Predictors of successful genotype-guided antiretroviral therapy in treatment-experienced individuals over calendar years: a cohort study.

Background: The continuous development of new drugs for use in triple-drug combination antiretroviral therapy (cART) has dramatically decreased morbidity and mortality in HIV-1 infected individuals. However, increasing drug resistance could be associated with a poor outcome.

Objectives: To determine the efficacy of resistance genotype-guided antiretroviral regimens in combination antiretroviral therapy (cART)-failing patients over calendar years and its predictors.

Study Design: Patients, with an available resistance genotype performed between 1999 and 2008, who failed a highly active antiretroviral therapy (HAART) regimen, changed therapy within 6 months from genotype and maintained the same salvage regimen, were selected from a clinical cohort database. Virologic efficacy was analyzed using time-to virologic suppression (VS, HIV-1 RNA<50 copies/ml).

Results: In 270 sequences analyzed from 212 patients, after a median follow-up of 23 weeks, there were 160 patients with VS (59.3%). Mean regimens' genotypic sensitivity score (GSS) increased from 1.86 (SD+/-0.92) in 1999-2001, to 2.29 (SD+/-0.96) in 2005-2008 (p=0.001 for trend). VS was achieved in 39% of those patients genotyped in 1999-2001, and increased to 69% for patients with genotyping performed between 2005 and 2008 (p<0.001). More recent calendar year, younger age and less use of suboptimal therapy were predictors of more effective HAART regimens but only more recent calendar year maintained a trend toward significance in a multivariable model. More recent genotyping calendar year, younger age, lower number of HAART regimens experienced, lower HIV-1 RNA and higher GSS independently conveyed and increased the probability of VS.

Conclusions: Resistance-guided salvage antiretroviral therapy was more effective during more recent calendar years, independent from other measurable confounders, including the GSS of the employed regimen. Convenience and tolerability of newer agents should account for the observed effect.