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


Autoři: Henry Dilonga Meriki aff001;  Kukwah Anthony Tufon aff001;  Damian Nota Anong aff001;  Pascal Nji Atanga aff004;  Irene Ane Anyangwe aff001;  Fidelis Cho-Ngwa aff005;  Theresa Nkuo-Akenji aff001
Působiště autorů: Department of Microbiology and Parasitology, University of Buea, Buea, SW Region, Cameroon aff001;  BioCollections Worldwide Inc., Regional Office, Buea, SW Region, Cameroon aff002;  Department of Biochemistry and Molecular Biology, University of Buea, Buea, SW Region, Cameroon aff003;  Cameroon Baptist Convention Health Service, Mutengene, South West Region, Cameroon aff004;  Laboratory Department, Buea Regional Hospital, Buea, SW Region, Cameroon aff005
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: 10.1371/journal.pone.0225575

Souhrn

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.

Klíčová slova:

Antimicrobial resistance – Antiretrovirals – HIV-1 – Mutation databases – Viral load – Reverse transcriptase inhibitors


Zdroje

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