Background:  Emerging resistance poses a threat to the ongoing durability of HAART regimens. However, there is still limited evidence that reduced sensitivity to antiretrovirals leads to rapid disease progression or death in the HAART era. The objective of this study was to determine the effect of reduced sensitivity to antiretrovirals on survival.

Methods:  The study was a population-based analysis of a cohort of antiretroviral therapy naïve HIV-positive men and women 18 years or older in British Columbia, Canada. Participants were antiretroviral therapy-naïve, initiated triple combination therapy between August 1, 1996 and July 31, 2000. The primary endpoint was all-cause mortality. Cox-proportional hazard regression was used to model the simultaneous effect of prognostic variables on survival and proportional hazards marginal structural modeling was also used to address potential confounding between time-dependent variables. Event-free subjects were right censored as of June 30, 2003.

Results:  A total of 1388 participants aged 18 years and older initiated triple combination therapy between August 1996 and July 2000. A total of 238 deaths were identified over the follow-up period with an all-cause mortality rate of 17.2%. HIV-drug resistance to any class was observed in 393 (28.3%) participants. After controlling for other prognostic explanatory variables that were significant in the final model, persons who exhibited reduced sensitivity to any antiretroviral had death rates that were 1.80 times (95% CI 1.34 to 2.41) higher than those who did not exhibit this type of resistance. In the marginal structural model persons who exhibited reduced sensitivity to non-nucleoside reverse transcriptase inhibitors and other nucleosides had death rates that were 2.07 (95% CI 1.19 to 3.60) and 2.93 (95% CI 1.44 to 5.96) times higher respectively than those who did not exhibit these types of resistance. Reduced sensitivity to protease inhibitors was shown to be protective (HR = 0.32; 95% CI 0.11 to 0.97).

Conclusions:  Our results demonstrate that participants who developed specific resistant strains of HIV over the study period did not survive as long as those without these resistant strains. 

Keywords: resistance; antiretroviral naive; survival