Analysis of HIV-1 integrase genotypes and polymorphisms among integrase inhibitors-based antiretroviral treatment naïve patients in South Sudan

J Med Virol. 2022 Jul;94(7):3320-3327. doi: 10.1002/jmv.27713. Epub 2022 Mar 26.

Abstract

HIV-1 genetic diversity and drug resistance mutations remain public health challenges especially in regions where treatment is limited. The aim of this study was to characterize the HIV-1 integrase (IN) subtype and the possible occurrence of drug-resistance mutations or polymorphisms in resource-poor settings in South Sudan. Dried blood spots from integrase inhibitor treatment (Integrase strand transfer inhibitor [INSTI]) naïve HIV-1 infected patients were subjected to DNA amplification and direct sequencing of integrase genes. The sequences were interpreted for drug resistance according to the Stanford algorithm and the International AIDS Society-USA guidelines. Phylogenetic analysis revealed that HIV-1 subtype D, C, G, A1, and recombinant forms accounted for 40%, 10%, 13.3%, 23.4%, and 13.3%, respectively. Furthermore, inter-subtype recombinants were interspersed within viral strains sampled in other African countries, highlighting complex transmission dynamics within a mobile host population. A total of 78 of 288 (27%) amino acid IN positions presented at least one polymorphism each. Major INSTI resistance mutations were absent, however, polymorphic accessory mutations at positions M50ILR (26.6%) and L74I (3.3%) were detected. Despite the limited size of the study population, our findings underscore the need for monitoring minor and natural polymorphisms that may influence the outcome of treatment regimens.

Keywords: HIV-1 genotyping; INSTIs; Naïve patients; South Sudan; integrase; resistance mutations.

MeSH terms

  • Anti-HIV Agents* / therapeutic use
  • Drug Resistance, Viral / genetics
  • Genotype
  • HIV Infections* / drug therapy
  • HIV Infections* / epidemiology
  • HIV Integrase Inhibitors* / pharmacology
  • HIV Integrase Inhibitors* / therapeutic use
  • HIV Integrase* / genetics
  • HIV-1*
  • Humans
  • Mutation
  • Phylogeny
  • South Sudan

Substances

  • Anti-HIV Agents
  • HIV Integrase Inhibitors
  • HIV Integrase
  • p31 integrase protein, Human immunodeficiency virus 1