Variability in HIV-1 Integrase Gene and 3'-Polypurine Tract Sequences in Cameroon Clinical Isolates, and Implications for Integrase Inhibitors Efficacy

Int J Mol Sci. 2020 Feb 25;21(5):1553. doi: 10.3390/ijms21051553.

Abstract

: Integrase strand-transfer inhibitors (INSTIs) are now included in preferred first-line antiretroviral therapy (ART) for HIV-infected adults. Studies of Western clade-B HIV-1 show increased resistance to INSTIs following mutations in integrase and nef 3'polypurine tract (3'-PPT). With anticipated shifts in Africa (where 25.6-million HIV-infected people resides) to INSTIs-based ART, it is critical to monitor patients in African countries for resistance-associated mutations (RAMs) affecting INSTIs efficacy. We analyzed HIV-1 integrase and 3'-PPT sequences in 345 clinical samples from INSTIs-naïve HIV-infected Cameroonians for polymorphisms and RAMs that affect INSTIs. Phylogeny showed high genetic diversity, with the predominance of HIV-1 CRF02_AG. Major INSTIs RAMs T66A and N155K were found in two (0.6%) samples. Integrase polymorphic and accessory RAMs found included T97A, E157Q, A128T, M50I, S119R, L74M, L74I, S230N, and E138D (0.3%-23.5% of samples). Ten (3.2%) samples had both I72V+L74M, L74M+T97A, or I72V+T97A mutations; thirty-one (9.8%) had 3'-PPT mutations. The low frequency of major INSTIs RAMs shows that INSTIs-based ART can be successfully used in Cameroon. Several samples had 1 INSTIs accessory RAMs known to reduce INSTIs efficacy; thus, INSTIs-based ART would require genetic surveillance. The 3'-PPT mutations could also affect INSTIs. For patients failing INSTIs-based ART with no INSTIs RAMs, monitoring 3'-PPT sequences could reveal treatment failure etiology.

Keywords: 3’polypurine tract; Cameroon; HIV; antiretroviral drugs; integrase inhibitors; resistance-associated mutations.

MeSH terms

  • Adult
  • Cameroon
  • Drug Resistance, Viral*
  • Female
  • HIV Infections / drug therapy
  • HIV Infections / virology*
  • HIV Integrase / genetics*
  • HIV Integrase Inhibitors / therapeutic use*
  • HIV-1 / enzymology
  • HIV-1 / genetics*
  • HIV-1 / pathogenicity
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Nucleotide Motifs
  • Polymorphism, Genetic*

Substances

  • HIV Integrase Inhibitors
  • HIV Integrase