Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents

The availability of an increasing number of antiretroviral agents and the rapid evolution of new information has introduced extraordinary complexity into the treatment of HIV-infected persons. In 1996, the Department of Health and Human Services and the Henry J. Kaiser Family Foundation convened the Panel on Clinical Practices for the Treatment of HIV to develop guidelines for the clinical management of HIV-infected adults and adolescents. This report recommends that care should be supervised by an expert, and it makes recommendations for laboratory monitoring with particular emphasis on measurement of plasma levels of HIV RNA.It also provides guidelines for antiretroviral therapy, including when to start treatment, what drugs to initiate, when to change therapy, and therapeutic options when changing therapy. Special consideration is given to adolescents and pregnant women. As with decisions about treatment of other chronic conditions, therapeutic decisions about HIV disease require a mutual understanding between the patient and the health care provider regarding the benefits and risks of treatment. Like treatment for most chronic diseases, antiretroviral regimens are complex, have major side effects, pose difficulty with compliance, and carry serious potential consequences with the risk for resistance from nonadherence to the drug regimen or suboptimal levels of antiretroviral agents. Patient education and involvement in therapeutic decisions is important for all medical conditions but is considered especially critical for HIV infection and its treatment. With regard to specific recommendations, treatment should be offered to all patients with the acute HIV syndrome, those within 6 months of seroconversion, and all patients with symptoms ascribed to HIV infection.Recommendations for offering antiretroviral therapy to asymptomatic patients depend on virologic and immunologic factors. In general, treatment should be offered to individuals with fewer than 500 CD4+ T cells/mm3 or plasma HIV RNA levels exceeding 10 000 copies/mL (branched DNA assay) or 20 000 copies/mL (reverse transcriptase polymerase chain reaction assay). The strength of the recommendation to treat asymptomatic patients should be based on the patient's willingness to accept therapy, the probability of adherence with the prescribed regimen, and the prognosis in terms of time to an AIDS-defining complication as predicted by plasma HIV RNA levels and CD4+ T-cell counts, which independently help predict prognosis. Once the decision has been made to initiate antiretroviral therapy, the goal is maximum viral suppression for as long as possible. Results of clinical trials to date indicate that this may currently be best achieved with a potent protease inhibitor in combination with two nucleoside analogue reverse transcriptase inhibitors (NRTIs). Another option is the combination of saquinavir plus ritonavir combined with one or two NRTIs. Other currently available regimens may be used in selected settings but are considered by many to be less likely to produce maximum viral suppression. Results of therapy are evaluated primarily with plasma HIV RNA levels; these are expected to show a one-log (10-fold) decrease at 8 weeks and no detectable virus (<500 copies/mL) at 4 to 6 months after initiation of treatment. Failure of therapy (i.e., plasma HIV RNA levels >500 copies/mL) at 4 to 6 months may be ascribed to nonadherence, inadequate potency of drugs or suboptimal levels of antiretroviral agents, resistance, and other factors that are poorly understood. Patients whose therapy fails should change to at least two new agents that are not likely to show cross-resistance with drugs given previously; ideally, the regimen should be changed to a completely new regimen that is devoid of anticipated cross-resistance and for which clinical trial data support a high probability of viral response. Rational changes in therapy may be especially difficult to achieve for patients for whom the preferred regimen has failed, because of limitations in the available alternative antiretroviral regimens that have documented efficacy; these decisions are further confounded by problems with adherence, toxicity, and resistance. In some settings, it may be preferable for a patient to participate in a clinical trial with or without access to new drugs or to use a regimen that may not achieve the optimal virologic goal. It is emphasized that concepts relevant to HIV management evolve rapidly.The Panel has a mechanism to update recommendations on a regular basis, and the most recent information is available on the AIDS Treatment Information Service World Wide Web site (http://www.hivatis.org). These Guidelines were developed by the Panel on Clinical Practices for Treatment of HIV Infection convened by the Department of Health and Human Services and the Henry J.Kaiser Family Foundation. Leadership of the Panel consists of Anthony S. Fauci, National Institutes of Health, Bethesda, MD (co-chair); John G. Bartlett, Johns Hopkins University, Baltimore, MD (co-chair); Eric P. Goosby, Department of Health and Human Services (convener); Mark D. Smith, California HealthCare Foundation, San Francisco, CA, formerly of the Henry J. Kaiser Foundation (convener), succeeded by Sophia W. Chang, Henry J. Kaiser Foundation. Members of the Panel who participated in the development of this document included Jean Anderson (Johns Hopkins University, Baltimore, MD), Rodney Armstead (Watts Health Foundation, Inc., Inglewood, CA), A. Cornelius Baker (National Association of People with AIDS, Washington, DC), David Barr (Forum for Collaborative HIV Research, Washington, DC), Samuel Bozzette (San Diego Veterans Affairs Medical Center, San Diego, CA), Spencer Cox (Treatment Action Group, New York, NY), Martin Delaney (Project Inform, San Francisco, CA), Fred Gordin (Veterans Administration Medical Center, Washington, DC), Wayne Greaves (Howard University, Washington, DC), Mark Harrington (Treatment Action Group, New York, NY), John J. Henning (American Medical Association, Chicago, IL), Martin S. Hirsch (Massachusetts General Hospital, Boston, MA), Jeffrey Jacobs (AIDS Action Council), Richard Marlink (Harvard AIDS Institute, Cambridge, MA), Celia Maxwell (AIDS Education and Training Center, Washington, DC), John W. Mellors (University of Pittsburgh, Pittsburgh, PA), David B. Nash (Thomas Jefferson University, Philadelphia, PA), Sallie Perryman (New York State Department of Health, New York, NY), Robert T. Schooley (University of Colorado, Denver, CO), Renslow Sherer (Cook County HIV Primary Care Center, Chicago, IL), Stephen A. Spector (University of California San Diego, La Jolla, CA), Gabriel Torres (St. Vincent's Hospital, New York, NY), Paul Volberding (University of California, San Francisco, CA); participants from the Department of Health and Human Services: Barbara A. Brady (Office of HIV/AIDS Policy), Oren Cohen (National Institutes of Health), Elaine M. Daniels (Office of HIV/AIDS Policy), David Feigal (Food and Drug Administration), Mark Feinberg (National Institutes of Health), Helene D. Gayle (Centers for Disease Control and Prevention), T. Randolph Graydon (Health Care Financing Administration), Jonathan Kaplan (Centers for Disease Control and Prevention), Abe Macher (Health Resources and Services Administration), R. Frank Martin (Indian Health Service), Henry Masur (National Institutes of Health), Lynne Mofenson (National Institutes of Health), Jeffrey Murray (Food and Drug Administration), Joseph O'Neill (Health Resources and Services Administration), Lucille C. Perez (Substance Abuse and Mental Health Services Administration), Richard Riseberg (Office of the Secretary), Samuel Shekar (Health Care Financing Administration), Sharilyn K. Stanley (National Institutes of Health), Jack Whitescarver (Office of AIDS Research). The Panel would like to extend special appreciation to Charles Carpenter (Brown University School of Medicine, Providence, RI) for his advice in the development of this document and Gerry Bally (Health Canada) and Anita Rachlis (Sunnybrook Health Science Centre, University of Toronto, Toronto, Canada) for their participation. The Panel would also like to acknowledge the special contributions of Sharilyn K. Stanley, Barbara A. Brady, and Elaine M. Daniels in the preparation of this document.