Observed HIV drug resistance associated mutations amongst naïve immunocompetent children in Yaoundé, Cameroon

Ikomey, George Mondinde; Assoumou, Marie Claire Okomo; Gichana, Josiah Otwoma; Njenda, Duncan; Mikasi, Sello Given; Mesembe, Martha; Lyonga, Emilia; Jacobs, Graeme Brendon

doi:10.18683/germs.2017.1124

Cited by 7 publications

(8 citation statements)

References 15 publications

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“…As previously described [35–37], M184V was the most prevalent NRTI mutation occurring in all the 10 major mutational patterns reported in this study. M184V is associated with high-level resistance to lamivudine and emtricitabine.…”

Section: Discussionsupporting

confidence: 75%

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

et al. 2019

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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.

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Section: Discussionsupporting

confidence: 75%

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

et al. 2019

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“…The estimated global prevalence of pretreatment DRMs was 4% (n=2,719/60,567; range, 2% [Asia Pacific] to 6% [North America]) for those associated with NRTI resistance [16,18,25,28,[30][31][32][35][36][37][38]40,43,44,46,48,49,[51][52][53][54][55][56][57][58][59][60] and 6% (n=3,605/61,402; range, 3% [Asia Pacific] to 8% [Africa and North America]) for those associated with resistance to any NNRTI (Figure 1) [16,18,25,28,[30][31][32][33][34][35][36][37][38][39]41,[70][71][72][73][74][75]…”

Section: Global Prevalence Estimatesmentioning

confidence: 99%

Prevalence of Pretreatment and Acquired HIV-1 Mutations Associated with Resistance to Lamivudine or Rilpivirine: A Systematic Review

et al. 2018

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Background: Pretreatment and acquired drug resistance mutations (DRMs) can limit antiretroviral therapy effectiveness. Methods: We review prevalence of DRMs with resistance to nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs), focusing on lamivudine and rilpivirine, from 127 articles with >100,000 individuals with HIV-1 infection. Results: Estimated global prevalence of pretreatment resistance to any NRTI was 4% and to any NNRTI was 6%.Most prevalent DRMs resistant to lamivudine or rilpivirine were at positions E138 (4%), V179 (1%) and M184 (1%). Estimated acquired DRM prevalence was 58% for any NRTIs and 67% for any NNRTIs, most frequently at positions M184 (58%) and Y181 (21%). Conclusions: This review suggests low risk of lamivudineor rilpivirine-resistant mutations in treatment-naive, HIV-1-infected individuals.

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“…The ability of the HIV-1 virus to mutate during therapy, can lead to the emergence of HIV-1 drug resistance and this necessitates the need for more effective cART regimens with higher genetic barriers [ 1 ]. In Cameroon, the HIV-1 drug resistance rates among cART-initiators stand at approximately, 10% of the Cameroon infected population [ 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations

et al. 2021

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Background The Integrase (IN) strand transfer inhibitor (INSTI), Dolutegravir (DTG), has been given the green light to form part of first-line combination antiretroviral therapy (cART) by the World Health Organization (WHO). DTG containing regimens have shown a high genetic barrier against HIV-1 isolates carrying specific resistance mutations when compared with other class of regimens. Methods We evaluated the HIV-1 CRF02_AG IN gene sequences from Cameroon for the presence of resistance-associated mutations (RAMs) against INSTIs and naturally occurring polymorphisms (NOPs), using study sequences (n = 20) and (n = 287) sequences data derived from HIV Los Alamos National Laboratory database. The possible impact of NOPs on protein structure caused by HIV-1 CRF02_AG variations was addressed within the context of a 3D model of the HIV-1 IN complex and interaction analysis was performed using PyMol to validate DTG binding to the Wild type and seven mutant structures. Results We observed 12.8% (37/287) sequences to contain RAMs, with only 1.0% (3/287) of the sequences having major INSTI RAMs: T66A, Q148H, R263K and N155H. Of these,11.8% (34/287) of the sequences contained five different IN accessory mutations; namely Q95K, T97A, G149A, E157Q and D232N. NOPs occurred at a frequency of 66% on the central core domain (CCD) position, 44% on the C-terminal domain (CTD) position and 35% of the N-terminal domain (NTD) position. The interaction analysis revealed that DTG bound to DNA, 2MG ions and DDE motif residues for T66A, T97A, Q148H, N155H and R263K comparable to the WT structure. Except for accessory mutant structure E157Q, only one MG contact was made with DTG, while DTG had no MG ion contacts and no DDE motif residue contacts for structure D232N. Conclusions Our analysis indicated that all RAM’s that resulted in a change in the number of interactions with encompassing residues does not affect DTG binding, while accessory mutations E157Q and D232N could affect DTG binding leading to possible DTG resistance. However, further experimental validation is required to validate the in silico findings of our study.

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Observed HIV drug resistance associated mutations amongst naïve immunocompetent children in Yaoundé, Cameroon

Cited by 7 publications

References 15 publications

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

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

Prevalence of Pretreatment and Acquired HIV-1 Mutations Associated with Resistance to Lamivudine or Rilpivirine: A Systematic Review

Interaction analysis of statistically enriched mutations identified in Cameroon recombinant subtype CRF02_AG that can influence the development of Dolutegravir drug resistance mutations

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