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When to Start Antiretroviral Therapy -- Additional Insights

Initiation of antiretroviral therapy is often delayed in patients with asymptomatic disease, because immediate risks for drug toxicity may be worse than the morbidity of HIV disease. But how long can therapy be delayed before the response is jeopardized? Insights into this practical and important question are provided in 2 recently published studies.

Phillips and colleagues examined whether baseline plasma HIV RNA level or CD4-cell count influenced the virologic response to a potent antiretroviral regimen. Virologic response (proportion of patients who achieved HIV RNA <500 copies/mL), time to virologic response, and time to viral rebound (HIV RNA >500 copies/mL) were outcome variables. The analysis incorporated data from 3226 antiretroviral-naive participants in 3 ongoing longitudinal cohort studies in Europe. Median duration of follow-up was approximately 2 years; only patients initiating 3-drug regimens after 1996 were included. The major findings were that CD4-cell count predicted neither virologic response nor rebound. Pretreatment levels of HIV RNA >100,000 copies/mL were associated with slowed response to antiretroviral therapy but not with durability of the response.

Hogg and colleagues focused on survival and clinical, not virologic, outcomes in 1219 antiretroviral-naive Canadian patients, at various stages of HIV infection, who initiated triple-drug therapy after 1996. Twenty-seven different regimens were used as initial therapy. Median follow-up in this study was also approximately 2 years. The key finding was that the death rate and the development of AIDS-defining conditions were highest in patients who started therapy at a CD4 cell count <200 cells/mm³. The risk for death was 7-fold higher in patients with CD4 counts <50 cells/mm³ and 3-fold higher in those with CD4 counts 50 to 199 cells/mm³ than in those with CD4 counts of at least 200 cells/mm³. HIV RNA level was not an independent predictor of survival.

Comment: Together, these data indicate that delaying therapy until the CD4 count has declined below 200 cells/mm³ is associated with reduced survival and poor clinical outcome. Starting therapy at higher CD4 cell counts (200 cells/mm³) did not produce demonstrably different benefit in any strata in terms of survival or virologic outcome, at least in the short term. However, therapy in patients with CD4 counts 200 provides many more subtle clinical benefits and risks not measured in these analyses; thus, providers are left to individualize each decision to start therapy in patients with high CD4 cell counts until more detailed studies, with longer follow-up, are completed. (

— Diane V. Havlir, MD

Published in Journal Watch Infectious Diseases December 21, 2001

Citation(s):

Phillips AN et al. HIV viral load response to antiretroviral therapy according to the baseline CD4 cell count and viral load. JAMA 2001 Nov 28; 286:2560-7.

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Hogg RS et al. Rates of disease progression by baseline CD4 cell count and viral load after initiating triple-drug therapy. JAMA 2001 Nov 28; 286:2568-77.

• Original article (Subscription may be required)
• Medline abstract (Free)