Low-Abundance Resistant Mutations in HIV-1 Subtype C Antiretroviral Therapy-Naïve Individuals as Revealed by Pyrosequencing

Authors

Sandra Gonzalez, University of Nebraska-LincolnFollow
Damien C. Tully, University of Nebraska-Lincoln
Clement Gondwe, University of Nebraska-Lincoln
Charles Wood, University of Nebraska-LincolnFollow

Date of this Version

2013

Citation

Curr HIV Res. 2013 January ; 11(1): 43–49.

Comments

Copyright 2013 Springer. Used by permission.

Abstract

Given the recent scale-up of antiretroviral therapy (ART) in sub-Saharan Africa, we sought to determine how often and at what levels do drug-resistant mutant variants exist in ART-naïve HIV subtype C infected individuals. Samples from 10 ART-naïve Zambian individuals were subjected to ultra-deep pyrosequencing (UDPS) to characterize the frequency of low-abundance drug resistance mutations in the pol gene. Low-abundance clinically relevant variants were detected for nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) in eight of the ten subjects. Intermediate to high-level resistance was predicted for the majority of NRTIs. Mutations conferring resistance to most firstline and some second-line therapy drugs were also observed. UDPS detected a number of additional major resistant mutations suggesting that these individuals may have an increased risk of virological failure after initiating ART. Moreover, the effectiveness of first-line and even some second-line ART may be compromised in this setting.