High viral load, previous fosamprenavir use and more recent HIV diagnosis correlate with darunavir failure in salvage therapy in Sao Paulo, Brazil

Abstract

Purpose of the studyEfficacy of DRV‐containing regimen in antiretroviral‐experienced patients in Brazil is unknown. The aim of this study was to evaluate the prevalence and risk factors associated with virologic failure (VF) to DRV containing salvage regimen in experienced HIV‐infected patients in Sao Paulo and also determine the prevalence of DRV resistance associated mutations (RAM) in this population.MethodsRetrospective study of 131 patients who started a DRV‐containing salvage regimen between 12/2007 to 12/2009 in 2 centers in Sao Paulo. Protease resistance mutations listed by 2011 IAS‐USA panel update were considered. Genotypic sensitivity score (GSS) was calculated for the proposed regimen using the 2008 Rega algorithm. We have assessed VF during 48 weeks of follow up and VF was defined as the failure to achieve viral suppression in 48 weeks or viral rebound after suppression. Stopping the use of DRV for any reason was also considered VF.Summary of resultsWe analysed 131 patients, 71% male, median age 44y. More than half of the patients had a baseline CD4 cell count<200/mm3 (58,9%) although only 21,4% presented a VL ≥100.000 copies/ml. 78,6% had previous used more than 2 PI and more than half of the patients harbored viruses with at least 11 IAS PI resistance mutations (59,5%) The majority of patients had less than 2 DRV RAM (84,7%) and the most prevalent major and minor DRV RAM were respectively I84V (24,4%) and L33F (34,3%). Most patients (79,4%) have received more than 2 active drugs in their regimen. Twenty patients (15,3%) have failure in achieving VL <50copies/ml at 48 weeks. Ten patients were lost of follow up and the remaining 10 were treatment failure. In multivariate analysis, VL≥ 100.000 copies/mL (p=0,002), less than 15 years of HIV diagnosis (p=0,013) and previous fosamprenavir use (p=0,027) were independently predictive of VF.ConclusionsThis study, conducted in routine clinical conditions, is probably the large cohort to evaluate risk factors to VF with DRV containing regimen worldwide and is the first one to evaluate prevalence of VF with DRV containing regimen in Brazil. We found an elevated response rate in this population (84,7%) which couples with the low number of DRV RAM despite the elevated number of previous PI used and by the high GSS. The factors associated with VF were similar to previous reports except for the time of HIV diagnosis, and one can speculate that this correlates with lower adherence in this group.