The Relation between Baseline HIV Drug Resistance and Response to Antiretroviral Therapy: Re-Analysis of Retrospective and Prospective Studies Using a Standardized Data Analysis Plan

TLDR

The study re‑analysed 12 HIV‑1 treatment studies to evaluate how baseline drug resistance predicts virological response to antiretroviral therapy. The authors pooled nine clinical trials and three observational cohorts, using a standardized plan to assess virological failure at week 24 and to evaluate baseline plasma RNA, regimen drug count, and genotypic or phenotypic susceptibility as predictors. Both genotypic and phenotypic resistance independently predicted virological failure, with each additional drug to which the virus was sensitive reducing the odds of failure by roughly twofold (genotype) or two‑to‑threefold (phenotype).

Abstract

To assess the relation between resistance to antiretroviral drugs for treatment of HIV-1 infection and virological response to therapy, results from 12 different studies were re-analysed according to a standard data analysis plan. These studies included nine clinical trials and three observational cohorts. The primary end-point in our analyses was virological failure by week 24. Baseline factors that were investigated as predictors of virological failure were plasma HIV-1 RNA, the number and type of new antiretroviral drugs in the regimen, and viral susceptibility to the drugs in the regimen, determined by genotyping or phenotyping methods. These analyses confirmed the importance of both genotypic and phenotypic drug resistance as predictors of virological failure, whether these factors were analysed separately or adjusted for other baseline confounding factors. In most of the re-analysed studies, the odds of virological failure were reduced by about twofold for each additional drug in the regimen to which the patient's virus was sensitive by genotyping methods, and by about two- to threefold for each additional drug that was sensitive by phenotyping.