Viral tropism and antiretroviral drug resistance in HIV-1 subtype C-infected patients failing highly active antiretroviral therapy in Johannesburg, South Africa

AIDS Res Hum Retroviruses. 2014 Mar;30(3):289-93. doi: 10.1089/AID.2013.0267. Epub 2013 Dec 13.

Abstract

Reports show that up to 30% of antiretroviral drug-naive patients in Johannesburg have CXCR4-utilizing HIV-1 subtype C. We assessed whether HIV-1 subtype C-infected individuals failing highly active antiretroviral therapy (HAART) have a higher proportion of CXCR4-utilizing viruses compared to antiretroviral drug-naive patients. The V3 loop was sequenced from plasma from 100 randomly selected HAART-failing patients, and tropism was established using predictive algorithms. All patients harbored HIV-1 subtype C with at least one antiretroviral drug resistance mutation. Viral tropism prediction in individuals failing HAART revealed similar proportions (29%) of X4-utilizing viruses compared to antiretroviral drug-naive patients (30%). Findings are in contrast to reports from Durban in which 60% of HAART-failing subjects harbored X4/dual/mixed-tropic viruses. Despite differences in proportions of X4-tropism within South Africa, the high proportion of thymidine analogue mutations (TAMs) and CXCR4-utilizing HIV-1 highlights the need for intensified monitoring of HAART patients and the predicament of diminishing drug options, including CCR5 antagonists, for patients failing therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Retroviral Agents / pharmacology
  • Anti-Retroviral Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active / methods*
  • Drug Resistance, Viral*
  • Genotype
  • HIV Infections / drug therapy
  • HIV Infections / virology*
  • HIV-1 / drug effects*
  • HIV-1 / genetics
  • HIV-1 / isolation & purification
  • HIV-1 / physiology*
  • Humans
  • Molecular Sequence Data
  • Mutation, Missense
  • RNA, Viral / genetics
  • Receptors, HIV / metabolism
  • Sequence Analysis, DNA
  • South Africa
  • Treatment Failure
  • Viral Tropism*

Substances

  • Anti-Retroviral Agents
  • RNA, Viral
  • Receptors, HIV

Associated data

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