Evaluation of HIV-1 capsid genetic variability and lenacapavir (GS-6207) drug resistance-associated mutations according to viral clades among drug-naive individuals

Objectives We evaluated the HIV-1 capsid genetic variability and lenacapavir drug resistance-associated mutations (DRMs) among drug-naive individuals across HIV-1 clades. Methods A total of 2031 HIV-1 sequences from drug-naive patients were analysed for capsid amino acid modification and the prevalence of lenacapavir DRMs. Amino acid positions with Results Overall, 63% (148/232) of amino acid positions were conserved in the capsid protein. Of note, conservation was consistent in specific binding residues of cellular factors involved in viral replication [CypA (G89, P90), CPSF6 (Q4, N57, N74, A77, K182) and TRIM-NUP153 (R143)], while N183 (12.31%) was the only non-conserved lenacapavir binding residue. The overall prevalence (95% CI) of lenacapavir DRMs was 0.14% (0.05-0.44) (3/2031), with M66I (0.05%) and Q67H (0.05%) observed in subtype C, and T107N (0.05%) observed in CRF01_AE. Moreover, polymorphic mutations M66C (n = 85; 4.18%), Q67K (n = 78; 3.84%), K70R (n = 7; 0.34%), N74R (n = 57; 2.81%) and T107L (n = 82; 4.03%) were observed at lenacapavir resistance-associated positions. Conclusions The low level of lenacapavir DRMs (<1%) supports its predicted effectiveness for treatment and prevention, regardless of HIV-1 clades. The established conserved regions hence serve as a hallmark for the surveillance of novel mutations potentially relevant for lenacapavir resistance

COVID-19 preventive social-behavioural practices and exposure to SARS-CoV-2 among residents in the city of Yaounde: Lessons from the early phase of the pandemic in Cameroon

Non-pharmaceutical interventions remain key in mitigating the spread of SARS-CoV-2. We sought to assess COVID-19 preventive, social-behavioural practices, and SARS-CoV-2 exposure through IgG rapid tests. This was a cross-sectional survey among 971 respondents residing in 180 households within the “Cite Verte” health district of Yaounde-Cameroon, from October-November 2020. Using a structured questionnaire, data on SARS-CoV-2 preventive and social behavioural practices were collected, while exposure to SARS-CoV-2 was determined by IgG profiling. p<0.05 was considered statistically significant. Overall, 971 participants were enrolled, among whom 56.5% were females. The age group 15–29 (33.5%) and those with a secondary level of education (44.7%) were most represented. Regarding preventive/social behavioural practices, the least respected measure was "stopped work", 49.1%, while the most respected was "Respect of hygiene rules", 93.8%. Women obeyed preventive measures more than men, with 87.6% vs 81.0% adhering to the lockdown, (p = 0.005) and 95.5% vs 91.7% to hygiene rules (p = 0.017). The age range 45–64 years was the least adherent to the lockdown rule, with 75.2% (38/153), p<0.0001. Only 24.7% (73/295) and 6.1% (59/295) of the symptomatic individuals reported having sought medical consultation and Covid-19 testing respectively. In addition, up to 69.8% (555/795) felt healthcare facilities were high-risk sites for getting infected, p = 0.002. Exposure to SARS-CoV-2 by IgG positivity was 31.1% (302/971), with men recording a higher proportion of viral exposure, 51.0% (154/302), p = 0.021. After adjusting for gender, age, education, and occupation; salaried worker (p = 0.029; OR: 0.29), and trading (p = 0.001; OR: 0.23) least complied with lockdown rule. In this community of Cameroonian residents highly exposed to COVID-19, many perceived healthcare facilities as high-risk zones for SARS-CoV-2 infection and consequently did not seek medical interventions. Thus, in the context of such a pandemic, advocacy on risk communication and community engagement for health-seeking attitudes should preferentially target men and those afraid of pandemics

Dolutegravir-Based Regimen Ensures High Virological Success despite Prior Exposure to Efavirenz-Based First-LINE ART in Cameroon: An Evidence of a Successful Transition Model

To ensure optimal prescribing practices in the dolutegravir-era in Cameroon, we compared first-line virological response (VR) under tenofovir + lamivudine + dolutegravir (TLD) according to prior exposure to tenofovir + lamivudine + efavirenz (TLE). A facility-based survey was conducted among patients initiating antiretroviral therapy (ART) with TLD (I-TLD) versus those transitioning from TLE to TLD (T-TLD). HIV viral load was performed and unsuppressed participants (VL > 1000 copies/mL) had genotyping performed by Sanger sequencing. Of the 12,093 patients followed, 310 (mean-age: 41 ± 11 years; 52.26% female) complied with study criteria (171 I-TLD vs. 139 T-TLD). The median ART-duration was 14 (12–17) months among I-TLDs versus 28 (24.5–31) months among T-TLDs (15 (11–19) on TLE and 14 (9–15) on TLD), and 83.15% (148/178) were at WHO clinical stages I/II. The viral suppression rate (p = 0.55). VR was similar in I-TLD versus T-TLD at p > 0.05). Genotyping was successful for 72.7% (8/11), with no major mutations to integrase inhibitors found. VR is optimal under first-line TLD after 14 months, even among TLE-exposed, thus confirming the effectiveness of transitioning from TLE to TLD in similar settings, supported by strong pharmacological potency and genetic barrier of dolutegravir

Evaluation of Circulating and Archived HIV-1 Integrase Drug-Resistance Variants among Patients on Third-Line ART in Cameroon: Implications for Dolutegravir-Containing Regimens in Resource-Limited Settings

We described the analysis of the genotypes of the population within third-line antiviral therapy in Cameroon, with a focus on defining the effects of prior raltegravir (RAL) treatment and resistance mutations for current dolutegravir (DTG) treatment. While supporting the current transition to DTG-containing ART in resource-limited settings toward the achievement of the UNAIDS' goal of HIV elimination by 2030, our findings suggested that RAL-exposed patients may need a specific monitoring approach either in a stratified or personalized model of third-line ART to ensure the long-term success of DTG-containing regimens.To ensure the long-term efficacy of dolutegravir (DTG), we evaluated the genotypic profile in viral reservoirs among patients on third-line (3L) antiretroviral therapy (ART) in Cameroon, according to prior exposure to raltegravir (RAL). A facility-based study was conducted from May through December 2021 among patients on 3L ART from HIV treatment centers in Yaounde and Douala. Viral load was measured, and genotyping was performed on plasma RNA and proviral DNA. HIV-1 drug resistance mutations were interpreted using HIVdb.v9.1 and phylogeny analysis was performed using MEGA.v7, with P &lt; 0.05 considered significant. Of the 12,093 patients on ART, 53 fully met our inclusion criteria. The median (IQR) age was 51 years (40 to 55 years), and the male/female ratio was 4/5. The median duration on integrase strand-transfer inhibitors (INSTI)-containing regimens was 18 months (12 to 32 months), and 15.09% (8/53) were exposed to RAL. The most administered 3L ART was TDF+3TC+DTG+DRV/r (33.96%, 18/53). Only 5.66% (3/53) had unsuppressed viremia (&gt;1000 copies/mL). Resistance testing in proviral DNA was successful for 18/22 participants and revealed 1/18 patients (5.56%, in the RAL-arm) with archived mutations at major resistance positions (G140R and G163R). Five subtypes were identified, CRF02_AG (12/18), CRF22_01AE (3/18), A1 (1/18), G (1/18), and F2 (1/18). In Cameroon, 3L-experienced patients had a good virological response with a low level of archived mutations in the integrase. This finding underscored the use of DTG-containing ART for heavily treated patients in similar programmatic settings. However, patients with prior exposure to RAL should be closely monitored following a stratified or personalized approach to mitigate risks of INSTI-resistance, alongside pharmacovigilance. IMPORTANCE We described the analysis of the genotypes of the population within third-line antiviral therapy in Cameroon, with a focus on defining the effects of prior raltegravir (RAL) treatment and resistance mutations for current dolutegravir (DTG) treatment. While supporting the current transition to DTG-containing ART in resource-limited settings toward the achievement of the UNAIDS' goal of HIV elimination by 2030, our findings suggested that RAL-exposed patients may need a specific monitoring approach either in a stratified or personalized model of third-line ART to ensure the long-term success of DTG-containing regimens