HIV-1 drug resistance mutations are present in six percent of persons initiating antiretroviral therapy in Lusaka, Zambia

J Acquir Immune Defic Syndr. 2010 Sep;55(1):95-101. doi: 10.1097/QAI.0b013e3181e544e0.

Abstract

Objective: To assess the mutational patterns and factors associated with baseline drug-resistant HIV-1 present at initiation of first-line antiretroviral therapy (ART) at 3 sites in Lusaka, Zambia, in 2007-2008.

Methods: Population sequencing of the HIV-1 pol gene was performed in the PharmAccess African Studies to Evaluate Resistance Monitoring cohort. Drug resistance-associated mutations (DRMs) were identified using the WHO 2009 Surveillance DRM list. Multiple logistic regression was used to assess factors associated with baseline resistance.

Results: The overall prevalence of baseline resistance was 5.7% [31 of 548 participants; 95% confidence interval (CI): 3.9 to 7.9]; the prevalence of DRMs associated with nucleoside reverse transcriptase inhibitors (NRTIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors was 1.1%, 4.0%, and 1.1%, respectively. Resistance prevalence was 5.2% (27 of 523) in antiretroviral-naive and 16.0% (4 of 25) in antiretroviral-experienced (ie, previous use of ART or antiretroviral prophylaxis for prevention of mother-to-child transmission) participants (P = 0.022). Dual-class resistance to NRTIs and NNRTIs was observed in 0.6% of participants. HIV-1 subtype C was identified in 98.0% (537 of 548) of participants. Prior antiretroviral experience (odds ratio: 4.32, CI: 1.34 to 14.0, P = 0.015) and hemoglobin level (highest tertile versus lowest tertile odds ratio: 2.74, CI: 1.09 to 6.89, P = 0.033) were independently associated with baseline resistance.

Conclusions: Baseline resistance may compromise the response to standard NNRTI-based first-line ART in 6% of patients in Lusaka, Zambia. Continuous resistance monitoring is warranted to maintain individual and population-level ART effectiveness.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / pharmacology*
  • Antiretroviral Therapy, Highly Active
  • Drug Resistance, Viral*
  • Female
  • HIV Infections / drug therapy
  • HIV Infections / virology*
  • HIV-1 / drug effects*
  • HIV-1 / genetics
  • HIV-1 / isolation & purification
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Mutation, Missense*
  • Prevalence
  • RNA, Viral / genetics
  • Sequence Analysis, DNA
  • Zambia
  • pol Gene Products, Human Immunodeficiency Virus / genetics

Substances

  • Anti-HIV Agents
  • RNA, Viral
  • pol Gene Products, Human Immunodeficiency Virus

Associated data

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