HIV-1 Integrase Diversity and Resistance-Associated Mutations and Polymorphisms Among Integrase Strand Transfer Inhibitor-Naive HIV-1 Patients from Cameroon

AIDS Res Hum Retroviruses. 2020 May;36(5):450-455. doi: 10.1089/AID.2019.0264. Epub 2020 Jan 13.

Abstract

The World Health Organization (WHO) has put forth recommendations for the use of integrase (IN) strand transfer inhibitors (INSTIs) to be part of the first-line combination antiretroviral therapy regimen to treat HIV infections. The knowledge of pretreatment drug resistance against INSTIs is still scarce in resource-limited settings (RLS). We characterized the integrase gene to identify resistance-associated mutations (RAMs) in 56 INSTI-naive patient viral sequences from Cameroon. Study analysis used 37 sequences with fragment size ≥500 bp or of good quality .The majority of the sequences were identified as CRF02_AG 54.% (n = 20/37) and 45.9% (n = 17/37), other subtype viral sequences include (A, CRF36_cpx, F,G, and C). A total of 18.9% (n = 7/37) of the sequences had RAMs, with only 5.4% (n = 2/37) having major RAMs (Y143R/C/D/G and P145S), against INSTIs. Accessory RAMs were present in 8.1% (n = 3/37) of the sequences, of which one sequence contained solely E157Q, and another Q95K. One patient sequence had three accessory RAMs (G140E, E157Q, and G163R). We identified major RAMs to INSTIs, which might have a potential clinical impact to dolutegravir rollout in RLS, including Cameroon. This is the first study to describe RAMs among INSTI-naive people living with HIV-1 (PLHIV-1) infected with CRF02_AG and other subtypes in Cameroon.

Keywords: CRF02_AG; Cameroon; HIV-1; diversity; integrase; resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cameroon
  • Cohort Studies
  • Drug Resistance, Viral / genetics
  • Genotype
  • HIV Infections / drug therapy
  • HIV Infections / virology*
  • HIV Integrase / genetics*
  • HIV Integrase Inhibitors / therapeutic use
  • HIV-1 / enzymology
  • HIV-1 / genetics*
  • Humans
  • Mutation*
  • Phylogeny
  • Polymorphism, Genetic*
  • RNA, Viral / genetics
  • Sequence Analysis, DNA

Substances

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