An updated version of the Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents has been posted on the HIV/AIDS Treatment Information Service (ATIS) website (1, 2). The new Guidelines are based on the latest research findings and provide recommendations on how to make optimal use of the many antiretroviral medications and sophisticated laboratory tests now available.
The increased number and availability of treatment options for HIV-infected individuals and the rapid evolution of new information has introduced extraordinary complexity into the treatment of HIV. In 1996, the Department of Health and Human Services and the Henry J. Kaiser Family Foundation convened a Panel on Clinical Practices for the Treatment of HIV to develop guidelines for the clinical management of HIV-infected adults and adolescents.
The latest Guidelines include recommendations for the use in clinical practice of recently developed tests to help determine if the virus a patient is carrying has developed resistance to one or more antiretroviral drugs. The likelihood of reducing viral load to undetectable levels is significantly increased when results of resistance testing are available.
The Guidelines also discuss other primary goals of antiretroviral therapy including:
• restoring or preserving the patient's immunologic function;
• improvement in quality of life;
• reduction of HIV-related illness and death.
The Guideline proposes that care should ideally be supervised by an expert, and makes recommendations for laboratory monitoring including plasma HIV RNA, CD4+ T cell counts and HIV drug resistance testing. Guidelines are also provided for antiretroviral therapy, including when to start treatment, what drugs to initiate, when to change therapy and therapeutic options when doing this. 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 compliance, and carry serious potential consequences as a result of 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 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 (RT-PCR 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 to 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 to predict prognosis.
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-log (10-fold) decrease at eight weeks and no detectable virus (<50 copies/mL) at 4-6 months after initiation of treatment. Failure of therapy (i.e., plasma HIV RNA levels exceeding 50 copies/mL) 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 for 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 set tings 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 will be posted on the HIV/AIDS Treatment Information Service (ATIS) website (2).
1. NIH News Release, 28 January 2000.
2. Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents. HIV/AIDS Treatment Information Service (ATIS), http://www.hivatis.org