Connection domain mutations during antiretroviral treatment failure in Mali: frequencies and impact on reverse transcriptase inhibitor activity

J Acquir Immune Defic Syndr. 2012 Nov 1;61(3):293-6. doi: 10.1097/QAI.0b013e31826a4b34.

Abstract

Mutations in the connection domain (CD) of reverse transcriptase have been implicated in reverse transcriptase inhibitor (RTI) resistance, but this is controversial and little is known in non-B subtype HIV-1. We determined CD mutations prevalence in a population infected predominantly with CRF02_AG and investigated associations with phenotypic RTI resistance. Detected CD mutations were G335D (82.3%), A371V (69.8%), E399D (9.4%), N348I (5.2%), V365I (4.2), Y318F (2.1%), G333E (2.1%), and A360V (2.1%). Mutations were largely polymorphic and did not confer RTI resistance. The observed trend toward reduced likelihood of etravirine or nevirapine resistance in the presence of G335D should be investigated further.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkynes
  • Anti-HIV Agents / therapeutic use*
  • Benzoxazines / pharmacology
  • Benzoxazines / therapeutic use
  • Binding Sites / drug effects
  • Binding Sites / genetics
  • Cyclopropanes
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / pharmacology
  • Deoxycytidine / therapeutic use
  • Drug Resistance, Viral / genetics
  • Emtricitabine
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV Reverse Transcriptase / antagonists & inhibitors
  • HIV Reverse Transcriptase / genetics*
  • HIV-1 / drug effects
  • HIV-1 / enzymology
  • HIV-1 / genetics
  • Humans
  • Mali
  • Mutation / genetics
  • Nevirapine / pharmacology
  • Nevirapine / therapeutic use
  • Phenotype
  • Treatment Failure

Substances

  • Alkynes
  • Anti-HIV Agents
  • Benzoxazines
  • Cyclopropanes
  • Deoxycytidine
  • Nevirapine
  • HIV Reverse Transcriptase
  • Emtricitabine
  • efavirenz