1999 USPHS/IDSA Guidelines for the Prevention of Opportunistic Infections in Persons Infected with Human Immunodeficiency Virus
Journal: Annals of Internal Medicine (1999)

MMWR Supplements7 December 19991999 USPHS/IDSA Guidelines for the Prevention of Opportunistic Infections in Persons Infected with Human Immunodeficiency VirusFREEUSPHS/IDSA Prevention of Opportunistic Infections Working GroupUSPHS/IDSA Prevention of Opportunistic Infections Working GroupSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-131-11-199912070-00022 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail In August 1999, agencies of the U.S. Public Health Service (USPHS), in collaboration with the Infectious Diseases Society of American (IDSA), published 1999 Guidelines for the Prevention of Opportunistic Infections in Persons Infected with Human Immunodeficiency Virus (HIV) (1). These guidelines are an update of those prepared in 1995 and 1997 and published in several venues, including Annals of Internal Medicine (2, 3). They are intended primarily for health care providers who care for HIV-infected persons and are reproduced here in an effort to reach and as a service to all internists who care for HIV-infected patients.Single copies of the 1999 USPHS/IDSA guidelines can be obtained from the AIDS Treatment Information Service (ATIS) by calling 800-448-0440, 301-217-0023 (international), or 800-243-7012 (TYY) or by downloading the document from the ATIS Web site at www.hivatis.org.References1. USPHS/IDSA Prevention of Opportunistic Infections Working Group. 1999 USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus. MMWR Morb Mortal Wkly Rep. 1999; 48(RR-10):1-66.2. USPHS/IDSA Prevention of Opportunistic Infections Working Group. USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus: a summary. Ann Intern Med. 1996; 124:348-68.3. USPHS/IDSA Prevention of Opportunistic Infections Working Group. 1997 USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus. Ann Intern Med. 1997; 127:922-46.Members of the USPHS/IDSA Prevention of Opportunistic Infections Working GroupThe working group was chaired by Henry Masur, MD, National Institutes of Health, Bethesda, MD; Jonathan E. Kaplan, MD, Centers for Disease Control and Prevention, Atlanta; and King K. Holmes, MD, PhD, University of Washington, Seattle.Members of the group included Beverly L. Alston, MD (National Institutes of Health, Bethesda, MD); Neil Ampel, MD (University of Arizona, Tucson); Jean R. Anderson, MD (Johns Hopkins University, Baltimore); A. Cornelius Baker (National Association of People with AIDS, Washington, DC); David Barr (Forum for Collaborative HIV Research, Washington, DC); John G. Bartlett, MD (Johns Hopkins University, Baltimore); John E. Bennett, MD (National Institutes of Health, Bethesda, MD); Constance A. Benson, MD (University of Colorado, Denver); Samual A. Bozzette, MD (University of California, San Diego); Richard E. Chaisson, MD (Johns Hopkins University, Baltimore); Clyde S. Crumpacker, MD (Harvard Medical Center, Boston); Judith S. Currier, MD, MSc (University of California-Los Angeles Medical Center, Los Angeles); Lawrence Deyton, MD, MSPH (U.S. Department of Veterans Affairs, Washington, DC); W. Lawrence Drew, MD, PhD (Mt. Zion Medical Center, University of California-San Francisco, San Francisco); William R. Duncan, PhD (National Institutes of Health, Bethesda, MD); Robert W. Eisinger, PhD (National Institutes of Health, Bethesda, MD); Wafaa El-Sadr, MD, MPH, MPA (Harlem Hospital, New York); Judith Feinberg, MD (Holmes Hospital, Cincinnati); Kenneth A. Freedberg, MD, MSc (Boston University School of Medicine, Boston); Hansjakob Furrer, MD (University Hospital, Berne, Switzerland); John W. Gnann Jr., MD (University of Alabama, Birmingham); Mark J. Goldberger, MD, MPH (U.S. Food and Drug Administration, Rockville, MD); Sue Goldie, MD, PhD (Harvard School of Public Health, Boston); Eric P. Goosby, MD (U.S. Department of Health and Human Services, Washington, DC); Peter A. Gross, MD (Hackensack Medical Center, Hackensack, NJ); Richard Hafner, MD (National Institutes of Health, Bethesda, MD); Diane Havlir, MD (University of California, San Diego); Thomas M. Hooton, MD (Harborview Medical Center, Seattle); Douglas A. Jabs, MD (Johns Hopkins University, Baltimore); Mark A. Jacobson, MD (University of California, San Francisco); Edward Janoff, MD (Veterans Administration Medical Center, Minneapolis); Mari Kitahata, MD, PhD (University of Washington, Seattle); Joseph V. Kovacs, MD (National Institutes of Health, Bethesda, MD); Catherine Leport, MD (Hospital Bichat-Claude Bernard, Paris); Myron J. Levin, MD (University of Colorado Health Science Center, Denver); Juan C. Lopez, MD (Hospital Universatario Gregorio Maranon, Madrid); Michael Marco (Treatment Action Group, New York); Douglas L. Mayers, MD (Henry Ford Hospital, Detroit); David A. Melnick, MD (Kaiser Permanente, Springfield, VA); Lynne M. Mofenson, MD (National Institutes of Health, Bethesda, MD); Julio S.G. Montaner, MD (St. Paul's Hospital, Vancouver); Richard Moore, MD (Johns Hopkins University, Baltimore); James Neaton, PhD (University of Minnesota, Minneapolis); Charles Nelson (National Association of People with AIDS, Washington, DC); Joseph F. O'Neill, MD, MS, MPH (Health Resources and Services Administration, Rockville, MD); Joel Palefsky, MD (University of California, San Francisco); Alice Pau, PharmD (National Institutes of Health, Bethesda, MD); John P. Phair, MD (Northwestern University, Chicago); Stephen Piscitelli, PharmD (National Institutes of Health, Bethesda, MD); Michael A. Polis, MD, MPH (National Institutes of Health, Bethesda, MD); Thomas C. Quinn, MD (Johns Hopkins Hospital, Baltimore); Peter Reiss, MD, PhD (University of Amsterdam, Amsterdam); David Rimland, MD (Veterans Administration Medical Center, Atlanta); Cynthia L. Sears, MD (Johns Hopkins University, Baltimore); Leonard Seeff, MD (National Institutes of Health, Bethesda, MD); Kent A. Sepkowitz, MD (Memorial Sloan-Kettering Cancer Center, New York); Thomas G. Slama, MD (National Foundation for Infectious Diseases, Indianapolis); Elaine M. Sloand, MD (National Institutes of Health, Bethesda, MD); Stephen A. Spector, MD (University of California, La Jolla); David L. Thomas, MD, MPH (Johns Hopkins University, Baltimore); Russell B. Van Dyke, MD (Tulane School of Medicine, New Orleans, LA); D. Heather Watts, MD (National Institutes of Health, Bethesda, MD); L. Joseph Wheat, MD (Indiana University School of Medicine, Indianapolis); Scott M. Whitcup, MD (National Institutes of Health, Bethesda, MD); Paige Williams, PhD (Harvard School of Public Health, Boston); Thomas C. Wright Jr., MD (Columbia University College of Physicians and Surgeons, New York).Participants from the Centers for Disease Control and Prevention, Atlanta, included Kenneth G. Castro, MD, Kevin M. DeCock, MD, DTM&H, Scott F. Dowell, MD, MPH, Mark S. Dworkin, MD, MPHTM, Clare Dykewicz, MD, MPH, Tedd Ellerbrock, MD, Rana Hajjeh, MD, Scott Holmberg, MD, MPH, David R. Holtgrave, PhD, Harold W. Jaffe, MD, Jeffrey L. Jones, MD, Dennis D. Juranek, DVM, MSc, Eric Mast, MD, MPH, Thomas Navin, MD, Phil E. Pellett, PhD, William C. Reeves, MD, MPH, John A. Stewart, MD, and M. Elsa Villarino, MD, MPH.This report was prepared by Jonathan E. Kaplan, MD (Division of AIDS, STD, and TB Laboratory Research, National Center for Infectious Diseases and Division of HIV/AIDS Prevention—Surveillance and Epidemiology, National Center for HIV, STD, and TB Prevention) in collaboration with Henry Masur, MD (National Institutes of Health) and King K. Holmes, MD, PhD (University of Washington).PREFACEIn 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 MMWR (4), Clinical Infectious Diseases (5), Annals of Internal Medicine (6), 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 (MAC) disease, and bacterial infections. Trimethoprim-sulfamethoxazole (TMP-SMZ) was shown to reduce the incidence not only 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 (HAARTs) 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 (HHV-8) and hepatitis C virus (HCV). 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 RECOMMENDATIONSPrimary changes in the disease-specific recommendations that follow includeThe addition of statements concerning discontinuation of prophylaxis against specific OIs when the CD4+ T-lymphocyte count increases in response to HAART.New recommendations regarding HHV-8 and HCV.New recommendations concerning injection drug users.New recommendations about short-course chemoprophylaxis against tuberculosis in HIV-infected persons with positive tuberculin skin tests (TSTs).Changes in secondary prophylaxis (chronic maintenance therapy) recommended to prevent the recurrence of MAC and cytomegalovirus (CMV) disease.Caution against using fluconazole during pregnancy.Statements concerning the use of varicella and rotavirus vaccines among HIV-infected infants.These guidelines developed by the OI Working Group were made available for public comment through announcements in the Federal Register and 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 REPORTFor 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 (Table 1) (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.Table 1. System Used To Rate the Strength of Recommendations and Quality of Supporting Evidence Because of their length and complexity, the rest of the tables and figure in this report are grouped together, following the references. The tables and figure appear in the following order: dosages for prophylaxis to prevent first episode of opportunistic disease in HIV-infected adults and adolescents (Table 2); dosages for prophylaxis to prevent recurrence of opportunistic disease in HIV-infected adults and adolescents (Table 3); effects of food on drugs used to treat OIs (Table 4); effects of medications on drugs used to treat OIs (Table 5); effects of OI medications on drugs commonly administered to HIV-infected persons (Table 6); adverse effects of drugs used to manage HIV infection (Table 7); dosages of drugs for prevention of OIs for persons with renal insufficiency (Table 8); costs of agents recommended for the prevention of OIs in adults with HIV infection (Table 9); immunologic categories for HIV-infected children (Table 10); immunization schedule for HIV-infected children (Figure); 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 the text.Table 2. Prophylaxis To Prevent First Episode of Opportunistic Disease in Adults and Adolescents Infected with Human Immunodeficiency Virus Table 3. Prophylaxis To Prevent Recurrence of Opportunistic Disease (after Chemotherapy for Acute Disease) in Adults and Adolescents Infected with Human Immunodeficiency Virus Table 4. Effects of Food on Drugs Used To Prevent Opportunistic Infections Table 5. Effects of Medications on Drugs Used To Prevent Opportunistic Infections Table 6. Effects of Opportunistic Infection Medications on Drugs Commonly Administered to Persons Infected with Human Immunodeficiency Virus Table 7. Adverse Effects of Opportunistic Infection Medications Used in the Management of Human Immunodeficiency Virus Infection Table 8. Dosages of Drugs for Primary Prevention or Maintenance Therapy for Persons with Opportunistic Infections and Renal Insufficiency Table 9. Wholesale Acquisition Costs of Agents Recommended for the Prevention of Opportunistic Infections in Adults Infected with Human Immunodeficiency Virus Table 10. Immunologic Categories for Human Immunodeficiency Virus-Infected Children Based on Age-Specific CD4+ T-Lymphocyte Counts and Percentage of Total Lymphocytes Figure. Recommended immunization schedule for human immunodeficiency virus-infected children. Download figure Download PowerPoint Table 11. Prophylaxis To Prevent First Episode of Opportunistic Disease in Infants and Children Infected with Human Immunodeficiency Virus Table 12. Prophylaxis To Prevent Recurrence of Opportunistic Disease (after Chemotherapy for Acute Disease) in HIV-Infected Infants and Children Table 13. Criteria for Discontinuing and Restarting Opportunistic Infection Prophylaxis for Adults with HIV Infection This report is oriented toward the prevention of specific OIs 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 the Centers for Disease Control and Prevention'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 RECOMMENDATIONSPneumocystis carinii PneumoniaPrevention of Exposure(1) Although some authorities recommend that persons with HIV infection who are at risk for 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 DiseaseInitiation 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 <200/µL (AI) or a history of oropharyngeal candidiasis (AII) (14). Persons who have a CD4+ T-lymphocyte percentage of <14% or history of an 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 >200 but <250 cells/µL also should be considered (BII) (15).(3) 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 <200 cells/µL to >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 >300 cells/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 >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 876 (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 876 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 >200 cells/µL, inadequate numbers of patients have been evaluated to warrant a recommendation to discontinue prophylaxis in such patients.Special ConsiderationsChildren(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 EncephalitisPrevention 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 T. 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 DiseaseInitiation of Primary Prophylaxis(3) Toxoplasma-seropositive patients who have a CD4+ T-lymphocyte count of <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 >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 <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 Considera