Does short-term virologic failure translate to clinical events in antiretroviral-naïve patients initiating antiretroviral therapy in clinical practice?
Antiretroviral Therapy Cohort Collaboration (ART-CC), Michael J Mugavero, Margaret May, Ross Harris, Michael S Saag, Dominique Costagliola, Matthias Egger, Andrew Phillips, Huldrych F Günthard, Francois Dabis, Robert Hogg, Frank de Wolf, Gerd Fatkenheuer, M John Gill, Amy Justice, Antonella D'Arminio Monforte, Fiona Lampe, Jose M Miró, Schlomo Staszewski, Jonathan A C Sterne
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.
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Source: PubMed