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Introduction: In low-and-middle-income-countries (LMIC), viral suppression is defined as plasma viral load (PVL) below 1000 copies/mL (low-level viremia [LLV]) and threshold for HIV drug resistance (HIVDR) testing. However, there is evidence that drug resistance mutations (DRMs) may emerge at LLV, thus compromising antiretroviral treatment (ART) response. We evaluated sequencing success rates (SSR) at LLV, described HIVDR profiles and adequacy with potential efficacy of tenofovir-lamivudine-dolutegravir (TLD). Methods: A cross-sectional study was conducted among individuals with LLV at the Chantal BIYA International Reference Centre, Yaoundé, Cameroon from January 2020 through August 2021. HIV-1 sequencing was performed on protease/reverse-transcriptase, and sequences analysed using Stanford HIVdbv9.5. SSR and HIVDR rates were assessed according to viral-load ranges, with P <.05 considered statistically significant. Results: In total, 131 individuals were enrolled (median [IQR] age = 41 [30−49] years; 67.9% female; 54.7% at WHO clinical-stage I/II; median ART-duration 7 [4−11] years; median CD4-count 221 [103−402] cells/mm3 and median PVL 222 [96−436] copies/mL). Overall, SSR at LLV was 34.4% (45/131) and increased significantly with decreasing-age (P =.002) and increasing-PVL (P =.017). SSR were doubled at PVL≥150 copies/mL (21.8% at [40−150] vs. 43.3% at [150−1000]; OR = 2.8, P =.01). Of the 45 sequences obtained, 75.6% were recombinant strains (CRF02_AG, CRF09_cpx, CRF11_cpx) and 24.4% pure-subtypes (A1, D, F2, G). Overall, HIVDR prevalence at LLV was 82.2% (37/45), with 74.6% and 15.6% resistance to reverse-transcriptase inhibitors (RTIs) and ritonavir-boosted protease inhibitors (PI/r) respectively. Interestingly, HIVDR rates were similar at PVLs [50−200] versus [200−1000] copies/mL (P =.69). The most frequent DRMs were M184 V (73.3%) and K103N (40.0%) for RTIs and M46I (6.7%) for PIs/r. Overall 55.6% (25/45) of individuals were on suboptimal ART (needing ART-optimisation), with 48.9% (22/45) having suboptimal TLD predictive efficacy. Optimisation need was higher in first-line (81.8%, P =.03), but similar across viral clades and PVL-ranges (P =.6). Conclusion: In this LMIC context, sequencing for HIVDR is feasible at LLV even with broad HIV-1 diversity, with significantly higher SSR above 150 copies/mL and/or in paediatrics. About 80% of individuals with LLV harbour HIVDR strains, with half of them needing ART optimisations to limit HIVDR emergence and prevent treatment failure. Our findings underscore the clinical benefits of HIVDR during persisting LLV and the need to reconsider the threshold for viral suppression around 200copies/mL in LMICs. Plain Language Summary: Plasma viral load of 200 copies/ml is a suitable threshold to define viral suppression and HIV drug resistance testing in low- and middle-income countries: Evidence from a facility-based study in Cameroon In low- and middle-income countries (LMICs) like Cameroon, virological success is defined as viral loads less than 1000 copies/mL. However, drug-resistant strains can emerge even when viral loads are low and could be challenging for long term management outcomes. This study looked at how well HIV drug resistance (HIVDR) can be detected in people with low viral loads, the rates, and patterns in which they occur and their potential impact on treatment regimens. We found that about one-third of the people could be successfully tested for drug resistance at low viral loads, and this success rate improved significantly with higher viral loads, doubling significantly at a threshold of 150 copies/mL. Up to 80% of those with low viral loads had drug-resistant strains, and about half of them needed their treatment adjusted. This suggests that the current definition of viral suppression (under 1000 copies/ml) might need to be reconsidered and lowered to around 200 copies/ml in LMICs to better control HIV and prevent treatment failure. [ABSTRACT FROM AUTHOR]

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 (<1000 copies/mL) was 96.45%, with 97.08% among I-TLDs versus 95.68% among T-TLDs (p = 0.55). VR was similar in I-TLD versus T-TLD at <400 copies/mL (94.15% versus 94.42%) and age, gender, residence, ART-duration, and WHO stages were not associated with VR (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. [ABSTRACT FROM AUTHOR]

In Cameroon, COVID-19 infection spread rapidly and nationwide, with up to 721 deaths reported. To the best of our knowledge, no study reported the on-theground data using a large patients' dataset to give a comprehensive knowledge on COVID-19 pandemic in Cameroon. The objective of this study was to shade lights on the epidemiological, virological and clinical features of COVID-19 in the Cameroonian context. An observational study was conducted among symptomatic and asymptomatic individuals tested for SARS-CoV-2 by PCR on nasopharyngeal samples from April 22nd, 2020 to January 5th, 2021. Out of 14119 individuals (59.8% male), overall SARS-CoV-2 positivity was 12.7% (from 7.9% in <10 years to 17.3% in >60 years, p<0.001). The positivity rate of symptomatic individuals was 36.1% versus 9.8% among asymptomatic ones, p<0.001. Age group =10 [aOR (95%CI): 0.515 (0.338-0.784), p=0.002] and being symptomatic [aOR (95% CI): 5.108 (4.521-5.771), p<0.001] were predictors of SARS-CoV-2 positivity. Regarding PCR Cycle Threshold (CT), 53.8% of positive individuals had a CT <30. According to age, compared to older individuals, those aged 21-40 years showed a higher proportion with high viraemia (CT<20; 21.3% versus 12.5% respectively, p=0.003). Similarly, symptomatic individuals showed a higher proportion with high viraemia (22.4%), when compared to asymptomatic (13.9%); p<0.001. During this first wave of the pandemic, overall SARS-CoV-2 positivity remained high (>10%) and was associated with the presence of symptoms and older age. Most of the infection is among young and asymptomatic individuals, suggesting the "track-and-test" strategy should target these potential transmitters. [ABSTRACT FROM AUTHOR]

Background: 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.Methods: 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.Results: 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].Conclusions: 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. [ABSTRACT FROM AUTHOR]