Preface

In 1994, the U.S. Public Health Service (USPHS) and the Infectious Diseases Society of America (IDSA) developed guidelines for health-care providers and patients for prevention of opportunistic infections (OIs) in persons infected with human immunodeficiency virus (HIV) (1-3). These guidelines were revised in 1997 and published in 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 recommendations were rated on the basis of the strength of the evidence supporting them, readers were able to assess for themselves the relative importance of each guideline.

Since AIDS was first recognized nearly 20 years ago, remarkable progress has been made in improving the quality and duration of survival 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(TMP-SMZ) 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 modest continuing progress in preventing and treating individual OIs. HAART has reduced the incidence of opportunistic infections and extended life substantially (10). HAART is the most effective approach to preventing opportunistic infections and should be considered for all HIV-infected persons who qualify for such therapy. However, in the United States some patients are not ready or able to take HAART, and others have failed all available HAART regimens. Such patients will benefit from opportunistic infection prophylaxis. In addition, prophylaxis against specific OIs continues to provide survival benefits even among those who have access to HAART.

Because important new data concerning the prevention of opportunistic diseases have emerged since 1997, the USPHS and the IDSA reconvened a working group on March 4-5, 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) in persons whose CD4+ T-lymphocyte counts have increased to above prophylaxis thresholds due to HAART. The meeting also addressed two additional pathogens not previously considered--human herpes virus type 8 (HHV-8) and hepatitis C virus (HCV). However, data concerning the prevention of all common HIV-associated OIs were reviewed. As in earlier editions of the guidelines, factors considered in revising guidelines included 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 toxicities, drug interactions, and the potential for drug resistance to develop.

Consultants 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, as well as the 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:
The primary changes in the disease-specific recommendations that follow include 1) statements concerning discontinuation of prophylaxis against specific OIs when the CD4+ T-lymphocyte count increases in response to HAART, 2) recommendations regarding HHV-8 and HCV, 3) recommendations concerning injection drug users (as requested by some respondents to the 1997 guidelines), 4) recommendations concerning short-course chemoprophylaxis against tuberculosis in HIV-infected persons with positive tuberculin skin tests, 5) changes in secondary prophylaxis (chronic maintenance therapy) recommended to prevent recurrence of Mycobacterium avium complex and cytomegalovirus disease, 6) caution against using fluconazole in the first trimester of pregnancy, and 7) statements concerning use of varicella and rotavirus vaccine in HIV-infected infants.

The guidelines developed by the USPHS/IDSA working group have been made available for public comment by an announcement in the Federal Register and in the MMWR. Pending input and approval, the final document is expected to be endorsed by the USPHS and the IDSA, as well as by numerous other organizations.

How to Use the Information in This Report:
This report presents disease-specific recommendations for prevention of a) exposure to the opportunistic pathogen, b) first episode of disease, and c) disease recurrence. Recommendations are accompanied by a description of the rating system (see Box), drugs and doses for prevention of first episode of disease and disease recurrence in adults (Tables 1A and 1B), drug interactions, toxicities, and dose adjustments required in patients with renal impairment (Tables 2-4), costs of commonly used prophylactic drugs and vaccines (Table 5), categories of immunosuppression in HIV-infected children (Table 6), drugs and doses for prevention of first episode of disease and disease recurrence in children (Tables 7A and 7B), recommendations for prevention of exposure to opportunistic pathogens (Table 8), and a summary of recommendations concerning discontinuation of chemoprophylaxis in persons whose CD4+ T-lymphocyte counts have increased in response to HAART (Table 9). Because of their length and complexity, the tables and figure have been placed at the end of the text, preceding the references.

Recommendations are rated by a revised version of the IDSA rating system (see Box) (11). In this system, a letter rating (letters A through E) signifies the strength of the recommendation for or against this preventive modality; and a Roman numeral (Roman numerals I through III) indicates the quality of the evidence supporting that recommendation.

This report is oriented toward 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 document, are published elsewhere (10). Also, integrated approaches to the care of HIV-infected persons are addressed separately (12).

It is recognized that new data on prevention of OIs in HIV-infected persons are emerging, and that randomized controlled trials addressing some unresolved issues in OI prophylaxis are ongoing. The OI Working Group has therefore developed a mechanism for routine periodic review of emerging data, and for updating these guidelines on a regular basis. The most recent information is available from the AIDS Treatment Information Service world-wide web site (www.hivatis.org).

Copies of this report can be obtained from ATIS, telephone 1-800-448-0440 or 301-217-0023 (international) or 1-800-243-7012 (TTY). In addition, pamphlets containing material appropriate for patients can be obtained from ATIS, and also on the CDC's Division of HIV/AIDS Prevention internet homepage (www.cdc.gov/hiv).

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