Chemokine Coreceptor Usage Among HIV-1 Drug-Naive Patients Residing in the Rural Eastern Cape, South Africa

AIDS Res Hum Retroviruses. 2020 Aug;36(8):688-696. doi: 10.1089/AID.2020.0066. Epub 2020 Jul 9.

Abstract

Sub-Saharan region in Africa still holds the highest burden of HIV/AIDS globally. HIV-1 requires coreceptor to gain entry into permissive cells to initiate infection. Molecular analysis of the chemokine coreceptor usage is important clinically and in the effective management of AIDS virus. This study aims to determine the coreceptor usage among HIV-1 drug-naive patients residing in the rural Eastern cape, South Africa. We collected blood samples from 55 HIV-infected patients into an anticoagulant vacutainer. RNA was extracted from separated plasma, and reverse transcription-polymerase chain reaction (RT-PCR) was performed followed by nested polymerase chain reaction to amplify the partial envelope fragment spanning the C2-C3 region. Sanger sequencing was done on the amplicons using the BigDye Terminator V3.1 sequencing kit (Applied Biosystems, Foster City, CA) while sequences were manually edited using BioEdit and Geneious 10.2.6 tools. The WebPSSM and Geno2pheno online tools were also utilized to predict coreceptor tropism while the phylogenetic analysis of the isolates was determined using MEGA 7. Of the 55 blood samples collected for the study, 50 (91%) were successfully amplified and sequenced. The mean age of the patients was 32 (18-56) years while the ratio of men to women was 35% and 65% correspondingly. Phylogenetic analysis revealed that all 50 sequences clustered with HIV-1 subtype C reference strains. Viral tropism of the V3 loop revealed 47 sequences to be R5 strains, while three sequences (T1E, T10E, and T11E,) were classified as X4 strains based on the WebPSSM and the Geno2pheno algorithm. HIV-1 R5 tropic strains were the most dominant virus obtained from this study, while HIV-1 subtype C still drives the epidemic in South Africa suggesting greater in vivo and host pathogen fitness. Documented data on mapping out cellular tropism based on viral tropism are important as maraviroc and the other CCR5 antagonist could be introduced as part of the treatment regimen in South Africa.

Keywords: CCR5; CXCR4; HIV-1; South Africa; maraviroc; tropism.

MeSH terms

  • Adult
  • Female
  • HIV Infections / epidemiology
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV-1 / classification
  • HIV-1 / genetics*
  • Host-Pathogen Interactions
  • Humans
  • Male
  • Phylogeny
  • RNA, Viral / genetics
  • Receptors, CCR5 / genetics*
  • Receptors, CCR5 / immunology
  • Receptors, CXCR4 / genetics*
  • Receptors, CXCR4 / immunology
  • Rural Population
  • South Africa
  • Viral Tropism*

Substances

  • RNA, Viral
  • Receptors, CCR5
  • Receptors, CXCR4