Background:  Antiretroviral therapy is not curative and any ongoing viral replication can increase the risk of selecting for virus populations that are resistant to treatment.  The objective of this study is to determine the effect of reduced sensitivity to antiretrovirals in the first year on survival in subsequent years.

Methods: This analysis is based upon HIV-positive individuals aged 18 years and older who initiated triple combination therapy between August 1996 and July 2000 and who have been followed for at least 1 year.  The first 12 months was used to measure intermittent use of therapy and the emergence of resistance to antiretrovirals (3TC, other NRTI, NNRTI, and PI). Age, CD4 cell count, plasma HIV-1 RNA levels, prior AIDS diagnosis, history of injection drug use, and physician's experience were measured at the end of year 1. Cox-proportional hazard regression analysis was used to model the simultaneous effect of prognostic variables on survival from the first year onwards. 

Results:  A total of 851 participants aged 18 years and over initiated triple combination therapy between August 1996 and July 2000 and had at least 1 year of follow-up.  As of March 31, 2002, a total of 93 deaths were identified in the study population with an all cause mortality rate of 10.9%. HIV-drug resistance to any class was observed in 148 (17%) persons in the first year.  Of these participants, 3 (<1%) exhibited resistance to all 3 classes, 41 (5%) to 2 classes, and 104 (12%) to 1 class.  A total of 94 (11%) exhibited resistant to 3TC, 45 (5%) to other nucleosides, 49 (6%) to NNRTI, and 28 (3%) to PI. After adjusting for all prognostic factors found to be significant in the univariate analysis, persons who exhibited reduced sensitivity to NNRTI in the first year were 2.96  times (95% CI: 1.52, 5.75; p = 0.001) more likely to die than those who did not.  In a separate analysis restricted to persons taking NNRTI-based regimens only, persons with reduced sensitivity to NNRTI and 3TC in the first year were 4.57 times (95%CI: 1.02, 20.61) more likely to die than those who did not.

Conclusions:  These preliminary results indicate that although the emergence of resistance remains relatively low after the first year on therapy, persons who exhibited reduced sensitivity to one or more antiretrovirals during this period are at greater risk of death

Keywords: Resistance; Mortality; Cohort study