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Increased HIV drug resistance (HIVDR) with antiretroviral therapy (ART) rollout may jeopardize therapeutic options, especially in this era of transition to fixed-dose tenofovir-lamivudine-dolutegravir (TLD). We studied acquired HIVDR (ADR) patterns and describe potentially active drugs after first- and second-line failure in resource-limited settings (RLS) like Cameroon. A laboratory-based study with 759 patients (≥15 years) experiencing virological failure was carried out at the Chantal Biya International Reference Centre (CIRCB), Yaoundé, Cameroon. Socio-demographic, therapeutic and immunovirological data from patient records were analysed according to HIV-1 genotypic profiles. Median (IQR) ART-duration was 63 (50-308) months. Median CD4 and viremia were 153 (IQR:50-308) cells/mm 3 and 138,666 (IQR:28,979-533,066) copies/mL, respectively. Overall ADR was high (93.4% first-line; 92.9%-second-line). TDF, potentially active in 35.7% of participants after first-line and 45.1% after second-line, suggested sub-optimal TLD-efficacy in second-line (64.3%) and third-line (54.9%). All PI/r preserved high efficacy after first-line failure while only DRV/r preserved high-level efficacy (87.9%) after second-line failure. In this resource-limited setting (RLS), ADR is high in ART-failing patients. PI/r strategies remain potent backbones for second-line ART, while only DRV/r remains very potent despite second-line failure. Though TLD use would be preferable, blind use for second- and third-line regimens may be sub-optimal (functional monotherapy with dolutegravir) with high risk of further failure, thus suggesting strategies for selective ART switch to TLD in failing patients in RLS.

The efficacy of first-line antiretroviral therapy (ART) may be hampered by the presence of HIV drug resistance (HIVDR). We described HIV-1 pre-treatment drug resistance (PDR) patterns, effect of viral clades on PDR, and programmatic implications on first-line regimens in Cameroon. A sentinel surveillance of PDR was conducted from 2014 to 2019. Sequencing of HIV-1 protease and reverse transcriptase was performed, and HIVDR was interpreted using Stanford HIVdb.v.9.4. In total, 379 sequences were obtained from participants (62% female, mean age 36 ± 10 years). The overall PDR rate was 15.0% [95% CI: 11.8-19.0] nationwide, with significant disparity between regions ( p = 0.03). NNRTI PDR was highest (12.4%), of which 7.9% had DRMs to EFV/NVP. Two regions had EFV/NVP PDR above the 10% critical threshold, namely the Far North (15%) and East (10.9%). Eighteen viral strains were identified, predominated by CRF02&#95;AG (65.4%), with no influence of genetic diversity PDR occurrence. TDF-3TC-DTG predictive efficacy was superior (98.4%) to TDF-3TC-EFV (92%), p < 0.0001. The overall high rate of PDR in Cameroon, not substantially affected by the wide HIV-1 genetic diversity, underscores the poor efficacy of EFV/NVP-based first-line ART nationwide, with major implications in two regions of the country. This supports the need for a rapid transition to NNRTI-sparing regimens, with TDF-3TC-DTG having optimal efficacy at the programmatic level.

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.

In Cameroon, local plants are traditionally used as remedies for a variety of ailments. In this regard, several papers report health benefits of Cameroonian spices, which include antioxidant and anti-microbial properties, whereas gastric anti-inflammatory activities have never been previously considered. The present study investigates the antioxidant and anti-inflammatory activities of hydro-alcoholic extracts of eleven Cameroonian spices in gastric epithelial cells (AGS and GES-1 cells). The extracts showed antioxidant properties in a cell-free system and reduced H 2 O 2 -induced ROS generation in gastric epithelial cells. After preliminary screening on TNFα-induced NF-κB driven transcription, six extracts from Xylopia parviflora , Xylopia aethiopica , Tetrapleura tetraptera , Dichrostachys glomerata , Aframomum melegueta , and Aframomum citratum were selected for further studies focusing on the anti-inflammatory activity. The extracts reduced the expression of some NF-κB-dependent pro-inflammatory mediators strictly involved in the gastric inflammatory process, such as IL-8, IL-6, and enzymes such as PTGS2 (COX-2), without affecting PTGS1 (COX-1). In conclusion, the selected extracts decreased pro-inflammatory markers by inhibiting the NF-κB signaling in gastric cells, justifying, in part, the traditional use of these spices. Other molecular mechanisms cannot be excluded, and further studies are needed to better clarify their biological activities at the gastric level.