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

Abstract

BackgroundAntiretroviral 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.MethodsThis 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.ResultsOf 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.ConclusionThe 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.

HIV Genetic Diversity, Virological Failure, and Drug Resistance in Libreville, Capital of Gabon, before a Total Dolutegravir-Based Regimen Transition

“…Reverse transcriptase resistance mutations described in this study are in concordance with the previous study in Gabon [4] and Cameroon [27]. This study confirms that TDF has a high genetic barrier and therefore a low level of resistance as described in the literature [27] [31].…”

“…Our studied population is characterized by the dominance of the circulating recombinant form (CRF) subtype. This CRF was previously described as a dominant subtype by previous publications in Gabon [3] [26] and Cameroon [27] [28]. A more recently conducted study in the southeast of Gabon (Franceville, provincial capital of Haut-Ogooué) shows the dominance of HIV-1 subtype "A" followed by "CRF" [4], in agreement with the previous studies conducted in the Republic of Congo, neighboring the province of Haut-Ogooué whose provincial capital is Franceville [29] [30].…”

Phylodynamic analysis in the understanding of the current COVID-19 pandemic and its utility in vaccine and antiviral design and assessment

“…Therefore, the use of the coalescent model would allow the estimation of the effective population size (N e ), which in terms of phylodynamic is proportional to the effective number of infected population, 72 and the assessment of this parameter would help to identify the effect of the introduction of antiviral therapy in the epidemic curve and transmission dynamics. 73 Additionally, although antiviral resistance is more unlikely for an acute virus infection as COVID-19 than for a chronic infection like HIV, the example of anti-retroviral therapy (ART) has shown that evolutionary analysis can be used for the detection of adaptive mutations that if fixed can promote antiviral resistance. 74 This approach could also be used for timely detection of the emergence of drug-resistant strains and the need to switch to a new three-drug regimen (switching therapy).…”

“… 74 This approach could also be used for timely detection of the emergence of drug-resistant strains and the need to switch to a new three-drug regimen (switching therapy). 73 Coupling these data with clinical and epidemiological metadata would help also to identify transmission networks associated with the emergence of resistance in case it happens. 74 …”

Genotypic and pharmacoresistant HIV characteristics in patients in the Socialist Republic of Vietnam

“…Как известно, генотипы ВИЧ имеют свои молекулярно-генетические особенности, сказывающиеся, в том числе, и на чувствительности вируса к препаратам АРВТ [35]. Для генотипа CRF01_AE, наиболее распространенного в СРВ как по литературным данным, так и согласно полученным нами результатам, среди наиболее часто встречающихся мутаций описаны: L33F, M46I, M46L -ассоциированные с лекарственной устойчивостью к ингибиторам протеазы, M41L, A62V, M184V, T215Yк НИОТ, K103N, V108I, G190A -к ННИОТ [36,37].…”