Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents, February 5, 2001

Abstract

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 makes recommendations for laboratory monitoring including plasma HIV RNA, CD4 cell counts and HIV drug resistance testing. The report 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 considerations are provided for adolescents and pregnant women. As with treatment of other chronic conditions, therapeutic decisions require a mutual understanding between the patient and the health care provider regarding the benefits and risks of treatment. Antiretroviral regimens are complex, have major side effects, pose difficulty with adherence, and carry serious potential consequences from the development of viral resistance due to non-adherence 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 six months of HIV seroconversion, and all patients with symptoms ascribed to HIV infection. Recommendations for offering antiretroviral therapy in asymptomatic patients require analysis of many real and potential risks and benefits. In general, treatment should be offered to individuals with fewer than 350 CD4+ T cells/mm3 or plasma HIV RNA levels exceeding 30,000 copies/mL (bDNA assay) or 55,000 copies/mL (RT-PCR assay). The strength of the recommendation to treat asymptomatic patients should be based on the willingness and readiness of the individual to begin therapy; the degree of existing immunodeficiency as determined by the CD4+ T cell count; the risk of disease progression as determined by the CD4+ T cell count and level of plasma HIV RNA; the potential benefits and risks of initiating therapy in asymptomatic individuals; and the likelihood, after counseling and education, of adherence to the prescribed treatment regimen. Once the decision has been made to initiate antiretroviral therapy, the goals should be maximal and durable suppression of viral load, restoration and/or preservation of immunologic function, improvement of quality of life, and reduction of HIV-related morbidity and mortality. Results of therapy are evaluated primarily with plasma HIV RNA levels; these are expected to show a one-log10 decrease at eight weeks and no detectable virus (<50 copies/mL) at 4-6 months after initiation of treatment. Failure of therapy at 4- 6 months may be ascribed to non-adherence, inadequate potency of drugs or suboptimal levels of antiretroviral agents, viral resistance, and other factors that are poorly understood. Patients whose therapy fails in spite of a high level of adherence to the regimen should have their regimen changed; this change should be guided by a thorough drug treatment history and the results of drug resistance testing. Optimal changes in therapy may be especially difficult to achieve for patients in whom the preferred regimen has failed, due to 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 to participate in a clinical trial with or without access to new drugs or to use a regimen that may not achieve complete suppression of viral replication.

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 HIV/AIDS Treatment Information Service website (http://www.hivatis.org).