High Level of Pre-Treatment HIV-1 Drug Resistance and Its Association with HLA Class I-Mediated Restriction in the Pumwani Sex Worker Cohort

Viruses. 2022 Jan 28;14(2):273. doi: 10.3390/v14020273.

Abstract

Background: We analyzed the prevalence of pre-antiretroviral therapy (ART) drug resistance mutations (DRMs) in a Kenyan population. We also examined whether host HLA class I genes influence the development of pre-ART DRMs.

Methods: The HIV-1 proviral DNAs were amplified from blood samples of 266 ART-naïve women from the Pumwani Sex Worker cohort of Nairobi, Kenya using a nested PCR method. The amplified HIV genomes were sequenced using next-generation sequencing technology. The prevalence of pre-ART DRMs was investigated. Correlation studies were performed between HLA class I alleles and HIV-1 DRMs.

Results: Ninety-eight percent of participants had at least one DRM, while 38% had at least one WHO surveillance DRM. M184I was the most prevalent clinically important variant, seen in 37% of participants. The DRMs conferring resistance to one or more integrase strand transfer inhibitors were also found in up to 10% of participants. Eighteen potentially relevant (p < 0.05) positive correlations were found between HLA class 1 alleles and HIV drug-resistant variants.

Conclusions: High levels of HIV drug resistance were found in all classes of antiretroviral drugs included in the current first-line ART regimens in Africa. The development of DRMs may be influenced by host HLA class I-restricted immunity.

Keywords: antiretroviral therapy; drug-resistant mutation; human immunodeficiency virus; human leukocyte antigen; next-generation sequencing technology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alleles
  • Anti-HIV Agents / pharmacology*
  • Cohort Studies
  • Drug Resistance, Viral / genetics*
  • Female
  • Genes, MHC Class I*
  • HIV Infections / drug therapy
  • HIV Infections / genetics
  • HIV Infections / virology*
  • HIV-1 / drug effects*
  • HIV-1 / genetics
  • Humans
  • Kenya
  • Mutation
  • Sex Workers*
  • Young Adult

Substances

  • Anti-HIV Agents