaxis are still being assessed, providers may wish to discontinue prophylaxis when patients have sustained a CD4+ T-lymphocyte count of greater than 200 cells/µL for at least 3-6 months (CII). Additional criteria might include sustained reduction in viral load for at least 3-6 months (CIII). Restarting Primary Prophylaxis 6. No data are available to guide recommendations for reinstituting primary prophylaxis. Pending the availability of such data, a reasonable approach would be to use the criteria for initiating prophylaxis described on page 5 (CIII). Prevention of Recurrence 7. Adults and adolescents who have a history of PCP should be administered chemoprophylaxis (i.e., secondary prophylaxis or chronic maintenance therapy) with the regimens described on page 5 in order to prevent recurrence (AI) (16). Discontinuation of Secondary Prophylaxis (Chronic Maintenance Therapy) 8. Although patients receiving secondary prophylaxis (prior episode of PCP) might also be at low risk for PCP when their CD4+ T-lymphocyte counts increase to greater than 200 cells/µL, inadequate numbers of patients have been evaluated to warrant a recommendation to discontinue prophylaxis in such patients. Special Considerations Children 9. Children born to HIV-infected mothers should be administered prophylaxis with TMP-SMZ beginning at 4-6 weeks of age (34) (AII). Prophylaxis should be discontinued for children who are subsequently found not to be infected with HIV. HIV-infected children and children whose infection status remains unknown should continue to receive prophylaxis for the first year of life. The need for subsequent prophylaxis should be determined on the basis of age-specific CD4+ T-lymphocyte count thresholds (Table 11) (AII). The safety of discontinuing prophylaxis in HIV-infected children receiving HAART has not been studied. 10. Children who have a history of PCP should be administered lifelong chemoprophylaxis to prevent recurrence (AI) (34). Pregnant Women 11. Chemoprophylaxis for PCP should be administered to pregnant women as is done for other adults and adolescents (AIII). TMP-SMZ is the recommended prophylactic agent; dapsone is an alternative. Because of theoretical concerns regarding possible teratogenicity associated with drug exposures during the first trimester, providers may choose to withhold prophylaxis during the first trimester. In such cases, aerosolized pentamidine may be considered because of its lack of systemic absorption and the resultant lack of exposure of the developing embryo to the drug (CIII). Toxoplasmic Encephalitis Prevention of Exposure 1. HIV-infected persons should be tested for immunoglobulin G (IgG) antibody to Toxoplasma soon after the diagnosis of HIV infection to detect latent infection with Toxoplasma gondii (BIII). 2. All HIV-infected persons, but particularly those who lack IgG antibody to Toxoplasma, should be counseled about the various sources of toxoplasmic infection. They should be advised not to eat raw or undercooked meat, particularly undercooked pork, lamb, or venison (BIII). Specifically, meat should be cooked to an internal temperature of 150 F (65.5 C); meat cooked until it is no longer pink inside generally has an internal temperature of 165 F (73.8 C) and therefore satisfies this requirement. HIV-infected persons should wash their hands after contact with raw meat and after gardening or other contact with soil; in addition, they should wash fruits and vegetables well before eating them raw (BIII). If the patient owns a cat, the litter box should be changed daily, preferably by an HIV-negative, nonpregnant person; alternatively, the patient should wash the hands thoroughly after changing the litter box (BIII). Patients should be encouraged to keep their cats inside and not to adopt or handle stray cats (BIII). Cats should be fed only canned or dried commercial food or well-cooked table food, not raw or undercooked meats (BIII). Patients need not be advised to part with their cats or to have their cats tested for toxoplasmosis (EII). Prevention of Disease Initiation of Primary Prophylaxis 3. Toxoplasma-seropositive patients who have a CD4+ T-lymphocyte count of less than 100/µL should be administered prophylaxis against toxoplasmic encephalitis (TE) (AII) (21). The double-strength tablet daily dose of TMP-SMZ recommended as the preferred regimen for PCP prophylaxis appears to be effective against TE as well and is therefore recommended (AII) (21). If patients cannot tolerate TMP-SMZ, the recommended alternative is dapsone-pyrimethamine, which is also effective against PCP (BI) (25,26). Atovaquone with or without pyrimethamine also may be considered (CIII). Prophylactic monotherapy with dapsone, pyrimethamine, azithromycin, or clarithromycin cannot be recommended on the basis of current data (DII). Aerosolized pentamidine does not protect against TE and is not recommended (EI) (17,21). 4. Toxoplasma-seronegative persons who are not taking a PCP prophylactic regimen known to be active against TE should be retested for IgG antibody to Toxoplasma when their CD4+ T-lymphocyte count declines below 100/µL to determine whether they have seroconverted and are therefore at risk for TE (CIII). Patients who have seroconverted should be administered prophylaxis for TE as described above (AII). Discontinuation of Primary Prophylaxis 5. Limited data suggest that discontinuing prophylaxis for patients whose CD4+ T-lymphocyte counts increase to greater than 100 cells/µL in response to HAART is associated with a low risk for TE. However, the numbers of patients who have been evaluated are insufficient to recommend routine discontinuation of prophylaxis in such patients. Persons whose CD4+ T-lymphocyte count remains less than 200 cells/µL or who have a history of PCP or oropharyngeal candidiasis still require prophylaxis against PCP, as noted previously. Prevention of Recurrence 6. Patients who have had TE should be administered lifelong suppressive therapy (secondary prophylaxis or chronic maintenance therapy) with drugs active against Toxoplasma to prevent relapse (AI) (35,36). The combination of pyrimethamine plus sulfadiazine and leucovorin is highly effective for this purpose (AI) (35,36). A commonly used regimen for patients who cannot tolerate sulfa drugs is pyrimethamine plus clindamycin (BI); however, only the combination of pyrimethamine plus sulfadiazine appears to provide protection against PCP as well (AII). Discontinuation of Secondary Prophylaxis (Chronic Maintenance Therapy) 7. The numbers of patients who have stopped maintenance therapy after responding to HAART are insufficient to warrant recommending discontinuation of maintenance therapy. Special Considerations Children 8. TMP-SMZ, when administered for PCP prophylaxis, also provides prophylaxis against toxoplasmosis. Atovaquone might also provide protection (CIII). Children aged greater than 12 months who qualify for PCP prophylaxis and who are receiving an agent other than TMP-SMZ or atovaquone should have serologic testing for Toxoplasma antibody (BIII), because alternative drugs for PCP prophylaxis might not be effective against Toxoplasma. Severely immunosuppressed children who are not receiving TMP-SMZ or atovaquone who are found to be seropositive for Toxoplasma should be administered prophylaxis for both PCP and toxoplasmosis (i.e., dapsone plus pyrimethamine) (BIII). Pregnant Women 9. TMP-SMZ can be administered for prophylaxis against TE as described for PCP (AIII). However, because of the low incidence of TE during pregnancy and the possible risk associated with pyrimethamine treatment, chemoprophylaxis with pyrimethamine-containing regimens can reasonably be deferred until after pregnancy (CIII). For prophylaxis against recurrent TE, the health-care provider and clinician should be well informed about the benefit of lifelong therapy and the concerns about teratogenicity of pyrimethamine. Most clinicians favor lifelong therapy for the mother, given the high likelihood that disease will recur promptly if therapy is stopped (AIII). 10. In rare cases, HIV-infected pregnant women who have serologic evidence of remote toxoplasmic infection have transmitted Toxoplasma to the fetus in utero. Pregnant HIV-infected women who have evidence of primary toxoplasmic infection or active toxoplasmosis (including TE) should be evaluated and managed during pregnancy in consultation with appropriate specialists (BIII). Infants born to women who have serologic evidence of infections with HIV and Toxoplasma should be evaluated for congenital toxoplasmosis (BIII). Cryptosporidiosis Prevention of Exposure 1. HIV-infected persons should be educated and counseled about the many ways that Cryptosporidium can be transmitted (BIII). Modes of transmission include having direct contact with infected adults, diaper-aged children, and infected animals; drinking contaminated water; coming into contact with contaminated water during recreational activities; and eating contaminated food. 2. HIV-infected persons should avoid contact with human and animal feces. They should be advised to wash their hands after contact with human feces (e.g., diaper changing), after handling pets, and after gardening or other contact with soil. HIV-infected persons should avoid sexual practices that might result in oral exposure to feces (e.g., oral-anal contact) (BIII). 3. HIV-infected persons should be advised that newborn and very young pets might pose a small risk for transmitting cryptosporidial infection, but they should not be advised to destroy or give away healthy pets. Persons contemplating the acquisition of a new pet should avoid bringing any animal that has diarrhea into their households, should avoid purchasing a dog or cat aged less than 6 months, and should not adopt stray pets. HIV-infected persons who wish to assume the small risk for acquiring a puppy or kitten aged less than 6 months should request that their veterinarian examine the animal's stool for Cryptosporidium before they have contact with the animal (BIII). 4. HIV-infected persons should avoid exposure to calves and lambs and to premises where these animals are raised (BII). 5. HIV-infected persons should not drink water directly from lakes or rivers (AIII). 6. Waterborne infection also might result from swallowing water during recreational activities. HIV-infected persons should be aware that many lakes, rivers, and salt-water beaches and some swimming pools, recreational water parks, and ornamental water fountains might be contaminated with human or animal waste that contains Cryptosporidium. They should avoid swimming in water that is likely to be contaminated and should avoid swallowing water while swimming or playing in recreational waters (BIII). 7. Several outbreaks of cryptosporidiosis have been linked to municipal water supplies. During outbreaks or in other situations in which a community "boil-water" advisory is issued, boiling water for 1 minute will eliminate the risk for cryptosporidiosis (AI). Use of submicron personal-use water filters* (home/office types) and/or bottled water** also might reduce the risk (CIII). The magnitude of the risk for acquiring cryptosporidiosis from drinking water in a nonoutbreak setting is uncertain, and current data are inadequate to recommend that all HIV-infected persons boil water or avoid drinking tap water in nonoutbreak settings. However, HIV-infected persons who wish to take independent action to reduce the risk for waterborne cryptosporidiosis may choose to take precautions similar to those recommended during outbreaks. Such decisions should be made in conjunction with health-care providers. Persons who opt for a personal-use filter or bottled water should be aware of the complexities involved in selecting appropriate products, the lack of enforceable standards for the destruction or removal of oocysts, the cost of the products, and the logistic difficulty of using these products consistently. 8. Patients who take precautions to avoid acquiring cryptosporidiosis from drinking water should be advised that ice made from contaminated tap water also can be a source of infection (BII). Such persons also should be aware that fountain beverages served in restaurants, bars, theaters, and other places also might pose a risk because these beverages, as well as the ice they contain, are made from tap water. Nationally distributed brands of bottled or canned carbonated soft drinks are safe to drink. Commercially packaged noncarbonated soft drinks and fruit juices that do not require refrigeration until after they are opened (i.e., those that can be stored unrefrigerated on grocery shelves) also are safe. Nationally distributed brands of frozen fruit juice concentrate are safe if they are reconstituted by the user with water from a safe source. Fruit juices that must be kept refrigerated from the time they are processed to the time of consumption might be either fresh (unpasteurized) or heat-treated (pasteurized); only those juices labeled as pasteurized should be considered free of risk from Cryptosporidium. Other pasteurized beverages and beers also are considered safe to drink (BII). No data are available concerning survival of Cryptosporidium oocysts in wine. 9. HIV-infected persons should avoid eating raw oysters because cryptosporidial oocysts can survive in oysters for more than 2 months and have been found in oysters taken from some commercial oyster beds (BIII). Cryptosporidium-infected patients should not work as food handlers, especially if the food to be handled is intended to be eaten without cooking (BII). Because most foodborne outbreaks of cryptosporidiosis are believed to have been caused by infected food handlers, more specific recommendations to avoid exposure to contaminated food cannot be made. 10. In a hospital, standard precautions (i.e., use of gloves and hand washing after removal of gloves) should be sufficient to prevent transmission of cryptosporidiosis from an infected patient to a susceptible HIV-infected person (BII). However, because of the potential for fomite transmission, some experts recommend that HIV-infected persons, especially those who are severely immunocompromised, should not share a room with a patient with cryptosporidiosis (CIII). Prevention of Disease 11. No agents have been proven to be effective as chemoprophylaxis against cryptosporidiosis. Rifabutin or clarithromycin, when taken for Mycobacterium avium complex prophylaxis, were associated with a reduced risk for cryptosporidiosis in one study (37), but data are insufficient to warrant a recommendation for using these drugs. Prevention of Recurrence 12. No drug regimens are known to be effective in preventing the recurrence of cryptosporidiosis. Special Considerations Children 13. At present, no data indicate that formula-preparation practices for infants should be altered in an effort to prevent cryptosporidiosis (CIII). However, in the event of a "boil-water" advisory, similar precautions for the preparation of infant formula should be taken as for drinking water for adults (AII). Microsporidiosis Prevention of Exposure 1. Other than general attention to hand washing and other personal hygiene measures, no precautions to reduce exposure can be recommended at this time. Prevention of Disease 2. No chemoprophylactic regimens are known to be effective in preventing microsporidiosis. Prevention of Recurrence 3. No chemotherapeutic regimens are known to be effective in preventing the recurrence of microsporidiosis. Tuberculosis Prevention of Exposure 1. HIV-infected persons should be advised that certain activities and occupations might increase the likelihood of exposure to tuberculosis (BIII). These include volunteer work or employment in health-care facilities, correctional institutions, and shelters for the homeless, as well as in other settings identified as high risk by local health authorities. Decisions about whether to continue with activities in these settings should be made in conjunction with the health-care provider and should be based on factors such as the patient's specific duties in the workplace, the prevalence of tuberculosis in the community, and the degree to which precautions are taken to prevent the transmission of tuberculosis in the workplace (BIII). Whether the patient continues with such activities might affect the frequency with which screening for tuberculosis needs to be conducted. Prevention of Disease 2. When HIV infection is first recognized, the patient should receive a tuberculin skin test (TST) by administration of intermediate-strength (5-TU) purified protein derivative (PPD) by the Mantoux method (AI). Routine evaluation for anergy is not recommended. However, there are selected situations in which anergy evaluation might assist in guiding individual decisions about preventive therapy (38). 3. All HIV-infected persons who have a positive TST result (greater than or equal to 5 mm of induration) should undergo chest radiography and clinical evaluation to rule out active tuberculosis. HIV-infected persons who have symptoms suggestive of tuberculosis should promptly undergo chest radiography and clinical evaluation regardless of their TST status (AII). 4. All HIV-infected persons, regardless of age, who have a positive TST result yet have no evidence of active tuberculosis and no history of treatment or prophylaxis for tuberculosis should be administered preventive chemotherapy. Options include isoniazid daily (AII) or twice weekly (BI) for 9 months or 2 months of therapy with either rifampin and pyrazinamide (AI) or rifabutin and pyrazinamide (BIII) (38). Because HIV-infected persons are at risk for peripheral neuropathy, those receiving isoniazid should also receive pyridoxine (BIII). A decision to use a regimen containing either rifampin or rifabutin should be made after careful consideration of potential drug interactions, especially those related to protease inhibitors and nonnucleoside reverse transcriptase inhibitors (see Special Considerations/Drug Interactions, page 13). Directly observed therapy should be used with intermittent dosing regimens (AI) and when otherwise operationally feasible (BIII) (38). 5. HIV-infected persons who are close contacts of persons who have infectious tuberculosis should be administered preventive therapy -- regardless of their TST results, age, or prior courses of chemoprophylaxis -- after the diagnosis of active tuberculosis has been excluded (AII) (38). In addition to household contacts, such persons might also include contacts in the same drug-treatment or health-care facility, coworkers, and other contacts if transmission of TB is demonstrated. 6. For persons exposed to isoniazid- and/or rifampin-resistant TB, the decision to use chemoprophylactic antimycobacterial agents other than isoniazid alone, rifampin plus pyrazinamide, or rifabutin plus pyrazinamide should be based on the relative risk for exposure to resistant organisms and should be made in consultation with public health authorities (AII). 7. TST-negative, HIV-infected persons from risk groups or geographic areas with a high prevalence of Mycobacterium tuberculosis infection might be at increased risk for primary or reactivation tuberculosis. However, the efficacy of preventive therapy in this group has not been demonstrated. Decisions concerning the use of chemoprophylaxis in these situations must be considered individually. 8. Although the reliability of the TST might diminish as the CD4+ T-lymphocyte count declines, annual repeat testing should be considered for HIV-infected persons who are TST-negative on initial evaluation and who belong to populations in which there is a substantial risk for exposure to M. tuberculosis (BIII). Clinicians also may consider repeating TSTs for persons whose immune function has improved because of HAART (i.e., those whose CD4+ T-lymphocyte count has increased to greater than 200 cells/µL) (CIII). In addition to confirming tuberculous infection, TST conversion in an HIV-infected person should alert health-care providers to the possibility of recent M. tuberculosis transmission and should prompt notification of public health officials for investigation to identify a possible source case. 9. The administration of bacille Calmette-Guerin (BCG) vaccine to HIV-infected persons is contraindicated because of its potential to cause disseminated disease (EII). Prevention of Recurrence 10. Chronic suppressive therapy for a patient who has successfully completed a recommended regimen of treatment for tuberculosis is not necessary (DII). Special Considerations Drug Interactions 11. Rifampin should not be administered with protease inhibitors or nonnucleoside reverse transcriptase inhibitors (EI) (38). Rifabutin is an acceptable alternative but should not be used with the protease inhibitor hard-gel saquinavir; caution is also advised if the drug is coadministered with soft-gel saquinavir, but data are lacking. Rifabutin can be administered at one half the usual daily dose (i.e., reduce from 300 mg to 150 mg per day) with indinavir, nelfinavir, or amprenavir or with one fourth the usual dose (i.e., 150 mg every other day or three times a week) with ritonavir. Similarly, rifabutin should not be used with the nonnucleoside reverse transcriptase inhibitor delavirdine. Pharmacokinetic data suggest that rifabutin at an increased dose can be administered with efavirenz; a dose of 450 mg per day has been suggested (38). Information is lacking regarding coadministration of rifabutin with nevirapine. Children 12. Infants born to HIV-infected mothers should have a TST (5-TU PPD) at or before the age of 9-12 months and should be retested at least once a year (AIII). HIV-infected children living in households with TST-positive persons should be evaluated for tuberculosis (AIII); children exposed to a person who has active tuberculosis should be administered preventive therapy after active tuberculosis has been excluded, regardless of their TST results (AII). Pregnant Women 13. Chemoprophylaxis for tuberculosis is recommended during pregnancy for HIV-infected patients who have either a positive TST or a history of exposure to active tuberculosis, after active tuberculosis has been excluded (AIII). A chest radiograph should be obtained before treatment and appropriate abdominal/pelvic lead apron shields should be used to minimize radiation exposure to the embryo/fetus. When an HIV-infected person has not been exposed to drug-resistant TB, isoniazid daily or twice weekly is the prophylactic regimen of choice. Because of concerns regarding possible teratogenicity associated with drug exposures during the first trimester, providers may choose to initiate prophylaxis after the first trimester. Preventive therapy with isoniazid should be accompanied by pyridoxine to reduce the risk for neurotoxicity. Experience with rifampin or rifabutin during pregnancy is more limited, but anecdotal experience with rifampin has not been associated with adverse pregnancy outcomes. Pyrazinamide should generally be avoided, particularly in the first trimester because of lack of information concerning fetal effects. Disseminated Infection with Mycobacterium avium Complex Prevention of Exposure 1. Organisms of the M. avium complex (MAC) are common in environmental sources such as food and water. Current information does not support specific recommendations regarding avoidance of exposure. Prevention of Disease Initiation of Primary Prophylaxis 2. Adults and adolescents who have HIV infection should receive chemoprophylaxis against disseminated MAC disease if they have a CD4+ T-lymphocyte count of less than 50 cells/µL (AI) (4). Clarithromycin (39,40) or azithromycin (41) are the preferred prophylactic agents (AI). The combination of clarithromycin and rifabutin is no more effective than clarithromycin alone for chemoprophylaxis and is associated with a higher rate of adverse effects than either drug alone; this combination should not be used (EI) (39). The combination of azithromycin with rifabutin is more effective than azithromycin alone; however, the additional cost, increased occurrence of adverse effects, potential for drug interactions, and absence of a difference in survival when compared with azithromycin alone do not warrant a routine recommendation for this regimen (CI) (41). In addition to their preventive activity for MAC disease, clarithromycin and azithromycin each confer protection against respiratory bacterial infections (BII). If clarithromycin or azithromycin cannot be tolerated, rifabutin is an alternative prophylactic agent for MAC disease (BI) (39,41,42). Tolerance, cost, and drug interactions are among the issues that should be considered in decisions regarding the choice of prophylactic agents for MAC disease. Particular attention to interactions with antiretroviral protease inhibitors and nonnucleoside reverse transcriptase inhibitors is warranted (see Special Considerations/Drug Interactions, page 15). Before prophylaxis is initiated, disseminated MAC disease should be ruled out by clinical assessment, which might include obtaining a blood culture for MAC if warranted. Because treatment with rifabutin could result in the development of resistance to rifampin in persons who have active tuberculosis, active tuberculosis should also be excluded before rifabutin is used for prophylaxis. 3. Although the detection of MAC organisms in the respiratory or gastrointestinal tract might predict the development of disseminated MAC infection, no data are available on the efficacy of prophylaxis with clarithromycin, azithromycin, rifabutin, or other drugs in patients with MAC organisms at these sites and a negative blood culture. Therefore, routine screening of respiratory or gastrointestinal specimens for MAC cannot be recommended (DIII). Discontinuation of Primary Prophylaxis 4. Information from observational studies suggested a low rate of disseminated infection with MAC among persons who responded to HAART with an increase in CD4+ T-lymphocyte count from less than 50 cells/µL to greater than 100 cells/µL (32,43). Although the optimal criteria for discontinuing MAC prophylaxis remain to be defined, a reasonable option would be to consider discontinuing prophylaxis in patients with a CD4+ T-lymphocyte count of greater than 100 cells/µL for a sustained period (e.g., greater than 3-6 months) and sustained suppression of HIV plasma RNA for a similar period (CII). Restarting Primary Prophylaxis 5. No data are available on which to base recommendations for reinstituting prophylaxis. Pending the availability of such data, a reasonable approach would be to use the criteria for initiating prophylaxis described on page 14 (CIII). Prevention of Recurrence 6. Patients who have been treated for disseminated MAC disease should continue to receive full therapeutic doses of antimycobacterial agents for life (i.e., secondary prophylaxis or chronic maintenance therapy) (AII) (42). Unless good clinical or laboratory evidence of macrolide resistance exists, the use of a macrolide (clarithromycin or, alternatively, azithromycin) is recommended in combination with ethambutol (AII) with or without rifabutin (CI) (44,45). Treatment of MAC disease with clarithromycin in a dose of 1,000 mg twice a day is associated with a higher mortality rate than has been observed with clarithromycin administered at 500 mg twice a day; thus, the higher dose should not be used (EI) (46,47). Clofazimine has been associated with an adverse clinical outcome in the treatment of MAC disease and should not be used (DII) (47,48). Discontinuation of Secondary Prophylaxis (Chronic Maintenance Therapy) 7. Although patients receiving chronic maintenance therapy for MAC might be at low risk for recurrence of MAC when their CD4+ T-lymphocyte counts increase to greater than 100 cells/µL following 6-12 months of HAART, the numbers of patients who have been evaluated are insufficient to warrant a recommendation to discontinue maintenance therapy in such patients. Special Considerations Drug Interactions 8. Rifabutin should not be administered with certain protease inhibitors or nonnucleoside reverse transcriptase inhibitors (see Special Considerations/Drug Interactions in Tuberculosis section, page 13). Although protease inhibitors might also increase clarithromycin levels, no recommendation to adjust the dose of either clarithromycin or protease inhibitors can be made on the basis of existing data. Children 9. HIV-infected children aged less than 13 years who have advanced immunosuppression also can develop disseminated MAC infections, and prophylaxis should be offered to high-risk children according to the following CD4+ T-lymphocyte thresholds: children aged greater than or equal to 6 years, less than 50 cells/µL; children aged 2-6 years, less than 75 cells/µL; children aged 1-2 years, less than 500 cells/µL; and children aged less than 12 months, less than 750 cells/µL (AII). For the same reasons that clarithromycin and azithromycin are the preferred prophylactic agents for adults, they should also be considered for children (AII); oral suspensions of both agents are commercially available in the United States. No liquid formulation of rifabutin suitable for pediatric use is commercially available in the United States. The safety of discontinuing MAC prophylaxis in children whose CD4+ T-lymphocyte counts have increased in response to HAART has not been studied. Pregnant Women 10. Chemoprophylaxis for MAC disease should be administered to pregnant women as is done for other adults and adolescents (AIII). However, because of general concerns about administering drugs during the first trimester of pregnancy, some providers may choose to withhold prophylaxis during the first trimester. Animal studies and anecdotal evidence of safety in humans suggest that of the available agents, azithromycin is the drug of choice (BIII) (49). Experience with rifabutin is limited. Clarithromycin has been demonstrated to be a teratogen in animals and should be used with caution during pregnancy (50). For secondary prophylaxis (chronic maintenance therapy), azithromycin plus ethambutol are the preferred drugs (BIII). Bacterial Respiratory Infections Prevention of Exposure 1. Because Streptococcus pneumoniae and Haemophilus influenzae are common in the community, no effective way exists to reduce exposure to these bacteria. Prevention of Disease 2. As soon as feasible after HIV infection is diagnosed, adults and adolescents who have a CD4+ T-lymphocyte count of greater than or equal to 200 cells/µL should be administered a single dose of 23-valent polysaccharide pneumococcal vaccine if they have not had this vaccine during the previous 5 years (BII) (51,52). For persons who have a CD4+ T-lymphocyte count of less than 200 cells/µL, vaccination can be offered, although the humoral response and clinical efficacy are likely to be diminished (CIII). The recommendation to vaccinate is increasingly pertinent because of the increasing incidence of invasive infections with drug-resistant (including TMP-SMZ-, macrolide-, penicillin-, and beta-lactam-resistant) strains of S. pneumoniae. Limited data suggest that administration of certain bacterial vaccines might transiently increase HIV replication and plasma HIV-1 RNA levels in a minority of HIV-infected persons. However, there is no evidence that adverse clinical outcomes are associated with this transient increase. Most experts believe that the benefit of pneumococcal vaccination outweighs the potential risk. 3. The duration of the protective effect of primary pneumococcal vaccination is unknown. Periodic revaccination may be considered; an interval of 5 years has been recommended for persons not infected with HIV and also might be appropriate for persons infected with HIV (53). In addition, revaccination one time should also be considered if the initial vaccination was given when the CD4+ T-lymphocyte count was less than 200 cells/µL and if the CD4+ T-lymphocyte count has increased to greater than 200 cells/µL as a result of HAART (CIII). 4. The incidence of H. influenzae type B infection in adults is low. Therefore, H. influenzae type B vaccine is not generally recommended for adult use (DIII). 5. TMP-SMZ, when administered daily for PCP prophylaxis, reduces the frequency of bacterial respiratory infections; this should be considered in the selection of an agent for PCP prophylaxis (AII). However, indiscriminate use of this drug (when not indicated for PCP prophylaxis or other specific reasons) might promote the development of TMP-SMZ-resistant organisms. Thus, TMP-SMZ should not be prescribed solely to prevent bacterial respiratory infection (DIII). Similarly, clarithromycin administered daily and azithromycin administered weekly for MAC prophylaxis might be effective in preventing bacterial respiratory infections; this should be considered in the selection of an agent for prophylaxis against MAC disease (BII). However, these drugs should not be prescribed solely for preventing bacterial respiratory infection (DIII). 6. An absolute neutrophil count that is depressed because of HIV disease or drug therapy is associated with an increased risk for bacterial infections, including pneumonia. To reduce the risk for such bacterial infections, providers may consider taking steps to reverse neutropenia, either by stopping myelosuppressive drugs (CII) or by administering granulocyte-colony-stimulating factor (G-CSF) (CII). Prevention of Recurrence 7. Some clinicians may administer antibiotic chemoprophylaxis to HIV-infected patients who have very frequent recurrences of serious bacterial respiratory infections (CIII). TMP-SMZ, administered for PCP prophylaxis, and clarithromycin or azithromycin, administered for MAC prophylaxis, are appropriate for drug-sensitive organisms. However, providers should be cautious about using antibiotics solely for preventing the recurrence of serious bacterial respiratory infections because of the potential development of drug-resistant microorganisms and drug toxicity. Special Considerations Children 8. Children who have HIV infection should be administered H. influenzae type b vaccine in accordance with the guidelines of the Advisory Committee on Immunization Practices (54) and the American Academy of Pediatrics (55) (AII). Children aged greater than 2 years also should be administered 23-valent polysaccharide pneumococcal vaccine (BII). Revaccination with pneumococcal vaccine generally should be offered after 3-5 years to children aged less than 10 years and after 5 years to children aged greater than or equal to 10 years (BIII). 9. To prevent serious bacterial infections in HIV-infected children who have hypogammaglobulinemia (IgG less than 400 mg/dL), clinicians should use intravenous immunoglobulin (IVIG) (AI). Respiratory syncytial virus (RSV) IVIG (750 mg/kg), not monoclonal RSV antibody, may be substituted for IVIG during the RSV season to provide broad anti-infective protection, if RSV IVIG is available. 10. To prevent recurrence of serious bacterial respiratory infections, antibiotic chemoprophylaxis may be considered (BI). However, providers should be cautious about using antibiotics solely for this purpose because of the potential development of drug-resistant microorganisms and drug toxicity. The administration of IVIG should also be considered for HIV-infected children who have recurrent serious bacterial infections (BI), although such treatment might not provide additional benefit to children who are being administered daily TMP-SMZ. However, IVIG may be considered for children who have recurrent serious bacterial infections despite receiving TMP-SMZ or other antimicrobials (CIII). Pregnant Women 11. Pneumococcal vaccination is recommended during pregnancy for HIV-infected patients who have not been vaccinated during the previous 5 years (BIII). Among nonpregnant adults, vaccination has been associated with a transient burst of HIV replication. Whether the transient viremia can increase the risk for perinatal HIV transmission is unknown. Because of this concern, when feasible, vaccination may be deferred until after antiretroviral therapy has been initiated to prevent perinatal HIV transmission (CIII). Bacterial Enteric Infections Prevention of Exposure Food 1. Health-care providers should advise HIV-infected persons not to eat raw or undercooked eggs (including foods that might contain raw eggs [e.g., some preparations of hollandaise sauce, Caesar and other salad dressings, and mayonnaise]); raw or undercooked poultry, meat, or seafood; or unpasteurized dairy products. Poultry and meat should be well cooked and should not be pink in the middle (internal temperature greater than 165 F [73.8 C]). Produce should be washed thoroughly before being eaten (BIII). 2. Health-care providers should advise HIV-infected persons to avoid cross-contamination of foods. Uncooked meats should not come into contact with other foods. Hands, cutting boards, counters, knives, and other utensils should be washed thoroughly after contact with uncooked foods (BIII). 3. Health-care providers should advise HIV-infected persons that, although the incidence of listeriosis is low, it is a serious disease that occurs with unusually high frequency among HIV-infected persons who are severely immunosuppressed. Such persons may choose to avoid soft cheeses because some studies have shown an association between these foods and listeriosis. These studies also have documented an association between ready-to-eat foods (e.g., hot dogs and cold cuts from delicatessen counters) and listeriosis. An immunosuppressed, HIV-infected person who wishes to reduce the risk for foodborne disease as much as possible may choose to reheat such foods until they are steaming hot before eating them (CIII). Pets 4. When obtaining a new pet, HIV-infected persons should avoid animals aged less than 6 months, especially those that have diarrhea (BIII). 5. HIV-infected persons should avoid contact with animals that have diarrhea (BIII). HIV-infected pet owners should seek veterinary care for animals with diarrheal illness, and a fecal sample from such animals should be examined for Cryptosporidium, Salmonella, and Campylobacter. 6. HIV-infected persons should wash their hands after handling pets (especially before eating) and should avoid contact with pets' feces (BIII). 7. HIV-infected persons should avoid contact with reptiles (e.g., snakes, lizards, iguanas, and turtles) because of the risk for salmonellosis (BIII). Travel 8. The risk for foodborne and waterborne infections among immunosuppressed, HIV-infected persons is magnified during travel to developing countries. Persons who travel to such countries should avoid foods and beverages that might be contaminated, particularly raw fruits and vegetables, raw or undercooked seafood or meat, tap water, ice made with tap water, unpasteurized milk and dairy products, and items sold by street vendors (AII). Foods and beverages that are generally safe include steaming-hot foods, fruits that are peeled by the traveler, bottled (especially carbonated) beverages, hot coffee and tea, beer, wine, and water brought to a rolling boil for 1 minute (AII). Treatment of water with iodine or chlorine might not be as effective as boiling but can be used when boiling is not practical (BIII). Prevention of Disease 9. Prophylactic antimicrobial agents are not generally recommended for travelers (DIII). The effectiveness of these agents depends on local antimicrobial-resistance patterns of gastrointestinal pathogens, which are seldom known. Moreover, these agents can elicit adverse reactions and can promote the emergence of resistant organisms. However, for HIV-infected travelers, antimicrobial prophylaxis may be considered, depending on the level of immunosuppression and the region and duration of travel (CIII). The use of fluoroquinolones such as ciprofloxacin (500 mg per day) can be considered when prophylaxis is deemed necessary (BIII). As an alternative (e.g., for children, pregnant women, and persons already taking TMP-SMZ for PCP prophylaxis), TMP-SMZ might offer some protection against traveler's diarrhea (BIII). The risk of toxicity should be considered before treatment with TMP-SMZ is initiated solely because of travel. 10. Antimicrobial agents such as fluoroquinolones should be given to patients before their departure, to be taken empirically (e.g., 500 mg of ciprofloxacin twice a day for 3-7 days) should traveler's diarrhea develop (BIII). Fluoroquinolones should be avoided for children aged less than 18 years and pregnant women, and alternative antibiotics should be considered (BIII). Travelers should consult a physician if their diarrhea is severe and does not respond to empirical therapy, if their stools contain blood, if fever is accompanied by shaking chills, or if dehydration develops. Antiperistaltic agents (e.g., diphenoxylate and loperamide) can be used to treat mild diarrhea. However, the use of these drugs should be discontinued if symptoms persist beyond 48 hours. Moreover, these agents should not be administered to patients who have a high fever or who have blood in the stool (AII). 11. Some experts recommend that HIV-infected persons who have Salmonella gastroenteritis be administered antimicrobial therapy to prevent extraintestinal spread of the pathogen. However, no controlled study has demonstrated a beneficial effect of such treatment, and some studies of immunocompetent persons have suggested that antimicrobial therapy can lengthen the shedding period. The fluoroquinolones -- primarily ciprofloxacin (750 mg twice a day for 14 days) -- can be used when antimicrobial therapy is chosen (CIII). Prevention of Recurrence 12. HIV-infected persons who have Salmonella septicemia require long-term therapy (i.e., secondary prophylaxis or chronic maintenance therapy) to prevent recurrence. Fluoroquinolones, primarily ciprofloxacin, are usually the drugs of choice for susceptible organisms (BII). 13. Household contacts of HIV-infected persons who have salmonellosis or shigellosis should be evaluated for persistent asymptomatic carriage of Salmonella or Shigella so that strict hygienic measures and/or antimicrobial therapy can be instituted and recurrent transmission to the HIV-infected person can be prevented (CIII). Special Considerations Children 14. Like HIV-infected adults, HIV-infected children should wash their hands after handling pets (especially before eating) and should avoid contact with pets' feces. Hand washing should be supervised (BIII). 15. HIV-exposed infants aged less than 3 months and all HIV-infected children who have severe immunosuppression should be administered treatment for Salmonella gastroenteritis to prevent extraintestinal spread of the pathogen (CIII). Choices of antibiotics include TMP-SMZ, ampicillin, cefotaxime, ceftriaxone, or chloramphenicol; fluoroquinolones should be used with caution and only if no alternatives exist. 16. HIV-infected children who have Salmonella septicemia should be offered long-term therapy to prevent recurrence (CIII). TMP-SMZ is the drug of choice; ampicillin or chloramphenicol can be used if the organism is susceptible. Fluoroquinolones should be used with caution and only if no alternative exists. 17. Antiperistaltic drugs are not recommended for children (DIII). Pregnant Women 18. Because both pregnancy and HIV infection confer a risk for listeriosis, pregnant HIV-infected women should heed recommendations regarding listeriosis (BII). 19. Because extraintestinal spread of Salmonella during pregnancy might lead to infection of the placenta and amniotic fluid and result in pregnancy loss similar to that seen with Listeria monocytogenes, pregnant women with Salmonella gastroenteritis should receive treatment (BIII). Choices for treatment include ampicillin, cefotaxime, ceftriaxone, or TMP-SMZ. Fluoroquinolones should be avoided. 20. Fluoroquinolones should not be used during pregnancy. TMP-SMZ might offer some protection against traveler's diarrhea. Infection with Bartonella (Formerly Rochalimaea) Prevention of Exposure 1. HIV-infected persons, particularly those who are severely immunosuppressed, are at unusually high risk for developing relatively severe disease due to infection with Bartonella, which can be transmitted from cats. These persons should consider the potential risks of cat ownership (CIII). Persons who acquire a cat should adopt or purchase an animal aged greater than 1 year that is in good health (BII). 2. Although declawing is not generally advised, HIV-infected persons should avoid rough play with cats and situations in which scratches are likely (BII). Any cat-associated wound should be washed promptly (CIII). Cats should not be allowed to lick open wounds or cuts of HIV-infected persons (BIII). 3. Care of cats should include flea control (CIII). 4. No evidence indicates any benefits to cats or their owners from routine culture or serologic testing of the pet for Bartonella infection (DII). Prevention of Disease 5. No data support chemoprophylaxis for Bartonella-associated disease (CIII). Prevention of Recurrence 6. Relapse or reinfection with Bartonella has sometimes followed a course of primary treatment. Although no firm recommendation can be made regarding prophylaxis in this situation, long-term suppression of infection with erythromycin or doxycycline should be considered (CIII). Special Considerations Children 7. The risks of cat ownership for HIV-infected children who are severely immunocompromised should be discussed with parents and caretakers (CIII). Pregnant Women 8. If long-term suppression of Bartonella infection is required, erythromycin should be used. Tetracyclines should not be used during pregnancy. Candidiasis Prevention of Exposure 1. Candida organisms are common on mucosal surfaces and skin. No measures are available to reduce exposure to these fungi. Prevention of Disease 2. Data from prospective controlled trials indicate that fluconazole can reduce the risk for mucosal (oropharyngeal, esophageal, and vaginal) candidiasis and cryptococcosis as well in patients with advanced HIV disease (56-58). However, routine primary prophylaxis is not recommended because of the effectiveness of therapy for acute disease, the low mortality associated with mucosal candidiasis, the potential for resistant Candida organisms to develop, the possibility of drug interactions, and the cost of prophylaxis (DIII). Prevention of Recurrence 3. Many experts do not recommend chronic prophylaxis of recurrent oropharyngeal or vulvovaginal candidiasis for the same reasons that they do not recommend primary prophylaxis. However, if recurrences are frequent or severe, providers may consider administering an oral azole (fluconazole [CI] [56] or itraconazole solution [CI]). Other factors that influence choices about such therapy include the impact of the recurrences on the patient's well-being and quality of life, the need for prophylaxis for other fungal infections, cost, toxicities, drug interactions, and the potential to induce drug resistance among Candida and other fungi. Prolonged use of systemically absorbed azoles, particularly in patients with low CD4+ T-lymphocyte counts (i.e., less than 100 cells/µL), increases the risk for the development of azole resistance. 4. Adults or adolescents who have a history of documented esophageal candidiasis, particularly multiple episodes, should be considered candidates for chronic suppressive therapy. Fluconazole at a dose of 100-200 mg daily is appropriate (BI). However, the potential development of azole resistance should be taken into account when long-term azoles are considered. Special Considerations Children 5. Primary prophylaxis of candidiasis in HIV-infected infants is not indicated (DIII). 6. Suppressive therapy with systemic azoles should be considered for infants who have severe recurrent mucocutaneous candidiasis (CIII) and particularly for those who have esophageal candidiasis (BIII). Pregnant Women 7. Experience is limited with the use of systemic antifungal drugs during human pregnancy. Four cases of infants born with craniofacial and skeletal abnormalities following prolonged in utero exposure to fluconazole have been reported (59,50). In addition, itraconazole is embryotoxic and teratogenic in animal systems (61). These same potential risks of teratogenicity are presumed to apply to other systemically absorbed azole antifungals, such as ketoconazole. Therefore, chemoprophylaxis against oropharyngeal, esophageal, or vaginal candidiasis using systemically absorbed azoles should not be initiated during pregnancy (DIII), and azoles should be discontinued for HIV-infected women who become pregnant (DIII). Effective birth control measures should be recommended to all HIV-infected women on azole therapy for candidiasis (AIII). Cryptococcosis Prevention of Exposure 1. HIV-infected persons cannot completely avoid exposure to Cryptococcus neoformans. No evidence exists that exposure to pigeon droppings is associated with an increased risk for acquiring cryptococcosis. Prevention of Disease 2. Routine testing of asymptomatic persons for serum cryptococcal antigen is not recommended because of the low probability that the results will affect clinical decisions (DIII). 3. Prospective controlled trials indicate that fluconazole and itraconazole can reduce the frequency of cryptococcal disease among patients who have advanced HIV disease. However, most experts recommend that antifungal prophylaxis not be used routinely to prevent cryptococcosis because of the relative infrequency of cryptococcal disease, the lack of survival benefits associated with prophylaxis, the possibility of drug interactions, the potential development of antifungal drug resistance, and cost. The need for prophylaxis or suppressive therapy for other fungal infections (e.g., candidiasis, histoplasmosis, or coccidioidomycosis) should be considered in making decisions about prophylaxis for cryptococcosis. If used, fluconazole at doses of 100-200 mg daily is reasonable for patients whose CD4+ T-lymphocyte counts are less than 50 cells/µL (CI) (56-58). Prevention of Recurrence 4. Patients who complete initial therapy for cryptococcosis should be administered lifelong suppressive treatment (i.e., secondary prophylaxis or chronic maintenance therapy). Fluconazole is superior to itraconazole in preventing relapse of cryptococcal disease and is the preferred drug (AI). Discontinuation of Secondary Prophylaxis (Chronic Maintenance Therapy) 5. Although patients receiving secondary prophylaxis (chronic maintenance therapy) might be at low risk for recurrence of systemic mycosis when their CD4+ T-lymphocyte counts increase to greater than 100 cells/µL on HAART, the numbers of patients who have been evaluated are insufficient to warrant a recommendation to discontinue prophylaxis. Special Considerations Children 6. No data exist on which to base specific recommendations for children, but lifelong suppressive therapy with fluconazole after an episode of cryptococcosis is appropriate (AII). Pregnant Women 7. Prophylaxis with fluconazole or itraconazole should not be initiated during pregnancy because of the low incidence of cryptococcal disease, the lack of a recommendation for primary prophylaxis against cryptococcosis in nonpregnant adults, and potential teratogenic effects of these drugs during pregnancy (DIII) (59-61). For patients who conceive while being administered primary prophylaxis and who elect to continue their pregnancy, prophylaxis should be discontinued. The occurrence of craniofacial and skeletal abnormalities in infants following prolonged in utero exposure to fluconazole should be considered when assessing the therapeutic options for HIV-infected women who become pregnant and are receiving secondary prophylaxis (chronic maintenance therapy) for cryptococcosis (59,60). For such patients, therapy with amphotericin B may be preferred, especially during the first trimester. Effective birth control measures should be recommended to all HIV-infected women on azole therapy for cryptococcosis (AIII). Histoplasmosis Prevention of Exposure 1. Although HIV-infected persons living in or visiting histoplasmosis-endemic areas cannot completely avoid exposure to Histoplasma capsulatum, those whose CD4+ T-lymphocyte counts are less than 200 cells/µL should avoid activities known to be associated with increased risk (e.g., creating dust when working with surface soil; cleaning chicken coops that are heavily contaminated with droppings; disturbing soil beneath bird-roosting sites; cleaning, remodeling, or demolishing old buildings; and exploring caves) (CIII). Prevention of Disease 2. Routine skin testing with histoplasmin and serologic testing for antibody or antigen in histoplasmosis-endemic areas are not predictive of disease and should not be performed (DII). 3. Data from a prospective randomized controlled trial indicate that itraconazole can reduce the frequency of histoplasmosis among patients who have advanced HIV infection and who live in H. capsulatum-endemic areas (62). However, no survival benefit was observed among persons receiving itraconazole. Prophylaxis with itraconazole may be considered in patients with CD4+ T-lymphocyte counts less than 100 cells/µL who are at especially high risk because of occupational exposure or who live in a community with a hyperendemic rate of histoplasmosis (greater than or equal to 10 cases per 100 patient-years) (CI). Prevention of Recurrence 4. Patients who complete initial therapy for histoplasmosis should be administered lifelong suppressive treatment (i.e., secondary prophylaxis or chronic maintenance therapy) with itraconazole (200 mg twice a day) (AI) (63). Discontinuation of Secondary Prophylaxis (Chronic Maintenance Therapy) 5. Although patients receiving secondary prophylaxis (chronic maintenance therapy) might be at low risk for recurrence of systemic mycosis when their CD4+ T-lymphocyte counts increase to greater than 100 cells/µL on HAART, the numbers of patients who have been evaluated are insufficient to warrant a recommendation to discontinue prophylaxis. Special Considerations Children 6. Because primary histoplasmosis can lead to disseminated infection in children, a reasonable option is to administer lifelong suppressive therapy after an acute episode of the disease (AIII). Pregnant Women 7. Because of the embryotoxicity and teratogenicity of itraconazole in animal systems, primary prophylaxis against histoplasmosis should not be offered during pregnancy (DIII). These data as well as the observation of craniofacial and skeletal abnormalities in infants following prolonged in utero exposure to fluconazole should be considered when assessing the need for chronic maintenance therapy in HIV-infected pregnant women with histoplasmosis. For such patients, therapy with amphotericin B may be preferred, especially during the first trimester. Effective birth control measures should be recommended to all HIV-infected women on azole therapy for histoplasmosis (AIII). Coccidioidomycosis Prevention of Exposure 1. Although HIV-infected persons living in or visiting areas in which coccidioidomycosis is endemic cannot completely avoid exposure to Coccidioides immitis, they should, when possible, avoid activities associated with increased risk (e.g., those involving extensive exposure to disturbed native soil, for example, at building excavation sites or during dust storms) (CIII). Prevention of Disease 2. Routine skin testing with coccidioidin (spherulin) in coccidioidomycosis-endemic areas is not predictive of disease and should not be performed (DII). Within the endemic area, a positive serologic test might indicate an increased risk for active infection; however, routine testing does not appear to be useful and should not be performed (DIII). 3. Primary prophylaxis for HIV-infected persons who live in coccidioidomycosis-endemic areas is not routinely recommended. Prevention of Recurrence 4. Patients who complete initial therapy for coccidioidomycosis should be administered lifelong suppressive therapy (i.e., secondary prophylaxis or chronic maintenance therapy) (AII) using either 400 mg of fluconazole by mouth each day or 200 mg of itraconazole twice a day (64). Patients with meningeal disease require consultation with an expert. Discontinuation of Secondary Prophylaxis (Chronic Maintenance Therapy) 5. Although patients receiving secondary prophylaxis (chronic maintenance therapy) might be at low risk for recurrence of systemic mycosis when their CD4+ T-lymphocyte counts increase to greater than 100 cells/µL on HAART, the numbers of patients who have been evaluated are insufficient to warrant a recommendation to discontinue prophylaxis. Special Considerations Children 6. Although no specific data are available regarding coccidioidomycosis in HIV-infected children, a reasonable option is to administer lifelong suppressive therapy after an acute episode of the disease (AIII). Pregnant Women 7. The potential teratogenicity of fluconazole and itraconazole should be considered when assessing the therapeutic options for HIV-infected women who become pregnant while receiving chronic maintenance therapy for coccidiodomycosis. For such patients, therapy with amphotericin B may be preferred, especially during the first trimester. Effective birth control measures should be recommended for all HIV-infected women on azole therapy for coccidioidomycosis (AIII). Cytomegalovirus Disease Prevention of Exposure 1. HIV-infected persons who belong to risk groups with relatively low rates of seropositivity for cytomegalovirus (CMV) and who therefore cannot be presumed to be seropositive should be tested for antibody to CMV (BIII). These groups include patients who have not had male homosexual contact or used injection drugs. 2. HIV-infected adolescents and adults should be advised that CMV is shed in semen, cervical secretions, and saliva and that latex condoms must always be used during sexual contact to reduce the risk for exposure to CMV and to other sexually transmitted pathogens (AII). 3. HIV-infected adults and adolescents who are child-care providers or parents of children in child-care facilities should be informed that they are at increased risk for acquiring CMV infection (BI). Similarly, parents and other caretakers of HIV-infected children should be advised of the increased risk to children at these centers (BIII). The risk for acquiring CMV infection can be diminished by good hygienic practices such as hand washing (AII). 4. HIV-exposed infants and HIV-infected children, adolescents, and adults who are seronegative for CMV and require blood transfusion should be administered only CMV antibody-negative or leukocyte-reduced cellular blood products in nonemergency situations (BIII). Prevention of Disease 5. Prophylaxis with oral ganciclovir may be considered for HIV-infected adults and adolescents who are CMV seropositive and who have a CD4+ T-lymphocyte count of less than 50 cells/µL (CI) (65,66). Ganciclovir-induced neutropenia, anemia, conflicting reports of efficacy, lack of proven survival benefit, the risk for developing ganciclovir-resistant CMV, and cost are among the issues that should be considered when deciding whether to institute prophylaxis in individual patients. Acyclovir is not effective in preventing CMV disease, and valacyclovir is not recommended because of an unexplained trend toward increased deaths among persons with AIDS who were administered valacyclovir for CMV prophylaxis (67). Therefore, neither acyclovir nor valacyclovir should be used for this purpose (EI). The most important method for preventing severe CMV disease is recognition of the early manifestations of the disease. Early recognition of CMV retinitis is most likely when the patient has been educated on this topic. Patients should be made aware of the significance of increased floaters in the eye and should be advised to assess their visual acuity regularly by using simple techniques such as reading newsprint (BIII). Regular funduscopic examinations performed by an ophthalmologist are recommended by some experts for patients with low (e.g., less than 50 cells/µL) CD4+ T-lymphocyte counts (CIII). Prevention of Recurrence 6. CMV disease is not cured with courses of the currently available antiviral agents (e.g., ganciclovir, foscarnet, or cidofovir). Following induction therapy, secondary prophylaxis (chronic maintenance therapy) is recommended for life (AI). Regimens that are effective for chronic suppression include parenteral or oral ganciclovir, parenteral foscarnet, combined parenteral ganciclovir and foscarnet, parenteral cidofovir, and (for retinitis only) ganciclovir administration via intraocular implant plus oral ganciclovir (AI) (68-72). The intraocular implant alone does not provide protection to the contralateral eye or to other organ systems. The choice of a chronic maintenance regimen for patients treated for CMV disease should be made in consultation with an expert. For patients with retinitis, this decision should be made in consultation with an ophthalmologist and should take into consideration the anatomic location of the retinal lesion, vision in the contralateral eye, the immunologic and virologic status of the patient, and the patient's response to HAART (BIII). Discontinuation of Secondary Prophylaxis (Chronic Maintenance Therapy) 7. Several studies have found that maintenance therapy can be discontinued in patients with CMV retinitis whose CD4+ T-lymphocyte counts have increased to greater than 100-150 cells/µL and whose HIV plasma RNA levels have been suppressed in response to HAART (73-75). These patients largely have remained disease-free for greater than 30-90 weeks, whereas in the pre-HAART era, retinitis typically recurred in 6-8 weeks. Discontinuation of prophylaxis may be considered in patients with a sustained (e.g., greater than 3-6 month) increase in CD4+ T-lymphocyte count to greater than 100-150 cells/µL on HAART (CIII). Such decisions should be made in consultation with an ophthalmologist and should take into account such factors as magnitude and duration of CD4+ T-lymphocyte increase, magnitude and duration of viral load suppression, anatomic location of the retinal lesion, vision in the contralateral eye, and the feasibility of regular ophthalmic monitoring (CII) (73-75). Restarting Secondary Prophylaxis 8. No data exist to guide recommendations for reinstituting secondary prophylaxis. Pending the availability of such data, a reasonable approach would be to restart prophylaxis when the CD4+ T-lymphocyte count has decreased to less than 50-100 cells/µL (CIII). Special Considerations Children 9. Some experts recommend obtaining a CMV urine culture on all HIV-infected (or exposed) infants at birth or at an early postnatal visit to identify those infants with congenital CMV infection (CIII). In addition, beginning at 1 year of age, CMV antibody testing on an annual basis may be considered for CMV-seronegative (and culture-negative) HIV-infected infants and children who are severely immunosuppressed (Table 9) (CIII). Annual testing will allow identification of children who have acquired CMV infection and might benefit from screening for retinitis. 10. HIV-infected children who are CMV-infected and severely immunosuppressed might benefit from a dilated retinal examination performed by an ophthalmologist every 4-6 months (CIII). In addition, older children should be counseled to be aware of floaters in the eye, similar to the recommendation for adults (BIII). 11. Oral ganciclovir results in reduced CMV shedding in CMV-infected children and may be considered for primary prophylaxis against CMV disease in CMV-infected children who are severely immunosuppressed (e.g., CD4+ T-lymphocyte count less than 50 cells/µL) (CII). 12. For children with CMV disease, no data are available to guide decisions concerning discontinuation of secondary prophylaxis (chronic maintenance therapy) when the CD4+ T-lymphocyte count has increased in response to HAART. Pregnant Women 13. Because of the lack of a recommendation for routine use of ganciclovir among nonpregnant adults and the lack of experience with this drug during pregnancy, ganciclovir is not recommended for primary prophylaxis against CMV disease during pregnancy (DIII). Ganciclovir should be discontinued for patients who conceive while being administered primary prophylaxis. Because of the risks to maternal health, prophylaxis against recurrent CMV disease is indicated during pregnancy (AIII). The choice of agents to be used in pregnancy should be individualized after consultation with experts. Herpes Simplex Virus Disease Prevention of Exposure 1. HIV-infected persons should use latex condoms during every act of sexual intercourse to reduce the risk for exposure to herpes simplex virus (HSV) and to other sexually transmitted pathogens (AII). They should specifically avoid sexual contact when herpetic lesions (genital or orolabial) are evident (AII). Prevention of Disease 2. Prophylaxis of initial episodes of HSV disease is not recommended (DIII). Prevention of Recurrence 3. Because acute episodes of HSV infection can be treated successfully, chronic therapy with acyclovir is not required after lesions resolve. However, persons who have frequent or severe recurrences can be administered daily suppressive therapy with oral acyclovir or famciclovir (AI) (76,77). Valacyclovir also is an option (CIII). Intravenous foscarnet or cidofovir can be used to treat infection due to acyclovir-resistant isolates of HSV, which are routinely resistant to ganciclovir as well (AII). Special Considerations Children 4. The recommendations for preventing initial disease and recurrence among adults and adolescents apply to children as well. Pregnant Women 5. Oral acyclovir prophylaxis during late pregnancy is a controversial strategy recommended by some experts to prevent neonatal herpes transmission. However, such prophylaxis is not routinely recommended. For patients who have frequent, severe recurrences of genital HSV disease, acyclovir prophylaxis might be indicated (BIII). No pattern of adverse pregnancy outcomes has been reported after acyclovir exposures (78). Varicella-Zoster Virus Infection Prevention of Exposure 1. HIV-infected children and adults who are susceptible to varicella-zoster virus (VZV) (i.e., those who have no history of chickenpox or shingles or are seronegative for VZV) should avoid exposure to persons with chickenpox or shingles (AII). Household contacts (especially children) of susceptible HIV-infected persons should be vaccinated against VZV if they have no history of chickenpox and are seronegative for HIV, so that they will not transmit VZV to their susceptible HIV-infected contacts (BIII). Prevention of Disease 2. Very little data regarding the safety and efficacy of varicella vaccine in HIV-infected adults are available, and no recommendation for its use can be made for this population. (See Special Considerations/Children, below, for information about the use of varicella vaccine in children.) 3. For the prophylaxis of chickenpox, HIV-infected children and adults who are susceptible to VZV (i.e., those who have no history of chickenpox or shingles or who have no detectable antibody against VZV) should be administered varicella zoster immune globulin (VZIG) as soon as possible but within 96 hours after close contact with a patient who has chickenpox or shingles (AIII). Data are lacking on the effectiveness of acyclovir for preventing chickenpox in susceptible HIV-infected children or adults. 4. No preventive measures are currently available for shingles. Prevention of Recurrence 5. No drug has been proven to prevent the recurrence of shingles in HIV-infected persons. Special Considerations Children 6. HIV-infected children who are asymptomatic and not immunosuppressed (i.e., in immunologic category 1, Table 9) should receive live attenuated varicella vaccine at 12-15 months of age or later (BII). Varicella vaccine should not be administered to other HIV-infected children because of the potential for disseminated viral infection (EIII). Pregnant Women 7. VZIG is recommended for VZV-susceptible, HIV-infected pregnant women within 96 hours after exposure to VZV (AIII). If oral acyclovir is used, VZV serology should be performed so that the drug can be discontinued if the patient is seropositive for VZV (BIII). Human Herpesvirus 8 Infection Prevention of Exposure 1. The mechanism of transmitting human herpesvirus 8 (HHV-8), the herpesvirus associated with Kaposi's sarcoma (KS), is not known. Epidemiologic evidence suggests that sexual transmission is likely among men who have sex with men and can occur among heterosexuals as well. However, the virus has been detected more frequently in saliva than in semen from HHV-8-seropositive HIV-infected persons. Although the efficacy of condom use for preventing HHV-8 infection has not been established, HIV-infected persons should use latex condoms during every act of sexual intercourse to reduce the risk for exposure to sexually transmitted pathogens (AII). Prevention of Disease 2. Because clinical use of routine serologic testing to identify HHV-8 infection has not been established, no recommendation for serologic testing can be made at this time. 3. Lower rates of KS have been observed among AIDS patients treated with ganciclovir or foscarnet for CMV retinitis (68). HHV-8 replication in vitro is inhibited by ganciclovir, foscarnet, and cidofovir. However, because the efficacy and clinical use of these drugs in preventing KS have not been established, no recommendation can be made concerning the use of these or other drugs to prevent KS in individuals coinfected with HIV and HHV-8. 4. Potent antiretroviral drug combinations that suppress HIV replication reduce the frequency of KS in HIV-infected persons and should be considered for all persons who qualify for such therapy (BII). Prevention of Recurrence 5. Effective suppression of HIV replication with antiretroviral drugs in HIV-infected patients with KS might prevent KS progression or the development of new lesions and should be considered for all persons with KS (BII). Special Considerations Children 6. In parts of the world where HHV-8 is endemic, horizontal transmission might occur among young children, possibly via saliva. However, no recommendations are currently available for preventing HHV-8 transmission from child to child. Human Papillomavirus Infection Prevention of Exposure 1. HIV-infected persons should use latex condoms during every act of sexual intercourse to reduce the risk for exposure to sexually transmitted pathogens (AII), although little evidence exists to suggest that condoms reduce the risk for infection with human papillomavirus (HPV). Prevention of Disease HPV-associated Genital Epithelial Cancers in HIV-infected Women 2. After a complete history of previous cervical disease has been obtained, HIV-infected women should have a pelvic examination and a Pap smear. In accordance with the recommendation of the Agency for Health Care Policy and Research, the Pap smear should be obtained twice in the first year after diagnosis of HIV infection and, if the results are normal, annually thereafter (AII). 3. If the results of the Pap smear are abnormal, care should be provided according to the Interim Guidelines for Management of Abnormal Cervical Cytology published by a National Cancer Institute Consensus Panel and briefly summarized in Recommendations 4-8, which follow (79). 4. For patients whose Pap smears are interpreted as atypical squamous cells of undetermined significance (ASCUS), several management options are available; the choice depends in part on whether the interpretation of ASCUS is qualified by a statement indicating that a neoplastic process is suspected. Follow-up by Pap tests without colposcopy is acceptable, particularly when the diagnosis of ASCUS is not qualified further or the cytopathologist suspects a reactive process. In such situations, Pap tests should be repeated every 4-6 months for 2 years until three consecutive smears have been negative. If a second report of ASCUS occurs in the 2-year follow-up period, the patient should be considered for colposcopic evaluation (BIII). 5. Women who have a diagnosis of unqualified ASCUS associated with severe inflammation should be evaluated for an infectious process. If specific infections are identified, reevaluation should be performed after appropriate treatment, preferably after 2-3 months (BIII). 6. If the diagnosis of ASCUS is qualified by a statement indicating that a neoplastic process is suspected, the patient should be managed as if a low-grade squamous intraepithelial lesion (LSIL) were present (see Recommendation 7, which follows) (BIII). If a patient who has a diagnosis of ASCUS is at high risk (i.e., previous positive Pap tests or poor adherence to follow-up), the option of colposcopy should be considered (BIII). 7. Several management options are available for patients who have LSIL. Follow up with Pap tests every 4-6 months is used by many clinicians and is currently used in countries outside the United States as an established method of management. Patients managed in this way must be carefully selected and considered reliable for follow-up. If repeat smears show persistent abnormalities, colposcopy and directed biopsy are indicated (BIII). Colposcopy and directed biopsy of any abnormal area on the ectocervix constitute another appropriate option (BIII). 8. Women who have cytologic diagnosis of high-grade squamous intraepithelial lesions (HSILs) or squamous cell carcinoma should undergo colposcopy and directed biopsy (AII). 9. No data are available to suggest that these guidelines to prevent cervical disease should be modified for women on HAART. HPV-associated Anal Intraepithelial Neoplasia and Anal Cancer in HIV-infected, Men Who Have Sex With Men 10. Evidence from several studies shows that HPV-positive men who have sex with men are at increased risk for anal HSILs and might be at increased risk for anal cancer. In view of this evidence, coupled with a recent cost-effectiveness analysis projecting that screening and treatment for anal HSILs provide clinical benefits comparable to other measures to prevent OIs in HIV-infected persons (80), anal cytology screening of HIV-infected men who have sex with men might become a useful preventive measure in the near future. However, further studies of screening and treatment programs for anal HSILs need to be carried out before recommendations for routine anal cytology screening can be made. Prevention of Recurrence 11. The risks for recurrence of squamous intraepithelial lesions and cervical cancer after conventional therapy are increased among HIV-infected women. The prevention of illness associated with recurrence depends on careful follow-up of patients after treatment. Patients should be monitored with frequent cytologic screening and, when indicated, with colposcopic examination for recurrent lesions (AI) (79). 12. In one recent study of HIV-infected women treated for HSILs using standard therapy, low-dose intravaginal 5-fluorouracil (2 grams twice a week for 6 months) reduced the short-term risk for recurrence and possibly the grade of recurrence (81). However, clinical experience with this therapy is too limited to provide a recommendation for routine use. Special Considerations Pregnant Women 13. Use of intravaginal 5-fluorouracil to prevent recurrent dysplasia is not recommended during pregnancy. Hepatitis C Virus Infection Prevention of Exposure 1. The chief route of hepatitis C virus (HCV) transmission in the United States is injection drug use. Because injection drug use is a complex behavior, clinicians should assess the individual's readiness to change this practice and encourage efforts to provide patient education and support directed at recovery. Patients who inject drugs should be advised (82-84) --
If they are continuing to inject drugs, patients should be advised (BIII) --
If they are continuing to use illegal drugs intranasally ("snorting"), patients should be advised (BIII) --
2. Persons considering tattooing or body piercing should be informed of potential risks of acquiring bloodborne infections, which could be transmitted if equipment is not sterile or if proper infection control procedures are not followed (e.g., washing hands, using latex gloves, and cleaning and disinfecting surfaces) (84) (BIII). 3. To reduce risks for acquiring bloodborne infections, patients should be advised not to share dental appliances, razors, or other personal care articles (BIII). 4. Although the efficiency of sexual transmission of HCV remains controversial, safe-sexual practices should be encouraged, and barrier precautions (e.g., latex condoms) are recommended to reduce the risk for exposure to sexually transmitted pathogens (AII). Prevention of Disease 5. HIV-infected patients should be screened for HCV infection by using enzyme immunoassays (EIAs) licensed for detection of antibody to HCV (anti-HCV) in blood (BIII). Positive anti-HCV results should be verified with additional testing (i.e., recombinant immunoblot assay [RIBA™] or reverse transcriptase polymerase chain reaction for HCV RNA). The presence of HCV RNA in blood might also be assessed in HIV-infected persons with undetectable antibody but other evidence of chronic liver disease (e.g., unexplained elevated liver-specific enzymes) or when acute HCV infection is suspected (CIII). 6. Persons coinfected with HIV and HCV should be advised not to drink excessive amounts of alcohol (AII). Avoiding alcohol altogether might be prudent because it is unclear whether even occasional moderate alcohol use (e.g., less than 12 ounces of beer or less than 10 grams of alcohol per week) increases the incidence of cirrhosis among HCV-infected persons (CIII). 7. Patients with chronic hepatitis C should be vaccinated against hepatitis A because a) the risk for fulminant hepatitis associated with hepatitis A appears increased in HCV-coinfected persons; b) hepatitis A vaccine is safe for HIV-infected persons; and c) although immunogenicity is reduced in patients with advanced HIV infection, more than two thirds of patients develop protective antibody responses (BIII). Prevaccination screening for antibody to hepatitis A virus is cost-effective and therefore recommended when greater than 30% prevalence of hepatitis A virus antibody is expected in the population being screened (e.g., persons greater than 40 years of age) (85) (BIII). 8. HIV-HCV-coinfected patients have a higher incidence of chronic liver disease than patients infected with HIV alone (86) and should be evaluated for chronic liver disease and for the possible need for treatment (83). However, limited data exist regarding the safety and efficacy of antiviral treatment of patients coinfected with HIV and HCV. Moreover, because the optimal means of treating coinfected patients has not been established and many HIV-infected patients have conditions that complicate therapy (e.g., depression or illicit drug use), this care should occur in a clinical trial or be coordinated by providers with experience treating both HIV and HCV infections (BIII). 9. In some studies, the incidence of antiretroviral-associated liver enzyme elevations has been increased in patients coinfected with HIV and HCV (87); such increases might not require treatment modifications. Thus, although liver enzymes should be carefully monitored, HAART should not be routinely withheld from patients coinfected with HIV and HCV (DIII). However, coinfected patients initiating antiretroviral therapy might have an inflammatory reaction that mimics an exacerbation of underlying liver disease. In this situation, careful monitoring of liver function is required. Prevention of Recurrence 10. If the serum HCV RNA level becomes undetectable during HCV therapy and remains undetectable for 6 months after HCV therapy is stopped (sustained virologic response), greater than 90% of HIV-uninfected patients with hepatitis C will remain HCV RNA negative for greater than 5 years and have improved liver histology (88). For HIV-HCV-coinfected patients, the durability of treatment response and requirement for maintenance therapy are unknown. Special Considerations Children 11. Children born to women coinfected with HIV and HCV should be tested for HCV infection (82) (BI). In children with perinatal HCV infection, maternal HCV antibody can persist for up to 18 months, and HCV RNA can be intermittently undetectable. Thus, testing should be performed at or after 2 years of age. If earlier diagnosis is needed, HCV RNA should be assessed in more than one infant blood specimen obtained after 1 month of age. The average rate of HCV infection among infants born to coinfected women is approximately 15% (range, 5-36%) (89). Data are limited on the natural history and treatment of HCV infection in children. References
* Only filters capable of removing particles 1 µm in diameter should be considered. Filters that provide the greatest assurance of oocyst removal include those that operate by reverse osmosis, those labeled as absolute 1-µm filters, and those labeled as meeting NSF (National Sanitation Foundation) standard no. 53 for cyst removal. The nominal 1-µm filter rating is not standardized, and many filters in this category might not be capable of removing 99% of oocysts. ** Sources of bottled water (e.g., wells, springs, municipal tap-water supplies, rivers, and lakes) and methods for its disinfection differ; therefore, all brands should not be presumed to be free of cryptosporidial oocysts. Water from wells and springs is much less likely to be contaminated by oocysts than water from rivers or lakes. Treatment of bottled water by distillation or reverse osmosis ensures oocyst removal. Water passed through an absolute 1-µm filter or a filter labeled as meeting NSF standard no. 53 for cyst removal before bottling will provide nearly the same level of protection. Use of nominal 1-µm filters by bottlers as the only barrier to Cryptosporidia might not result in the removal of 99% of oocysts. Box System used to rate the strength of recommendations and quality of supporting evidence*
* Modified from Gross PA, Barrett TL, Dellinger EP, et al., 1994 (12). Return to top. Table 1 To print large tables and graphs users may have to change their printer settings to landscape and use a small font size.
TABLE 1. Prophylaxis to prevent first episode of opportunistic disease in adults and
adolescents infected with human immunodeficiency virus
=====================================================================================================================
Preventive Regimens
----------------------------------------------------------------------------
Pathogen Indication First Choice Alternatives
-----------------------------------------------------------------------------------------------------
I. Strongly
recommended as
standard of care
Pneumocystis carinii* CD4+ count <200/µL Trimethoprim- Dapsone, 50 mg po
or oropharyngeal sulfamethoxazole b.i.d. or 100 mg po
candidiasis (TMP-SMZ), 1 DS po q.d. (BI); dapsone,
q.d. (AI) 50 mg po q.d. plus
pyrimethamine,
TMP-SMZ, 1 SS po 50 mg po q.w. plus
q.d. (AI) leucovorin, 25 mg po
q.w. (BI); dapsone,
200 mg po plus
pyrimethamine,
75 mg po plus
leucovorin, 25 mg po
q.w. (BI); aerosolized
pentamidine, 300 mg
q.m. via
Respirgard II(TM)
nebulizer (BI);
atovaquone, 1500 mg
po q.d. (BI);
TMP-SMZ, 1 DS po
t.i.w. (BI)
Mycobacterium TST reaction >=5mm or Isoniazid, 300 mg po Rifabutin 300 mg po
tuberculosis prior positive TST plus pyridoxine, q.d. plus
Isoniazid-sensitive+ result without 50 mg po q.d. x 9 mo pyrazinamide,
treatment or contact (AII) or isoniazid, 20 mg/kg po q.d. x 2
with case of active 900 mg po plus mo (BIII); rifampin
tuberculosis pyridoxine, 100 mg 600 mg po q.d. x 4
po b.i.w. x 9 mo (BI); mo (BIII)
rifampin, 600 mg plus
pyrazinamide,
20 mg/kg po q.d. x 2
mo (AI)
Isoniazid-resistant Same; high Rifampin 600 mg plus Rifabutin, 300 mg
probability of pyrazinamide, plus pyrazinamide
exposure to 20 mg/kg po q.d. x 2 20 mg/kg po q.d. x 2
isoniazid-resistant mo (AI) mo (BIII); rifampin,
tuberculosis 600 mg po q.d. x 4
mo (BIII); Rifabutin,
300 mg po q.d. x 4
mo (CIII)
Multidrug-(isoniazid Same; high Choice of drugs None
and rifampin) probability of requires consultation
resistant exposure to with public health
multidrug-resistant authorities
tuberculosis
Toxoplasma gondii& IgG antibody to TMP-SMZ, 1 DS po TMP-SMZ, 1 SS po
Toxoplasma and q.d. (AII) q.d. (BIII): dapsone,
CD4+ count <100/µL 50 mg po q.d. plus
pyrimethamine,
50 mg po q.w. plus
leukovorin, 25 mg po
q.w. (BI); atovaquone,
1500 mg po q.d. with
or without
pyrimethamine,
25 mg po q.d. plus
leukovorin, 10 mg po
q.d. (CIII)
Mycobacterium CD4+ count <50/µL Azithromycin, Rifabutin, 300 mg po
avium complex@ 1,200 mg po q.w., (AI) q.d. (BI);
or clarithromycin, azithromycin,
500 mg po b.i.d. (AI) 1,200 mg po q.w. plus
rifabutin, 300 mg po
q.d. (CI)
Varicella zoster virus Significant exposure Varicella zoster
(VZV) to chickenpox or immune globulin
shingles for patients (VZIG), 5 vials
who have no history (1.25 mL each) im,
of either condition or, administered <=96 h
if available, negative after exposure, ideally
antibody to VZV within 48 h (AIII)
II. Generally
recommended
Streptococcus All patients Pneumococcal None
pneumoniae** vaccine, 0.5 mL im
(CD4+ >=200/µL [BIl];
CD4+ <200/µL [CIII])-
might reimmunize if
initial immunization
was given when CD4+
<200/µL and if CD4+
increases to >200/µL
on HAART(CIII)
Hepatitis B virus++ All susceptible Hepatitis B vaccine: None
(anti-HBc-negative) 3 doses (BII)
patients
Influenza virus++ All patients (annually, Whole or split virus, Rimantadine, 100 mg
before influenza 0.5 mL im/yr (BIII) po b.i.d. (CIII), or
season) amantadine, 100 mg
po b.i.d. (CIII)
Hepatitis A virus++ All susceptible Hepatitis A vaccine: None
(anti-HAV-negative) two doses (BIII)
patients with chronic
hepatitis C
III. Not routinely
indicated
Bacteria Neutropenia Granulocyte- None
colony-stimulating
factor (G-CSF),
5-10 µg/kg sc q.d. x
2-4 w or granulocyte-
macrophage
colony-stimulating
factor (GM-CSF),
250 µg/m² iv over 2 h
q.d. x 2-4 w (CII)
Cryptococcus CD4+ count <50/µL Fluconazole, Itraconazole, 200 mg
neoformans&& 100-200 mg po q.d. po q.d. (CIII)
(CI)
Histoplasma CD4+ count <100/µL, Itraconazole capsule, None
capsulatum&& endemic geographic 200 mg po q.d.(CI)
area
Cytomegalovirus CD4+ count <50/µL Oral ganciclovir, 1 g None
(CMV)@@ and CMV antibody po t.i.d. (CI)
positivity
-----------------------------------------------------------------------------------------------------
NOTES: Information included in these guidelines might not represent Food and Drug Administration (FDA)
approval or approved labeling for the particular products or indications in question. Specifically, the terms
"safe" and "effective" might not be synonymous with the FDA-defined legal standards for product approval.
The Respirgard II(TM) nebulizer is manufactured by Marquest, Englewood, Colorado. Letters and Roman numerals
in parentheses after regimens indicate the strength of the recommendation and the quality of evidence
supporting it (see Box, page 3).
ABBREVIATIONS: Anti-HBc = antibody to hepatitis B core antigen; b.i.w.= twice a week; DS = double-strength
tablet; HAART = highly active antiretroviral therapy; HAV = hepatitis A virus; HIV = human immunodeficiency
virus; im = intramuscular; iv = intravenous; po = by mouth; q.d. = daily; q.m. = monthly; q.w. = weekly;
SS= single-strength tablet; t.i.w. = three times a week; TMP-SMZ = trimethoprim-sulfamethoxazole;
sc = subcutaneous; and TST = tuberculin skin test.
* Prophylaxis should also be considered for persons with a CD4+ percentage of <14%, for persons with a
history of an AIDS-defining illness, and possibly for those with CD4+ counts 200 but <250 cells/µL.
TMP-SMZ also reduces the frequency of toxoplasmosis and some bacterial infections. Patients receiving
dapsone should be tested for glucose-6 phosphate dehydrogenase deficiency. A dosage of 50 mg q.d.
is probably less effective than that of 100 mg q.d. The efficacy of parenteral pentamidine (e.g.,
4 mg/kg/month) is uncertain. Fansidar (sulfadoxine-pyrimethamine) is rarely used because of severe
hypersensitivity reactions. Patients who are being administered therapy for toxoplasmosis with
sulfadiazine-pyrimethamine are protected against Pneumocystis carinii pneumonia and do not need
additional prophylaxis against PCP.
+ Directly observed therapy is recommended for isoniazid, 900 mg b.i.w.; isoniazid regimens should include
pyridoxine to prevent peripheral neuropathy. Rifampin should not be administered concurrently with
protease inhibitors or nonnucleoside reverse transcriptase inhibitors. Rifabutin should not be given with
hard-gel saquinavir or delavirdine; caution is also advised when the drug is coadministered with soft-gel
saquinavir. Rifabutin may be administered at a reduced dose (150 mg q.d.) with indinavir, nelfinavir, or
amprenavir; at a reduced dose of 150 mg q.o.d. (or 150 mg three times weekly) with ritonavir; or at an
increased dose (450 mg q.d.) with efavirenz; information is lacking regarding coadministration of rifabutin
with nevirapine. Exposure to multidrug-resistant tuberculosis might require prophylaxis with two drugs;
consult public health authorities. Possible regimens include pyrazinamide plus either ethambutol or a
fluoroquinolone.
& Protection against toxoplasmosis is provided by TMP-SMZ, dapsone plus pyrimethamine, and possibly
by atovaquone. Atovaquone may be used with or without pyrimethamine. Pyrimethamine alone probably
provides little, if any, protection.
@ See footnote + regarding use of rifabutin with protease inhibitors or nonnucleoside reverse transcriptase
inhibitors.
** Vaccination should be offered to persons who have a CD4+ T-lymphocyte count <200 cells/µL, although
the efficacy might be diminished. Revaccination 5 years after the first dose or sooner if the initial
immunization was given when the CD4+ count was <200 cells/µL and the CD4+ count has increased to
>200 cells/µL on HAART is considered optional. Some authorities are concerned that immunizations might
stimulate the replication of HIV. However, one study showed no adverse effect of pneumococcal
vaccination on patient survival (McNaghten AD, Hanson DL, Jones JL, Dworkin MS, Ward JW, and the
Adult/Adolescent Spectrum of Disease Group. Effects of antiretroviral therapy and opportunistic illness
primary chemoprophylaxis on survival after AIDS diagnosis. AIDS 1999 [in press]).
++ These immunizations or chemoprophylactic regimens do not target pathogens traditionally classified as
opportunistic but should be considered for use in HIV-infected patients as indicated. Data are inadequate
concerning clinical benefit of these vaccines in this population, although it is logical to assume that those
patients who develop antibody responses will derive some protection. Some authorities are concerned
that immunizations might stimulate HIV replication, although for influenza vaccination, a large
observational study of HIV-infected persons in clinical care showed no adverse effect of this vaccine,
including multiple doses, on patient survival (J. Ward, CDC, personal communication). Hepatitis B vaccine
has been recommended for all children and adolescents and for all adults with risk factors for hepatitis
B virus (HBV). Rimantadine and amantadine are appropriate during outbreaks of influenza A. Because
of the theoretical concern that increases in HIV plasma RNA following vaccination during pregnancy
might increase the risk of perinatal transmission of HIV, providers may wish to defer vaccination until
after antiretroviral therapy is initiated. For additional information regarding vaccination against hepatitis
A and B and vaccination and antiviral therapy against influenza see CDC. Prevention of hepatitis A through
active or passive immunization: recommendations of the Advisory Committee on Immunization Practices
(ACIP). MMWR 1996;45(No. RR-15); CDC. Hepatitis B virus: a comprehensive strategy for eliminating
transmission in the United States through universal childhood vaccination: recommendations of the
Advisory Committee on Immunization Practices (ACIP). MMWR 1991;40(No. RR-13); and CDC. Prevention
and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP).
MMWR 1999;48(No. RR-4).
&& In a few unusual occupational or other circumstances, prophylaxis should be considered; consult a
specialist.
@@ Acyclovir is not protective against CMV. Valacyclovir is not recommended because of an unexplained
trend toward increased mortality observed in persons with AIDS who were being administered this drug
for prevention of CMV disease.
=====================================================================================================================
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TABLE 2. Prophylaxis to prevent recurrence of opportunistic disease (after
chemotherapy for acute disease) in adults and adolescents infected with human
immunodeficiency virus
=====================================================================================================================
Preventive Regimens
-------------------------------------------------------------------------------------
Pathogen Indication First Choice Alternatives
--------------------------------------------------------------------------------------------------------------
I. Recommended for life as standard of care
Pneumocystis carinii Prior P. carinii Trimethoprim- Dapsone, 50 mg po b.i.d.
pneumonia sulfamethoxazole or 100 mg po q.d. (BI);
(TMP-SMZ), 1 DS po q.d. dapsone, 50 mg po q.d.
(AI); plus pyrimethamine,
50 mg po q.w. plus
TMP-SMZ 1 SS po q.d. leucovorin, 25 mg po q.w.
(AI) (BI); dapsone, 200 mg po
plus pyrimethamine,
75 mg po plus leucovorin,
25 mg po q.w. (BI);
aerosolized pentamidine,
300 mg q.m. via
Respirgard II(TM) nebulizer
(BI); atovaquone,
1500 mg po q.d. (BI);
TMP-SMZ, 1 DS po t.i.w.
(CI)
Toxoplasma gondii* Prior toxoplasmic Sulfadiazine, 500-1,000 Clindamycin, 300-450 mg
encephalitis mg po q.i.d. plus po q 6-8 h plus
pyrimethamine, 25-75 pyrimethamine,
mg po q.d. plus 25-75 mg po q.d. plus
leucovorin, 10-25 mg po leucovorin, 10-25 mg po
q.d. (AI) q.d. (BI); atovaquone,
750 mg po q. 6-12 h with
or without
pyrimethamine, 25 mg po
q.d. plus leucovorin,
10 mg po q.d. (CIII)
Mycobacterium Documented Clarithromycin, 500 mg Azithromycin, 500 mg po
avium complex + disseminated po b.i.d. (AI) plus q.d. (AII) plus ethambutol,
disease ethambutol, 15 mg/kg po 15 mg/kg po q.d.(AII);
q.d.(AII); with or without with or without rifabutin,
rifabutin, 300 mg po q.d. 300 mg po q.d.(CI)
(CI)
Cytomegalovirus Prior end-organ Ganciclovir, 5-6 mg/kg iv Cidofovir, 5 mg/kg iv
disease 5-7 days/wk or 1,000 mg q.o.w. with probenecid
po t.i.d. (AI); or foscarnet, 2 grams po 3 hours
90-120 mg/kg iv q.d. (AI); before the dose followed
or (for retinitis) by 1 gram po given
ganciclovir 2 hours after the dose,
sustained-release implant and 1 gram po 8 hours
q 6-9 months plus after the dose (total of
ganciclovir, 1.0-1.5 g po 4 grams) (AI). Fomivirsen
t.i.d. (AI) 1 vial (330 µg) injected
into the vitreous, then
repeated every 2-4 wks
(AI)
Cryptococcus Documented Fluconazole, 200 mg po Amphotericin B,
neoformans disease q.d. (AI) 0.6-1.0 mg/kg iv
q.w.-t.i.w. (AI);
itraconazole, 200 mg po
q.d. (BI)
Histoplasma Documented Itraconazole capsule, Amphotericin B,
capsulatum disease 200 mg po b.i.d. (AI) 1.0 mg/kg iv q.w. (AI)
Coccidioides Documented Fluconazole, 400 mg po Amphotericin B,
immitis disease q.d. (AII) 1.0 mg/kg iv q.w. (AI);
itraconazole, 200 mg po
b.i.d. (AII)
Salmonella species, Bacteremia Ciprofloxacin, 500 mg po Antibiotic
(non-typhi)& b.i.d. for several months chemoprophylaxis with
(BII) another active agent (CIII)
II. Recommended only if subsequent episodes are frequent or severe
Herpes simplex virus Frequent/severe Acyclovir, 200 mg po t.i.d. Valacyclovir, 500 mg po
recurrences or 400 mg po b.i.d.(AI) b.i.d. (CIII)
Famciclovir 500 mg po
b.i.d. (AI)
Candida Frequent/severe Fluconazole 100-200 mg Itraconazole solution,
(oropharyngeal or recurrences po q.d. (CI) 200 mg po q.d. (CI);
vaginal) ketoconazole, 200 mg po
q.d. (CIII)
Candida (esophageal) Frequent/severe Fluconazole 100-200 mg Itraconazole solution,
recurrences po q.d. (BI) 200 mg po q.d. (BI);
ketoconazole, 200 mg po
q.d. (CIII)
--------------------------------------------------------------------------------------------------------------
NOTES: Information included in these guidelines might not represent Food and Drug Administration (FDA)
approval or approved labeling for the particular products or indications in question. Specifically, the terms
"safe" and "effective" might not be synonymous with the FDA-defined legal standards for product approval.
The Respirgard II(TM) nebulizer is manufactured by Marquest, Englewood, Colorado. Letters and Roman
numerals in parentheses after regimens indicate the strength of the recommendation and the quality of
evidence supporting it (see Box, page 3).
ABBREVIATIONS: b.i.d. = twice a day; DS = double-strength tablet; po = by mouth; q.d. = daily; q.m. = monthly;
q.w. = weekly; q.o.w. = every other week; SS = single-strength tablet; t.i.d. = three times a day; t.i.w. = three
times a week; and TMP-SMZ = trimethoprim-sulfamethoxazole.
* Pyrimethamine-sulfadiazine confers protection against PCP as well as toxoplasmosis; clindamycin-
pyrimethamine does not.
+ Many multiple-drug regimens are poorly tolerated. Drug interactions (e.g., those seen with clarithromycin
and rifabutin) can be problematic; rifabutin has been associated with uveitis, especially when administered
at daily doses of >300 mg or concurrently with fluconazole or clarithromycin. Rifabutin should not be
administered concurrently with hard-gel saquinavir or delavirdine; caution is also advised when the drug
is coadministered with soft-gel saquinavir. Rifabutin may be administered at reduced dose (150 mg q.d.
with indinavir, nelfinavir, or amprenavir; or 150 mg q.o.d. with ritonavir) or at increased dose (450 mg q.d.)
with efavirenz (CDC. Prevention and treatment of tuberculosis among patients infected with human immu-
nodeficiency virus: principles of therapy and revised recommendations. MMWR 1998;47[RR-20]). Information
is lacking regarding coadministration of rifabutin with nevirapine.
& Efficacy of eradication of Salmonella has been demonstrated only for ciprofloxacin.
=====================================================================================================================
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TABLE 3. Effects of food on drugs used to prevent opportunistic infections
===============================================================================================
Drug Food Effect Recommendation
---------------------------------------------------------------------------------------------
Atovaquone Bioavailability increased up to Administer with food.
threefold with high-fat meal.
Ganciclovir (capsules) High-fat meal results in 22% Administer with food.
increase in the area under the
curve (AUC).
Itraconazole (capsules) Significant increase in Administer with food; avoid
bioavailability when taken with a grapefruit juice or increased
full meal. Grapefruit juice results itraconazole dose might be
in 30% decrease in itraconazole necessary.
AUC.
Itraconazole (solution) 31% increase in AUC when taken Take without food if possible.
under fasting conditions.
---------------------------------------------------------------------------------------------
===============================================================================================
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TABLE 4. Effects of medications on drugs used to prevent opportunistic infections
=========================================================================================================
Affected drug Interacting drug(s) Mechanism/Effect Recommendation
-------------------------------------------------------------------------------------------------------
Atovaquone Rifampin Induction of Concentrations might
metabolism - not be therapeutic;
decreased drug levels avoid combination or
increase atovaquone
dose.
Clarithromycin Ritonavir Inhibition of No adjustment needed
metabolism - in normal renal
increased drug levels function; adjust if
by 77% creatinine clearance is
<30.
Clarithromycin Nevirapine Induction of Effect on
metabolism - Mycobacterium avium
decrease in prophylaxis might be
clarithromycin area decreased; monitor
under the curve (AUC) closely.
by 35%, increase in
AUC of 14-OH
clarithromycin by 27%
Ketoconazole Antacids, didanosine, Increase in gastric pH Avoid use of
H2-blockers, proton that impairs ketoconazole with
pump inhibitors absorption of pH-raising agents or
ketoconazole use alternative
antifungal drug.
Quinolone antibiotics Didanosine, antacids, Chelation that results Administer interacting
(ciprofloxacin, iron products, calcium in marked decrease in drug at least 2 hours
levofloxacin, ofloxacin) products, sucralfate quinolone drug levels after quinolone.
Rifabutin Fluconazole Inhibition of Monitor for rifabutin
metabolism - marked toxicity such as uveitis,
increase in rifabutin nausea, neutropenia.
drug levels
Rifabutin Efavirenz Induction of Increase rifabutin dose
metabolism - to 450 mg daily.
significant decrease in
rifabutin AUC
Rifabutin Ritonavir, saquinavir, Inhibition of Contraindicated with
indinavir, nelfinavir, metabolism -- marked hard-gel saquinavir
amprenavir, increase in rifabutin (caution also advised
delavirdine drug levels with soft-gel
saquinavir) and
delavirdine; use
1/2 dose (150 mg daily),
with indinavir,
nelfinavir, amprenavir;
1/4 dose (150 mg every
other day) with
ritonavir.
-------------------------------------------------------------------------------------------------------
=========================================================================================================
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TABLE 5. Effects of opportunistic infection medications on drugs
commonly administered to persons infected with human immunodeficiency virus
===================================================================================================
Affected drug Interacting drug(s) Mechanism/Effect Recommendation
-------------------------------------------------------------------------------------------------
Indinavir, saquinavir, Rifampin Induction of Avoid concomitant use.
ritonavir, nelfinavir, metabolism -- marked
amprenavir decrease in protease
inhibitor drug levels
Delavirdine, Rifampin Induction of Avoid concomitant use.
nevirapine, efavirenz metabolism -- marked
decrease in drug levels
Saquinavir (hard-gel), Rifabutin Induction of Avoid concomitant use.
delavirdine metabolism -- marked
decrease in drug levels
Terfenadine, Ketoconazole Inhibition of Cardiotoxic
astemizole, cisapride Itraconazole metabolism life-threatening effects
Fluconazole possible; avoid
Clarithromycin concomitant use.
Didanosine (ddI) Ganciclovir Increases ddI area Clinical significance
under the curve (AUC) unknown; monitor for
by approximately 100% ddI-related adverse
effects.
-------------------------------------------------------------------------------------------------
===================================================================================================
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TABLE 6. Adverse effects of opportunistic infection medications used in the
management of human immunodeficiency virus infect
-----------------------------------------------------------------------------------
Bone marrow suppression Cidofovir, dapsone, ganciclovir, pyrimethamine, rifabutin,
sulfadiazine, trimethoprim-sulfamethoxazole, trimetrexate
Diarrhea Atovaquone, clindamycin
Hepatotoxicity Clarithromycin, fluconazole, isoniazid, itraconazole,
ketoconazole, pyrazinamide, rifabutin, rifampin
Nephrotoxicity Amphotericin B, cidofovir, foscarnet, pentamidine
Ocular effects Cidofovir, ethambutol, rifabutin
Pancreatitis Pentamidine, trimethoprim-sulfamethoxazole
Peripheral neuropathy Isoniazid
Skin rash Atovaquone, dapsone, sulfadiazine,
trimethoprim-sulfamethoxazole
-----------------------------------------------------------------------------------
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TABLE 7. Dosages of drugs for primary prevention or maintenance therapy for persons
with opportunistic infections and renal insufficiency
==========================================================================================================
CrCl
Drug Normal Dosage (ml/min/1.73m²) Adjusted dose
-----------------------------------------------------------------------------------------------
Acyclovir 200 mg po t.i.d. <10 200 mg q. 12 h
400 mg po q. 12 h <10 200 mg q. 12 h
800 mg po q. 4 h 10-25 800 mg q. 8 h
800 mg po q. 4 h <10 800 mg q. 12 h
Cidofovir 5 mg/kg iv q.o.w. Increase in serum
(with probenecid) creatinine of
0.3-0.4 above 3 mg/kg
baseline
Increase in serum
creatinine of
0.5 above Discontinue.
baseline or
3+ proteinuria
Ciprofloxacin 500 mg po q. 12 h 30-50 250-500 mg q. 12 h
<30 250-500 mg q. 18 h
Clarithromycin 500 mg b.i.d. <30 1/2 dose (or double interval)
Famciclovir 500 mg po q. 12 h 20-39 250 mg q. 12 h
<20 250 mg q. 24 h
Fluconazole 50-400mg po q.d. 10-50 1/2 dose
<10 1/4 dose
Dialysis Full dose after dialysis
Foscarnet 90-120 mg/kg CrCI* Low dose High dose
iv q.d. ------- --------------- ---------------
>1.4 90 mg q. 24 h 120 mg q. 24 h
1.0-1.4 70 mg q. 24 h 90 mg q. 24h
0.8-1.0 50 mg q. 24 h 65 mg q. 24 h
0.6-0.8 80 mg q. 48 h 105 mg q. 48 h
0.5-0.6 60 mg q. 48 h 80 mg q. 48 h
0.4-0.5 50 mg q. 48h 65 mg q. 48 h
<0.4 Not recommended Not recommended
Ganciclovir Oral: 50-69 1,500 mg q.d. or 500 mg t.i.d.
1 gram po t.i.d. 25-49 1,000 mg q.d. or 500 mg b.i.d.
10-24 500 mg q.d.
<10 500 mg t.i.w. after dialysis
IV:
5 mg/kg q.d. or 50-69 2.5 mg/kg q. 24 h
6 mg/kg q.d. x 25-49 1.25 mg/kg q. 24 h
5 days/week 10-24 0.625 mg/kg q. 48 h
<10 0.625 mg/kg t.i.w.
Trimethoprim- 1 DS q.d. <30 1/2 dose
sulfamethoxazole 1 DS t.i.w.
1 SS q.d.
-----------------------------------------------------------------------------------------------
ABBREVIATIONS: b.i.d. = twice daily; CrCl = creatinine clearance; DS = double-strength tablet; iv =
intravenous; l.d. = loading dose; q.d. = daily; q.o.w. = every other week; SS = single-strength tablet;
t.i.d. = three times daily; t.i.w. = three times a week.
* Creatinine clearance for foscarnet is expressed as ml/min/kg.
==========================================================================================================
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TABLE 8. Wholesale acquisition costs of agents recommended for the prevention of
opportunistic infections in adults infected with human immunodeficiency virus
==============================================================================================================
Opportunistic Annual cost
pathogen Drug/vaccine Dose per patient
------------------------------------------------------------------------------------------------
Pneumocystis carinii Trimethoprim- 160/800 mg q.d. $60
sulfamethoxazole
Dapsone 100 mg q.d. $72
Aerosolized pentamidine 300 mg q.m. $1,185
Atovaquone 1500 mg q.d. $10,647
Mycobacterium Clarithromycin 500 mg b.i.d. $2,347
avium complex Azithromycin 1,200 mg q.w. $1,635
Rifabutin 300 mg q.d. $3,352
Cytomegalovirus Ganciclovir (po) 1,000 mg t.i.d. $17,269
Ganciclovir implant* $5,000
Ganciclovir (iv) 5mg/kg q.d. $9,113
Foscarnet (iv) 90-120 mg/kg q.d. $27,960-36,770
Cidofovir (iv) 375 mg q.o.w. $19,812
Fomivirsen (intravitreal) 1 vial every 4 wks $12,000
Mycobacterium Isoniazid+ 300 mg q.d. $23
tuberculosis Rifampin 600 mg q.d. $1,540
Pyrazinamide 1,500 mg q.d. $1,005
Ethambutol 900 mg q.d. $1,527
Fungi Fluconazole 200 mg q.d. $4,267
Itraconazole capsules 200 mg q.d. $4,893
Itraconazole solution 200 mg q.d. $5,129
Ketoconazole 200 mg q.d. $1,230
Herpes simplex virus Acyclovir 400 mg b.i.d. $1,300
Famciclovir 500 mg b.i.d. $4,826
Valacyclovir 500 mg b.i.d. $1,435
Toxoplasma gondii Pyrimethamine 50 mg q.w. $45
Leucovorin 25 mg q.w. $1,248
Sulfadiazine 500 mg q.i.d. $1,421
Streptococcus 23-valent pneumococcal 0.5 ml im x 1 $13
pneumoniae vaccine
Influenza virus Influenza vaccine 0.5 ml im x 1 $5
Hepatitis B virus Recombinant hepatitis B 10-20µg im x 3 $195
Hepatitis A virus Hepatitis A vaccine 1.0 ml im x 2 $120
Bacterial infections G-CSF 300 µg t.i.w. $25,780
Varicella zoster virus VZIG 5 vials (6.25 ml) $560
------------------------------------------------------------------------------------------------
ABBREVIATIONS: b.i.d. = twice daily; G-CSF = granulocyte-colony-stimulating factor; iv = intravenous; im =
intramuscular; po = by mouth; q.d. = daily; q.o.w. = every other week; q.w. = once a week; ; t.i.d. = three
times daily; t.i.w. = three times a week; VZIG = varicella zoster immune globulin.
* Implant generally lasts 6-9 months.
+ Cost for 9 months of therapy.
Source: Medical Economics. Drug topics red book. Montvale, New Jersey: Medical Economics Inc., 1999.
==============================================================================================================
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TABLE 9. Immunologic categories for human immunodeficiency virus-infected
children based on age-specific CD4+ T-lymphocyte counts and percentage of total
lymphocytes*
=============================================================================================
Age
----------------------------------------------------
<=12 months 1-5 years 6-12 years
----------------- --------------- ---------------
Immunologic category cells/µL (%) cells/µL (%) cells/µL (%)
------------------------------------------------------------------------------------------
1. No evidence of suppression >=1,500 (>=25) >=1,000 (>=25) >=500 (>=25)
2. Evidence of moderate
suppression 750-1,499 (15-24) 500-999 (15-24) 200-499 (15-24)
3. Severe suppression <750 (<15) <500 (<15) <200 (<15)
------------------------------------------------------------------------------------------
* Adapted from CDC. 1994 revised classification system for human immunodeficiency virus
infection in children less than 13 years of age. MMWR 1994;43(No. RR-12).
=============================================================================================
Return to top. Table 10 To print large tables and graphs users may have to change their printer settings to landscape and use a small font size. TABLE 10. Recommended immunization schedule for human immunodeficiency virus-infected children* Return to top. Table 11 To print large tables and graphs users may have to change their printer settings to landscape and use a small font size.
TABLE 11. Prophylaxis to prevent first episode of opportunistic disease in infants and
children infected with human immunodeficiency virus
==================================================================================================================
Preventive Regimens
----------------------------------------------------------------------------------
Pathogen Indication First Choice Alternatives
-----------------------------------------------------------------------------------------------------------------
I. Strongly recommended as standard of care
Pneumocystis carinii* HIV-infected or Trimethoprim- Dapsone (children
HIV-indeterminate, sulfamethoxazole aged >=1 mo), 2 mg/kg
infants aged 1-12 mo; (TMP-SMZ), 150/750 (max 100 mg) po q.d.
mg/m²/d in 2 divided or 4 mg/kg (max
HIV-infected children doses po t.i.w. 200 mg) po q.w. (CII);
aged 1-5 yr with CD4+ on consecutive days (AII) aerosolized
count <500/µL or CD4+ pentamidine (children
percentage <15%; Acceptable alternative aged >=5 yr), 300 mg
dosage schedules: (AII) q.m. via Respirgard
HIV-infected children II(TM) nebulizer (CIII);
aged 6-12 yr with • Single dose po atovaquone (children
CD4+ count <200/µL or t.i.w. on aged 1-3 mo. and
CD4+percentage <15% consecutive days; >24 mo., 30 mg/kg po
q.d.; children aged
• 2 divided doses po 4-24 mo., 45 mg/kg po
q.d.; 2 divided q.d.) (CII)
doses po t.i.w. on
alternate days
Mycobacterium
tuberculosis+
Isoniazid-sensitive TST reaction, >=5mm Isoniazid 10-15 mg/kg Rifampin,
or prior positive TST (max 300 mg) po q.d. 10-20 mg/kg (max
result without x 9 mo (AII) or 600 mg) po q.d. x
treatment or contact 20-30 mg/kg (max 4-6 mo (BIII)
with case of active 900 mg) po b.i.w. x 9
tuberculosis mo (BIII)
Isoniazid-resistant Same as above; high Rifampin, 10-20 Uncertain
probability of mg/kg (max 600 mg)
exposure to po q.d. x 4-6 mo (BIII)
isoniazid-resistant
tuberculosis
Multidrug-(isoniazid Same as above; high Choice of drugs None
and rifampin) probability of requires consultation
resistant exposure to with public health
multidrug-resistant authorities
tuberculosis
Mycobacterium avium For children aged Clarithromycin, Azithromycin, 5 mg/kg
complex+ >=6 yrs, CD4+ count 7.5 mg/kg (max (max 250 mg) po q.d.
<50/µL; aged 2-6 yrs, 500 mg) po b.i.d. (AII), (AII); children aged
CD4+ count <75/µL; or azithromycin, >=6 yrs, rifabutin,
aged 1-2 yrs, CD4+ 20 mg/kg (max 300 mg po q.d. (BI)
count <500/µL; aged 1,200 mg) po q.w. (AII)
<1 yr, CD4+ count
<750/µL
Varicella zoster virus& Significant exposure Varicella zoster None
to varicella or shingles immune globulin
with no history of (VZIG), 1 vial
chickenpox or shingles (1.25 mL)/10 kg (max
5 vials) im,
administered <=96 hrs
after exposure, ideally
within 48 hrs (AII)
Vaccine-preventable HIV exposure/infection Routine None
pathogens@ immunizations
(see Table 10)
II. Generally recommended
Toxoplasma gondii** IgG antibody to TMP-SMZ, Dapsone (children
Toxoplasma 150/750 mg/m²/d in 2 aged >=1 mo), 2 mg/kg
and severe divided doses po q.d. or 15 mg/m² (max
immunosuppression (BIII) 25 mg) po q.d. plus
pyrimethamine,
1 mg/kg po q.d. plus
leucovorin, 5 mg po
every 3 days (BIII)
Atovaquone, (aged
1-3 mo. and >24 mo.,
30 mg/kg po q.d.;
aged 14-24 mo.
45 mg/kg po q.d.) (CIII)
Varicella zoster virus@ HIV-infected children Varicella zoster None
who are vaccine (see vaccine-
asymptomatic and not preventable
immunosuppressed pathogens section of
this table) (BII)
Influenza virus@ All patients (annually, Influenza vaccine (see Rimantadine or
before influenza vaccine-preventable amantadine (during
season) pathogens section of outbreaks of influenza
this table) (BIII) A); aged 1-9 yr,
5 mg/kg in 2 divided
doses po q.d.; aged
>=10 yr, use adult
doses (CIII)
III. Not recommended for most children; indicated for use only in unusual circumstances
Invasive bacterial Hypogamma- IVIG (400mg/kg every None
infections++ globulinemia (i.e., IgG 2-4 wks) (AI)
<400 mg/dL)
Cryptococcus Severe Fluconazole, 3-6 Itraconazole,
neoformans immunosuppression mg/kg po q.d. (CII) 2-5 mg/kg po every
12-24 h (CII)
Histoplasma Severe Itraconazole, None
capsulatum immunosuppression, 2-5 mg/kg po every
endemic geographic 12-24 h (CIII)
area
Cytomegalovirus CMV antibody Oral ganciclovir None
(CMV)&& positivity and severe 30 mg/kg po t.i.d. (CII)
immunosuppression
-----------------------------------------------------------------------------------------------------------------
NOTES: Information included in these guidelines might not represent Food and Drug Administration (FDA)
approval or approved labeling for the particular products or indications in question. Specifically, the terms
"safe" and "effective" might not be synonymous with the FDA-defined legal standards for product approval.
The Respirgard II(TM) nebulizer is manufactured by Marquest, Englewood, Colorado. Letters and Roman
numerals in parentheses after regimens indicate the strength of the recommendation and the quality of the
evidence supporting it (see Box, page 3).
ABBREVIATIONS: b.i.w. = twice a week; IVIG = intravenous immune globulin; q.d. = daily; q.m. = monthly;
t.i.d. = three times a day; t.i.w. = three times a week.
* Daily TMP-SMZ reduces the frequency of some bacterial infections. TMP-SMZ, dapsone-pyrimethamine,
and possibly atovaquone (with or without pyrimethamine) appear to protect against toxoplasmosis,
although data have not been prospectively collected. When compared with weekly dapsone, daily
dapsone is associated with lower incidence of Pneumocystis carinii pneumonia (PCP) but higher
hematologic toxicity and mortality (McIntosh K, Cooper E, Xu J, et al. Toxicity and efficacy of daily vs.
weekly dapsone for prevention of Pneumocystis carinii pneumonia in children infected with HIV. Ped
Infect Dis J 1999;18:432-9). The efficacy of parenteral pentamidine (e.g., 4 mg/kg q 2-4 wks) is
controversial. Patients receiving therapy for toxoplasmosis with sulfadiazine-pyrimethamine are
protected against PCP and do not need TMP-SMZ.
+ Significant drug interactions might occur between rifamycins (rifampin and rifabutin) and protease
inhibitors and nonnucleoside reverse transcriptase inhibitors. Consult a specialist.
& Children routinely being administered intravenous immune globulin (IVIG) should receive VZIG if the
last dose of IVIG was administered >21 days before exposure.
@ HIV-infected and HIV-exposed children should be immunized according to the childhood immunization
schedule in this report (Table 10), which has been adapted from the January-December 1999 schedule
recommended for immunocompetent children by the Advisory Committee on Immunization Practices,
the American Academy of Pediatrics, and the American Academy of Family Physicians. This schedule
differs from that for immunocompetent children in that inactivated poliovirus vaccine (IPV) replaces oral
poliovirus vaccine (OPV), and vaccination against influenza (BIII) and Streptococcus pneumoniae (BII)
should be offered. MMR should not be administered to severely immunocompromised children (DIII).
Vaccination against varicella is indicated only for asymptomatic nonimmunosuppressed children (BII),
and rotavirus vaccine is contraindicated in all HIV-infected children (EIII). Once an HIV-exposed child is
determined not to be HIV infected, the schedule for immunocompetent children applies.
** Protection against toxoplasmosis is provided by the preferred antipneumocystis regimens and possibly
by atovaquone. Atovaquone may be used with or without pyrimethamine. Pyrimethamine alone probably
provides little, if any, protection (for definition of severe immunosuppression, see Table 9).
++ Respiratory syncytial virus (RSV) IVIG (750 mg/kg), not monoclonal RSV antibody, may be substituted
for IVIG during the RSV season to provide broad antiinfective protection, if this product is available.
&& Oral ganciclovir results in reduced CMV shedding in CMV-infected children. Acyclovir is not protective
against CMV.
==================================================================================================================
Return to top. Table 12 To print large tables and graphs users may have to change their printer settings to landscape and use a small font size.
TABLE 12. Prophylaxis to prevent recurrence of opportunistic disease (after
chemotherapy for acute disease) in HIV-infected infants and children
===============================================================================================================
Preventive Regimens
----------------------------------------------------------------------------
Pathogen Indication First Choice Alternative
------------------------------------------------------------------------------------------------------
I. Recommended for life as standard of care
Pneumocystis carinii Prior P. carinii TMP-SMZ, 150/750 Dapsone (children
pneumonia mg/m² /d in 2 divided aged >=1 mo), 2 mg/kg
doses po t.i.w. on (max 100 mg) po q.d.
consecutive days (AII) or 4 mg/kg (max
200 mg) po q.w. (CII);
Acceptable alternative aerosolized
schedules for same pentamidine (children
dosage: (AII) aged >=5 yrs), 300 mg
q.m. via Respirgard II(TM)
Single dose po t.i.w. on nebulizer (CIII);
consecutive days; atovaquone (aged
2 divided doses po q.d; 1-3 mo. and >24 mo.,
2 divided doses po 30 mg/kg po q.d.; aged
t.i.w. on alternate days 4-24 mo., 45 mg/kg po
q.d.) (CII)
Toxoplasma gondii* Prior toxoplasmic Sulfadiazine, Clindamycin,
encephalitis 85-120 mg/kg/d in 20-30 mg/kg/d in
2-4 divided doses po 4 divided doses po q.d.
q.d. plus plus pyrimethamine,
pyrimethamine, 1 mg/kg po q.d. plus
1 mg/kg or 15 mg/m² leucovorin, 5 mg po
(max 25 mg) po q.d. every 3 days (BI)
plus leucovorin, 5 mg
po every 3 days (AI)
Mycobacterium avium Prior disease Clarithromycin, Azithromycin, 5 mg/kg
complex+ 7.5 mg/kg (max (max 250 mg) po q.d.
500 mg) po b.i.d. (AII) (AII) plus ethambutol,
plus ethambutol, 15 mg/kg (max
15 mg/kg (max 900 mg) po q.d. (AII);
900 mg) po q.d. (AII); with or without
with or without rifabutin, 5 mg/kg (max
rifabutin, 5 mg/kg (max 300 mg) po q.d. (CII)
300 mg) po q.d. (CII)
Cryptococcus Documented disease Fluconazole, 3-6 mg/kg Amphotericin B,
neoformans po q.d. (AII) 0.5-1.0 mg/kg iv
1-3x/week (AI);
itraconazole, 2-5
mg/kg po every 12-24h
(BII).
Histoplasma Documented disease Itraconazole, Amphotericin B,
capsulatum 2-5 mg/kg po every 1.0 mg/kg iv q.w. (AIII)
12-48 h (AIII)
Coccidioides immitis Documented disease Fluconazole, 6 mg/kg Amphotericin B,
po q.d. (AIII) 1.0 mg/kg iv q.w. (AIII);
itraconazole,
2-5 mg/kg po every
12-48 h (AIII)
Cytomegalovirus Prior end-organ Ganciclovir, 5 mg/kg iv (For retinitis)
disease q.d.; or foscarnet, Ganciclovir
90-120 mg/kg iv q.d. sustained-release
(AI) implant every 6-9 mo.
plus ganciclovir,
30 mg/kg po t.i.d. (BIII)
Salmonella species Bacteremia TMP-SMZ, Antibiotic
(non-typhi)& 150/750 mg/m² in chemoprophylaxis
2 divided doses po q.d. with another active
for several months (CIII) agent (CIII)
II. Recommended only if subsequent episodes are frequent or severe
Invasive bacterial >2 infections in TMP-SMZ, Antibiotic
infections@ 1-year period 150/750 mg/m², in chemoprophylaxis
2 divided doses po q.d. with another active
(BI); or IVIG, 400 mg/kg agent (BIII)
every 2-4 wks. (BI)
Herpes simplex virus Frequent/severe Acyclovir, 80 mg/kg/d
recurrences in 3-4 divided doses
po q.d. (AII)
Candida Frequent/severe Fluconazole, 3-6 mg/kg
(oropharyngeal) recurrences po q.d. (CIII)
Candida (esophageal) Frequent/severe Fluconazole, 3-6 mg/kg Itraconazole solution,
recurrences po q.d. (BIII) 5 mg/kg po q.d. (CIII);
ketoconazole,
5-10 mg/kg po every
24-12h (CIII)
------------------------------------------------------------------------------------------------------
NOTES: Information included in these guidelines might not represent Food and Drug Administration (FDA)
approval or approved labeling for the particular products or indications in question. Specifically, the terms
"safe" and "effective" might not be synonymous with the FDA-defined legal standards for product approval.
The Respirgard II(TM) nebulizer is manufactured by Marquest, Englewood, Colorado. Letters and Roman
numerals in parentheses after regimens indicate the strength of the recommendations and the quality of
evidence supporting it (see Box, page 3).
ABBREVIATIONS: IVIG = intravenous immune globulin; po = by mouth; q.d. = daily; q.m. = monthly; q.w. =
weekly; t.i.d. = three times a day; t.i.w. = three times a week; and TMP-SMZ = trimethoprim-sulfamethoxazole.
* Only pyrimethamine plus sulfadiazine confers protection against PCP as well as toxoplasmosis. Although
the clindamycin plus pyrimethamine regimen is the preferred alternative in adults, it has not been tested
in children. However, these drugs are safe and are used for other infections.
+ Significant drug interactions might occur between rifabutin and protease inhibitors and nonnucleoside
reverse transcriptase inhibitors. Consult an expert.
& Drug should be determined by susceptibilities of the organism isolated. Alternatives to TMP-SMZ include
ampicillin, chloramphenicol, or ciprofloxacin. However, ciprofloxacin is not approved for use in persons
aged <18 years; therefore, it should be used in children with caution and only if no alternatives exist.
@ Antimicrobial prophylaxis should be chosen based on the microorganism and antibiotic sensitivities. TMP-
SMZ, if used, should be administered daily. Providers should be cautious about using antibiotics solely for
this purpose because of the potential for development of drug-resistant microorganisms. IVIG might not
provide additional benefit to children receiving daily TMP-SMZ but may be considered for children who
have recurrent bacterial infections despite TMP-SMZ prophylaxis. Choice of antibiotic prophylaxis vs. IVIG
should also involve consideration of adherence, ease of intravenous access, and cost. If IVIG is used,
respiratory syncytial virus (RSV) IVIG (750 mg/kg), not monoclonal RSV antibody, may be substituted for
IVIG during the RSV season to provide broad antiinfective protection, if this product is available.
===============================================================================================================
Return to top. Table 13 To print large tables and graphs users may have to change their printer settings to landscape and use a small font size.
TABLE 13. Criteria for discontinuing and restarting opportunistic infection prophylaxis
for adults with human immunodeficiency virus infection*
===================================================================================================
Criteria for Discontinuing Prophylaxis
----------------------------------------------- Criteria for Restarting
Opportunistic Illness Primary Secondary Prophylaxis
-------------------------------------------------------------------------------------------------
Pneumocystis carinii CD4+ >200 cells/µL for No criteria Same as criteria for
pneumonia >3-6 months (CII) recommended for initiating (CIII)
stopping
Disseminated CD4+ >100 cells/µL for No criteria Same as criteria for
Mycobacterium avium >3-6 months; recommended for initiating (CIII)
complex sustained suppression stopping
of HIV plasma RNA (CII)
Toxoplasmosis No criteria No criteria Not applicable
recommended for recommended for
stopping stopping
Cryptococcosis Not applicable No criteria Not applicable
recommended for
stopping
Histoplasmosis Not applicable No criteria Not applicable
recommended for
stopping
Coccidioidomycosis Not applicable No criteria Not applicable
recommended for
stopping
Cytomegalovirus Not applicable • CD4+ >100-150 Restart maintenance
retinitis cells/µL for when CD4+
>3-6 months <50-100 cells/µL (CIII).
• Durable
suppression of HIV
plasma RNA
• Nonsight-
threatening lesion
• Adequate vision in
contralaterial eye
• Regular
Ophthalmic
examination (CIII)
-------------------------------------------------------------------------------------------------
* The safety of discontinuing prophylaxis in children whose CD4+ counts have increased in
response to highly active antiretroviral therapy has not been studied.
===================================================================================================
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