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 journalArticle

8 Citations (Scopus)

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
StatePublished - Apr 30 2013

Fingerprint

HIV-1
Reverse Transcriptase Inhibitors
Mutation
Nucleosides
pol Genes
Therapeutics
Africa South of the Sahara
Protease Inhibitors
Drug Resistance
HIV
Drug Therapy
Pharmaceutical Preparations

Keywords

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

ASJC Scopus subject areas

  • Infectious Diseases
  • Virology

Cite this

Low-abundance resistant mutations in HIV-1 subtype c antiretroviral therapy-naïve individuals as revealed by pyrosequencing. / Gonzalez, Sandra; Tully, Damien C.; Gondwe, Clement; Wood, Charles.

In: Current HIV research, Vol. 11, No. 1, 30.04.2013, p. 43-49.

Research output: Contribution to journalArticle

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