Does short-term virologic failure translate to clinical events in antiretroviral-naïve patients initiating antiretroviral therapy in clinical practice?

AIDS. 2008 Nov 30;22(18):2481-92. doi: 10.1097/QAD.0b013e328318f130.

Abstract

Objective: To determine whether differences in short-term virologic failure among commonly used antiretroviral therapy (ART) regimens translate to differences in clinical events in antiretroviral-naïve patients initiating ART.

Design: Observational cohort study of patients initiating ART between January 2000 and December 2005.

Setting: The Antiretroviral Therapy Cohort Collaboration (ART-CC) is a collaboration of 15 HIV cohort studies from Canada, Europe, and the United States.

Study participants: A total of 13 546 antiretroviral-naïve HIV-positive patients initiating ART with efavirenz, nevirapine, lopinavir/ritonavir, nelfinavir, or abacavir as third drugs in combination with a zidovudine and lamivudine nucleoside reverse transcriptase inhibitor backbone.

Main outcome measures: Short-term (24-week) virologic failure (>500 copies/ml) and clinical events within 2 years of ART initiation (incident AIDS-defining event, death, and a composite measure of these two outcomes).

Results: Compared with efavirenz as initial third drug, short-term virologic failure was more common with all other third drugs evaluated; nevirapine (adjusted odds ratio = 1.87, 95% confidence interval (CI) = 1.58-2.22), lopinavir/ritonavir (1.32, 95% CI = 1.12-1.57), nelfinavir (3.20, 95% CI = 2.74-3.74), and abacavir (2.13, 95% CI = 1.82-2.50). However, the rate of clinical events within 2 years of ART initiation appeared higher only with nevirapine (adjusted hazard ratio for composite outcome measure 1.27, 95% CI = 1.04-1.56) and abacavir (1.22, 95% CI = 1.00-1.48).

Conclusion: Among antiretroviral-naïve patients initiating therapy, between-ART regimen, differences in short-term virologic failure do not necessarily translate to differences in clinical outcomes. Our results should be interpreted with caution because of the possibility of residual confounding by indication.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Anti-Retroviral Agents / therapeutic use*
  • Disease-Free Survival
  • Drug Interactions
  • Drug Resistance, Viral
  • Drug Therapy, Combination
  • Epidemiologic Methods
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • HIV Infections / virology
  • HIV-1*
  • Humans
  • Male
  • Middle Aged
  • Odds Ratio
  • RNA, Viral / metabolism*
  • Reverse Transcriptase Inhibitors / therapeutic use*
  • Treatment Outcome
  • Viral Load
  • Young Adult

Substances

  • Anti-Retroviral Agents
  • RNA, Viral
  • Reverse Transcriptase Inhibitors