Genetic diversity and antiretroviral resistance-associated mutation profile of treated and naive HIV-1 infected patients from the Northwest and Southwest regions of Cameroon

PLoS One. 2019 Nov 21;14(11):e0225575. doi: 10.1371/journal.pone.0225575. eCollection 2019.

Abstract

Background: Antiretroviral therapy (ART) has improved the survival of HIV infected persons. However, rapid scale-up of ART and the high HIV-1 genetic variability, has greatly influenced the emergence of drug-resistant strains. This constitutes a potential threat to achieving the UNAIDS' 90-90-90 goals by 2020. We investigated the prevalent HIV-1 genotypes, drug resistance-associated mutations and assessed some predictors of the occurrence of these mutations.

Methods: This was a hospital-based cross-sectional study conducted between October 2010 and June 2012. Participants were consecutively enrolled from selected HIV treatment centers of the Southwest and Northwest regions of Cameroon. Viral load was determined with the automated Abbott Real-time HIV-1 m2000rt System. HIV genotyping and antiretroviral resistance mutations analysis were performed using Bayer's HIV-1 TRUGENE™ Genotyping Kit and OpenGene DNA Sequencing system. The drug resistance mutation was interpreted with the Stanford HIV database. Epidemiological data were obtained using pre-tested semi-structured questionnaires.

Results: Of the 387 participants, 239 were successfully genotyped. The median age of these participants was 33 years (interquartile range, IQR: 28-40 years), and a majority (65.7%) were female. A total of 29.3% of the participants were receiving ART. The median duration of ART was 10.5 months (IQR: 4-17.25 months). The median CD4 count and log10 viral load of study participants were 353.5 cells/ml (IQR:145-471) and 4.89 copies/ml (IQR: 3.91-5.55) respectively. CRF02 (A/G) (69%) was the most prevalent subtype followed by G (8.2%) and F (6.7%). Overall, resistance mutations were present in 37.1% of ART-experienced and 10.7% of ART-naive patients. Nucleoside reverse transcriptase inhibitors (NRTI) mutations occurred in 30% of ART-experienced and 2.4% of ART-naïve patients, while non-nucleoside reverse transcriptase inhibitors (NNRTI) mutations occurred in 34.2% of ART-experienced and 10.1% of -naïve patients. M184V (8.4%, 20/239) and K103N (5.4%, 13/239) were the most prevalent mutations. Major protease inhibitor mutations occurred in 3 (1.3%) out of the 239 sequences. The duration of ART independently predicted the occurrence of resistance mutation among ART-experienced patients.

Conclusion: The high resistance to NNRTIs, which are the main support to the backbone (NRTIs) first-line antiretroviral regimen in Cameroon, has prompted the need to rollout an integrase strand transfer inhibitor regimen (containing Dolutegravir) with a higher genetic barrier to resistance as the preferred first line regimen.

MeSH terms

  • Adult
  • Anti-HIV Agents / pharmacology
  • Anti-HIV Agents / therapeutic use
  • Cameroon
  • Cross-Sectional Studies
  • Drug Resistance, Viral*
  • Female
  • Genotype
  • HIV Infections / drug therapy
  • HIV Infections / virology*
  • HIV-1 / drug effects
  • HIV-1 / genetics*
  • HIV-1 / physiology
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Phylogeny
  • Reverse Transcriptase Inhibitors / pharmacology
  • Reverse Transcriptase Inhibitors / therapeutic use*
  • Viral Load

Substances

  • Anti-HIV Agents
  • Reverse Transcriptase Inhibitors

Grants and funding

The author(s) received no specific funding for this work. Henry Dilonga Meriki is affiliated to BioCollections Worldwide Inc. BioCollections Worldwide Inc. provided support in the form of consultancy fees for author HDM as Country manager, data and sample collection and laboratory analysis, but did not have any additional role in the study design, analysis, decision to publish, or preparation of the manuscript. The specific roles of this author is articulated in the ‘author contributions’ section.