Prevalence of integrase strand transfer inhibitor resistance mutations in antiretroviral-naive HIV-1-infected individuals in Cameroon.

In Cameroon, the integrase (IN) strand transfer inhibitor (INSTI) dolutegravir was recently introduced for the treatment of HIV-1 infection. Since pretreatment HIV-1 drug resistance can jeopardize the success of ART, and considering the high heterogeneity of circulating HIV-1 subtypes in Cameroon, we investigated the prevalence of pretreatment HIV-1 resistance to INSTIs. Fingerprick dried blood spot samples were collected from 339 newly diagnosed HIV-1-infected individuals between 2015 and 2016 in four hospitals in Cameroon. Universal primers were designed to amplify the HIV-1 IN region from amino acid 1 to 276. Amplicons were sequenced with Illumina next-generation sequencing and analysed with the Polymorphism Analysis Sequencing (PASeq) platform, using the Stanford HIV Drug Resistance Database to interpret HIV-1 drug resistance mutations (DRMs). The amplification/sequencing success rate was 75.2% with 255/339 sequences obtained. Applying a cut-off of 1%, major DRMs to INSTIs were detected in 13 (5.1%) individuals, but only 1 individual harboured an INSTI DRM (E92G) at a nucleotide frequency ≥15%. However, 140/255 (54.9%) individuals harboured polymorphic accessory INSTI DRMs, mainly at high frequencies. In line with that observation, HIV-1 subtype diversity among individuals was high. Pretreatment HIV-1 resistance to INSTIs was low in the study sites, which supports the use of INSTIs in Cameroon. Nevertheless, further studies are necessary to assess the impact of polymorphic accessory INSTI DRMs on INSTI-based ART regimens.

Wenk BM ，Mbunkah HA ，Nsanwe NN ，Mbu ET ，Besong LM ，Sama BA ，Orock E ，Leemann C ，Metzner KJ ... -  《-》

Baseline integrase drug resistance mutations and conserved regions across HIV-1 clades in Cameroon: implications for transition to dolutegravir in resource-limited settings.

Transition to dolutegravir-based regimens in resource-limited settings (RLS) requires prior understanding of HIV-1 integrase variants and conserved regions. Therefore, we evaluated integrase drug resistance mutations (DRMs) and conserved regions amongst integrase strand transfer inhibitor (INSTI)-naive patients harbouring diverse HIV-1 clades in Cameroon. A cross-sectional study was conducted amongst 918 INSTI-naive patients from Cameroon (89 ART-naive and 829 ART-experienced patients). HIV-1 sequences were interpreted regarding INSTI-DRMs using the Stanford HIVdb v8.9-1 and the 2019 IAS-USA list. Amino acid positions with <1% variability were considered as highly conserved. Subtyping was performed by phylogeny. Overall prevalence (95% CI) of INSTI-DRMs was 0.8% (0.4-1.7), with 0.0% (0.0-4.0) amongst ART-naive versus 0.9% (0.5-1.9) amongst ART-experienced patients; P = 0.44. Accessory mutations (95% CI) were found in 33.8% (30.9-37.0), with 38.2% (28.1-49.1) amongst ART-naive versus 33.4% (30.4-36.7) amongst ART-experienced patients; P = 0.21. Of 288 HIV-1 integrase amino acid positions, 58.3% were highly conserved across subtypes in the following major regions: V75-G82, E85-P90, H114-G118, K127-W132, E138-G149, Q168-L172, T174-V180, W235-A239 and L241-D253. Wide genetic diversity was found (37 clades), including groups M (92.3%), N (1.4%), O (6.2%) and P (0.1%). Amongst group M, CRF02_AG was predominant (47.4%), with a significantly higher frequency (95% CI) of accessory mutations compared with non-AG [41.4% (36.8-46.0) versus 27.1% (23.3-31.2) respectively; P < 0.001]. The low baseline of INSTI-DRMs (<1%) in Cameroon suggests effectiveness of dolutegravir-based regimens. In spite of high conservation across clades, the variability of accessory mutations between major circulating strains underscores the need for monitoring the selection of INSTI-DRMs while scaling up dolutegravir-based regimens in RLS.

Semengue ENJ ，Armenia D ，Inzaule S ，Santoro MM ，Dambaya B ，Takou D ，Teto G ，Nka AD ，Yagai B ，Fabeni L ，Chenwi C ，Angong Beloumou G ，Djupsa Ndjeyep SC ，Colizzi V ，Perno CF ，Ceccherini-Silberstein F ，Fokam J ... -  《-》

Integrase Strand Transfer Inhibitor Resistance in Integrase Strand Transfer Inhibitor-Naive Persons.

Bailey AJ ，Rhee SY ，Shafer RW 《-》

HIV-1 Integrase Diversity and Resistance-Associated Mutations and Polymorphisms Among Integrase Strand Transfer Inhibitor-Naive HIV-1 Patients from Cameroon.

Mikasi SG ，Gichana JO ，Van der Walt C ，Brado D ，Obasa AE ，Njenda D ，Messembe M ，Lyonga E ，Assoumou O ，Cloete R ，Ikomey GM ，Jacobs GB ... -  《-》

HIV-1 diversity and pre-treatment drug resistance in the era of integrase inhibitor among newly diagnosed ART-naïve adult patients in Luanda, Angola.

The surveillance of drug resistance in the HIV-1 naïve population remains critical to optimizing the effectiveness of antiretroviral therapy (ART), mainly in the era of integrase strand transfer inhibitor (INSTI) regimens. Currently, there is no data regarding resistance to INSTI in Angola since Dolutegravir-DTG was included in the first-line ART regimen. Herein, we investigated the HIV-1 genetic diversity and pretreatment drug resistance (PDR) profile against nucleoside/tide reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and INSTIs, using a next-generation sequencing (NGS) approach with MinION, established to track and survey DRMs in Angola. This was a cross-sectional study comprising 48 newly HIV-diagnosed patients from Luanda, Angola, screened between March 2022 and May 2023. PR, RT, and IN fragments were sequenced for drug resistance and molecular transmission cluster analysis. A total of 45 out of the 48 plasma samples were successfully sequenced. Of these, 10/45 (22.2%) presented PDR to PIs/NRTIs/NNRTIs. Major mutations for NRTIs (2.2%), NNRTIs (20%), PIs (2.2%), and accessory mutations against INSTIs (13.3%) were detected. No major mutations against INSTIs were detected. M41L (2%) and I85V (2%) mutations were detected for NRTI and PI, respectively. K103N (7%), Y181C (7%), and K101E (7%) mutations were frequently observed in NNRTI. The L74M (9%) accessory mutation was frequently observed in the INSTI class. HIV-1 pure subtypes C (33%), F1 (17%), G (15%), A1 (10%), H (6%), and D (4%), CRF01_AG (4%) were observed, while about 10% were recombinant strains. About 31% of detected HIV-1C sequences were in clusters, suggesting small-scale local transmission chains. No major mutations against integrase inhibitors were detected, supporting the continued use of INSTI in the country. Further studies assessing the HIV-1 epidemiology in the era of INSTI-based ART regimens are needed in Angola.

Sebastião CS ，Abecasis AB ，Jandondo D ，Sebastião JMK ，Vigário J ，Comandante F ，Pingarilho M ，Pocongo B ，Cassinela E ，Gonçalves F ，Gomes P ，Giovanetti M ，Francisco NM ，Sacomboio E ，Brito M ，Neto de Vasconcelos J ，Morais J ，Pimentel V ... -  《Scientific Reports》