학술논문

No impact of HIV-1 protease minority resistant variants on the virological response to a first-line PI-based regimen containing darunavir or atazanavir.
Document Type
Journal Article
Source
Journal of Antimicrobial Chemotherapy (JAC). Jan2018, Vol. 73 Issue 1, p173-176. 4p. 2 Charts.
Subject
*THERAPEUTICS
*HIV infections
*PROTEOLYTIC enzymes
*DARUNAVIR
*ATAZANAVIR
*DRUG resistance
*VIRAL mutation
*MEDICAL virology
*ANTI-HIV agents
*RITONAVIR
*HIV protease inhibitors
*COMBINATION drug therapy
*DRUG resistance in microorganisms
*HIV
*PROTEINS
*VIRAL load
Language
ISSN
0305-7453
Abstract
Objectives: To evaluate, in a clinical cohort of HIV-1-infected patients, the prevalence of PI minority resistant variants (MRV) at ART baseline and their impact on the virological response to a first-line PI-based regimen.Patients and Methods: In an observational single-centre cohort, we assessed all ART-naive patients initiating a first-line regimen including two NRTI and one boosted PI, darunavir/ritonavir or atazanavir/ritonavir, between January 2012 and March 2015. Ultra-deep sequencing of the pol gene was performed using Illumina® technology. Protease mutations were identified using the WHO transmitted drug resistance list and major PI resistance mutations (IAS-USA drug resistance mutations list).Results: Ninety-four and 16 patients initiating a darunavir/ritonavir-based regimen and an atazanavir/ritonavir-based regimen, respectively, were assessed. Twenty-eight percent of the patients were HIV-1 subtype B, 39% CRF02_AG and 33% other non-B subtypes. Thirteen patients (13.8%) in the darunavir group and three patients (18.8%) in the atazanavir group experienced a virological failure (VF). Overall, 13 (11.8%) subjects had PI MRV at baseline in the median proportion of 1.3% (IQR = 1.1-1.7). The most prevalent PI MRV were G73C (n = 5) and M46I (n = 3). The proportion of patients harbouring baseline PI MRV was similar between those with virological success (10.6%) and those experiencing VF (18.8%) (P = 0.40). No difference was observed in the rate of PI MRV by viral subtype (P = 0.51) or by PI drug (P = 0.40).Conclusions: This study showed a prevalence of 11.8% of PI MRV among 110 ART-naive subjects, without significant impact on the virological response to a first-line PI-based regimen containing darunavir or atazanavir. [ABSTRACT FROM AUTHOR]