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Current HIV Research

Editor-in-Chief

ISSN (Print): 1570-162X
ISSN (Online): 1873-4251

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

Author(s): Sandra Gonzalez, Damien C. Tully, Clement Gondwe and Charles Wood

Volume 11, Issue 1, 2013

Page: [43 - 49] Pages: 7

DOI: 10.2174/1570162X11311010006

Price: $65

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-naive HIV subtype C infected individuals. Samples from 10 ART-naive 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 first-line 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 secondline ART may be compromised in this setting.

Keywords: Antiretroviral therapy, drug naive, HIV-1, low abundance variants, subtype C, ultra-deep pyrosequencing, Zambia, NRTIs, UDPS, PIs


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