Low-abundance resistant mutations in HIV-1 subtype c antiretroviral therapy-naïve individuals as revealed by pyrosequencing

Sandra Gonzalez, Damien C. Tully, Clement Gondwe, Charles Wood

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)43-49
Number of pages7
JournalCurrent HIV research
Volume11
Issue number1
DOIs
StatePublished - 2013

Keywords

  • Antiretroviral therapy
  • Drug naïve
  • HIV-1
  • Low abundance variants
  • Subtype C
  • Ultra-deep pyrosequencing
  • Zambia

ASJC Scopus subject areas

  • Infectious Diseases
  • Virology

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