Circulating HIV-1 Integrase Genotypes in Tanzania: Implication on the Introduction of Integrase Inhibitors-Based Antiretroviral Therapy Regimen

AIDS Res Hum Retroviruses. 2020 Jun;36(6):539-543. doi: 10.1089/AID.2020.0021. Epub 2020 Apr 6.

Abstract

Tanzania has recently adapted World Health Organization antiretroviral guidelines that include integrase strand transfer inhibitors (INSTIs) in the first-line regimen. However, there is lack of evidence on integrase (IN) gene polymorphisms in viral strains circulating in Tanzania. In this study, we characterize IN gene polymorphisms in viral strains circulating in Dar es Salaam, Tanzania, before introduction of INSTIs. Plasma viral RNAs were prepared from 158 HIV-1-infected subjects, including 111 treated, but viremic (INSTI-naïve), subjects. A part of the pol gene encompassing the IN-coding region was amplified and directly sequenced by the Sanger sequencing method. Subtype analysis revealed that subtypes A1, C, and D and intersubtype recombinants were 42%, 38%, 11%, and 9%, respectively. Although multiple subtypes cocirculate, the IN gene exhibited a relatively conserved amino acid sequence pattern with an average Shannon entropy score of 0.16. No major INSTI resistance mutations were found; however, accessory resistance mutations at positions T97A, E157Q, G163E/K, and 128A/T were detected in 5% of subjects.

Keywords: HIV-1; antiretroviral therapy; integrase; mutations; resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiretroviral Therapy, Highly Active / statistics & numerical data*
  • Cross-Sectional Studies
  • Drug Resistance, Viral / genetics
  • Genes, pol / genetics
  • Genotype
  • HIV Infections / blood
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV Integrase / genetics*
  • HIV Integrase Inhibitors / therapeutic use*
  • HIV-1 / drug effects
  • HIV-1 / enzymology
  • HIV-1 / genetics*
  • Humans
  • Mutation
  • Polymorphism, Genetic
  • RNA, Viral / genetics
  • Tanzania

Substances

  • HIV Integrase Inhibitors
  • RNA, Viral
  • HIV Integrase
  • p31 integrase protein, Human immunodeficiency virus 1