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When to Start Antiretrovirals: Later May Be Fine

Two studies suggest that delaying antiretroviral therapy until CD4 counts near 200 cells/mm³ may be a safe strategy for many patients.

The recently revised DHHS guidelines recommend that HIV-infected patients begin treatment when CD4 counts drop below 350 cells/mm³ or viral loads exceed 30,000 copies/ml, but many experts feel these rules are likely to be revised again in coming years. Two studies now suggest that treatment may often be safely withheld until later stages of disease.

Researchers analyzed the viral-load response to 3-drug treatment in more than 3000 treatment-naive patients from 3 European cohorts. Patients with pretreatment CD4 counts less than 200 cells/mm³ reached undetectable viral-load levels (<500 copies/ml and, for a subset, <50 copies/ml) more slowly and less reliably than those with pretreatment counts above 200 cells/mm³. However, there was no difference in patterns of viral-load response among those with pretreatment CD4 counts between 200 and 349 cells/mm³, and those with counts greater than 350 cells/mm³. Patients with pretreatment viral loads more than 100,000 copies/ml had a slower rate of viral-load reduction than did other patients, but those with pretreatment viral loads less than10,000 copies/ml, and those with viral loads between 10,000 and 99,999 copies/ml responded similarly. Rates of viral-load rebound were similar across all pretreatment CD4 strata.

In another study, Canadian researchers looked at mortality in a cohort of 1219 treatment-naive patients initiating 3-drug therapy. Likelihood of survival after 36 months was predicted by pretreatment CD4-cell count: it was significantly lower among those with pretreatment CD4 counts less than 200 cells/mm³ than among those with higher counts, and even lower in patients with pretreatment CD4 counts less than 50 cells/mm³. However, survival was not significantly different for patients with pretreatment CD4 counts of 200 to 350, 350 to 500, and more than 500 cells/mm³. In a multivariate analysis, pretreatment viral load did not influence survival in this study.

The results of both these studies are subject to the caveat that formal criteria for beginning antiretrovirals were not specifically delineated in either. Thus, patients starting therapy at different CD4 thresholds could differ in other important ways that could bias outcome. While acknowledging this problem, however, an editorialist concludes that these results "appear to support" delaying treatment in many chronically infected patients until the CD4 count approaches 200 cells/mm³.

— Abigail Zuger, MD

Dr. Zuger is an Associate Editor of ACC.

Published in Journal Watch HIV/AIDS Clinical Care January 1, 2002

Citation(s):

Philips 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.

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

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.

Pomerantz RJ. Initiating antiretroviral therapy during HIV infection: Confusion and clarity. JAMA 2001 Nov 28; 286:2597-9.

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