Why are baseline HIV RNA levels 100,000 copies/mL or greater associated with mortality after the initiation of antiretroviral therapy?

Abstract

Background: There is conflicting evidence regarding the impact of baseline plasma HIV RNA on virologic responses after the initiation of triple-drug antiretroviral therapy (highly active antiretroviral therapy [HAART]). This has made it difficult to interpret the recently reported association between baseline plasma HIV RNA and mortality. We evaluated whether baseline CD4 cell count and plasma HIV RNA predicted virologic suppression (<500 copies/mL) and rebound (> or =500 copies/mL) among adherent HIV-infected patients.

Methods: Antiretroviral-naive HIV-infected patients were stratified by baseline CD4 cell count, plasma HIV RNA, and adherence level. Cox and logistic regression were used to evaluate the time to suppression and rebound and the odds of ever achieving HIV RNA suppression.

Results: A total of 1422 individuals initiated HAART between August 1, 1996 and July 31, 2000 and were followed to March 31, 2002. Adherent patients with HIV RNA levels > or =100,000 copies/mL and 50 to 99,999 copies/mL were slower to suppress HIV RNA than patients with baseline HIV RNA <50,000 copies/mL in Kaplan-Meier analyses. Although the odds of RNA suppression among adherent patients with baseline RNA levels <50,000 copies/mL and 50 to 99,999 copies/mL were similar (P = 0.197), patients with baseline HIV RNA > or =100,000 copies/mL were markedly less likely ever to achieve suppression during follow-up (adjusted odds ratio: 0.27 [95% confidence interval: 0.13-0.54]; P < 0.001). No differences in the rate of virologic rebound were observed between adherent patients in the various baseline HIV RNA strata, and CD4 cell count was not associated with suppression or rebound.

Conclusions: Baseline HIV RNA > or =100,000 copies/mL was associated with a significantly lower likelihood of ever achieving HIV RNA suppression during follow-up. These findings likely explain the association between baseline HIV RNA levels and mortality and have important implications for the development of therapeutic guidelines.