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

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.

Figure 1. Temporal trends in antiretroviral prescribing patterns among 13,546 antiretroviral naïve HIV-infected patients in the Antiretroviral Therapy Cohort Collaboration (ART-CC) initiating ART with ZDV/3TC and stratified by 3^rd drug, 2000 – 2005

EFV, efavirenz; NVP, nevirapine; LPV/r, lopinavir/ritonavir; NFV, nelfinavir; ABC, abacavir Shaded bars represent the proportion of ART-CC patients initiating HAART with each of the listed 3^rd drugs during each of the calendar years from 2000 – 2005.

Figure 2. Estimated AIDS free survival among 13,546 antiretroviral naïve HIV-infected patients in the Antiretroviral Therapy Cohort Collaboration (ART-CC) initiating ART with ZDV/3TC stratified by 3^rd drug, 2000 – 2005

Survival curves shown are estimated from a Weibull model with follow-up censored at 2 years, with covariates set at the average value across the population of patients and for the cohort with median survival. Corresponding adjusted hazard ratios are shown in Table 3.