Response to Antiretroviral Treatment After Failure of NNRTI Plus NRTIs-Based Therapy. Data from the ARCA Collaborative Group

Elena      Seminari; Annalisa      De Silvestri; Genny      Meini; Annapaola      Callegaro; Enzo      Boeri; Grazia      Punzi; Nicola      Gianotti; Bianca      Bruzzone; Carmine      Tinelli; Paolo      Grossi

Abstract

Objective: The aim of the present study was to evaluate the virological response to a new antiretroviral treatment (ART2) after failure of a nonnucleoside reverse transcriptase inhibitor (NNRTI) plus two nucleoside reverse transcriptase inhibitors (NRTIs)-containing regimen.

Design: Retrospective observational study based on the Italian ARCA cohort database. Adult patients were included if they had a virological failure (defined as plasma viral load above 500 copies/ml in two subsequent visits) while on a treatment with one NNRTI plus 2 NRTIs, had an available HIV genotype.

Results: Patients on ART2 were followed up for 791 person/year and median follow up was 10.8 months(IQR 5.2-26). Variables associated with reduced risk of ART2 virological failure at univariable analysis had started the treatment in recent years (HR 0.90; 95% CI 0.86-0.94, p<0.0001) and duration of previous NNRTI treatment (HR 0.995; 95%CI 0.990-0.990, p=0.045). Variables associated with increased risk of virological failure of ART2 were a higher plasma viral load (pVL) at baseline(HR 1.2; 95% CI 1.07-1.34, p=0.002) and the type of treatment, in particular an unboosted PIcontaining regimen vs. a boosted PI-containing regimen(HR 1.6; 95%CI 1.25-2.04 p<0.0001) and a non–PI-containing vs. a boosted PI-containing regimen (HR 1.56; 95% CI 1.25-1.96, p<0.0001). At multivariable analysis, year of ART2 start, pVL at NNRTI failure as well as using a boosted PI remained statistically significant predictors.

Conclusion: This study highlights the role of drugs with high genetic barrier, such as boosted PI as a cornerstone to build a new antiretroviral treatment in patients failing a NNRTI based regimen.

Keywords: Drug resistance, genotypic susceptibility score, HIV infection, NNRTI failure, rescue therapy, viral rebound, antiretroviral, virological failure, CD4+, regimen