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When and What Antiretroviral Therapy to Start
M S Hirsch
Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA
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Background: Two of the most perplexing questions related to antiretroviral therapy for HIV infection are when to start and what treatment regimen to begin. It is unlikely that the question of when to start will be answered by controlled trials, and decisions will, thus, be based largely on retrospective and cohort studies. In contrast, many clinical trials are beginning to define which regimens are the most appropriate for treatment initiation.
Methods: Published and unpublished reports of cohort studies and clinical trials were reviewed and synthesized in order to make recommendations for 2003.
Results: There are major outcome differences between those who start therapy when CD4 cell counts are below or above 200/mm3. Some studies suggest differences in outcome between those who start below or above 350/mm3, whereas others do not. In addition, some studies suggest that HIV-1 RNA plasma levels may help guide decisions, whereas others do not. ACTG 384 compared different strategies for sequencing antiretroviral regimens in 980 treatment-naive subjects using a composite endpoint including virologic failure, toxicity and treatment discontinuation criteria.
Results: demonstrated that the potency of antiretroviral combinations depends on how they are combined, and that ZDV+3TC+EFV is a particularly effective initial regimen. Gilead 903 compared 2 active regimens (either d4T or TDF in combination with 3TC + EFV), and showed equivalent antiviral activity between the regimens, but decreased toxicity in the TDF arm. Abbott M98-863 demonstrated that a combination including LPV/r+d4T+3TC had superior antiviral activity to one including NFV+ d4T + 3TC. Other promising drugs for initial therapy, e.g., atazanavir, are also under study.
Conclusions: Initiation of antiretroviral therapy is indicated at CD4 cell counts somewhere between 200–350/mm3 with currently available agents. Treatment decisions need to be individualized within that CD4 cell range. Particularly useful initial combination regimens include ZDV+3TC+EFV, TDF+3TC+EFV, and d4T+3TC+LPV/r.
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