Introduction Globally, HIV‐related adolescent deaths have increased about 50%, especially for those who are vertically infected. This could be driven by archived drug resistance mutations (DRMs) as children grow up, which might jeopardize antiretroviral therapy (ART). Our objective was to compare HIV‐1 genotypic variation between plasma RNA and proviral DNA of vertically infected adolescents (aged 10–19 years) failing ART. Methods A comparative study was conducted in 2019 among 296 adolescents with perinatal HIV infection (ALPHI) failing ART in health facilities of the Centre Region of Cameroon. The WHO clinical stage, CD4 count and plasma viral load (PVL) were measured. For those failing ART (PVL ≥ 1000 copies/mL), RNA (plasma) and proviral DNA (buffy coat) were sequenced in the pol gene at Chantal BIYA International Reference Centre (CIRCB), Yaoundé, Cameroon. HIV‐1 subtypes and DRMs were interpreted using Stanford HIVdb v.8.8 and MEGA‐X. Results Of the 30% (89/296) failing ART, 81 had both RNA and DNA sequences generated and three were excluded for APOBEC mutations: the mean age was 16 ± 3 years; female‐to‐male ratio was 3:5; median PVL was 46 856 copies/mL [interquartile range (IQR): 19 898–271 410]; median CD4 count was 264 cells/μL (IQR: 131–574); and 42% were at WHO clinical stage 3/4. Subtype concordance between RNA and DNA viral strains was 100%, with CRF02_AG being predominant (65%) and two potential new recombinants found (A1/G/K; F1/G). Adolescents with DRMs were significantly higher in plasma than in proviral DNA (92% vs. 86%, p < 0.0001). Prevalent DRMs by drug class (RNA vs. DNA respectively) were at position M184 (74% vs. 67%) for nucleoside reverse transcriptase inhibitors (NRTIs), K103 (63% vs. 59%) for non‐NRTIs, and V82, L76 and M46 (2% vs. 2%) for protease inhibitors. A total of 35% (27/78) of adolescents had concordant DRM profiles in RNA and DNA, while 27% (21/78) had DRMs only in proviral DNA. The presence of archived DRMs was associated with advanced clinical stage 3/4 (OR = 0.14, p = 0.0003) and PVL < 5 Log (Copies/mL) (OR: 4.88, p = 0.006). Conclusions Although plasma RNA remains more sensitive for detecting HIV‐1 DRMs, about a quarter of ALPHI experiencing ART failure in an African setting might have archived DRMs in viral reservoirs, indicating clinically occult resistance. Thus, to ensure effective ART success, proviral DNA profiling (alongside RNA genotyping) would provide additional DRMs for adolescents with advanced clinical stages and/or moderate PVL.

Background With the scale-up of antiretroviral therapy (ART), pre-treatment drug resistance (PDR) appears �10% amongst ART-initiators in many developing countries, including Cameroon. Northwest region-Cameroon having the second epidemiological burden of HIV infection, generating data on PDR in these geographical settings, will enhance evidence-based decision-making. Objectives We sought to ascertain levels of PDR and HIV-1 clade dispersal in rural and urban settings, and their potential association with subtype distribution and CD4-staging. Methods A cross-sectional study was conducted from February to May 2017 among patients recently diagnosed with HIV-infection and initiating ART at the Bamenda regional Hospital (urban setting) and the Mbingo Baptist hospital (rural setting). Protease and reverse transcriptase sequencing was performed using an in-house protocol and pre-treatment drug resistance mutations were interpreted using Stanford HIVdb.v8.3. Phylogeny was performed for subtype assignation.

Background and objective:HIV-1 vertically infected children stand a high risk of HIV-1 drug resistance (HIVDR), especially after failure to prevention of mother to child transmission (PMTCT) and pediatric antiretroviral therapy (ART). Thus, surveillance of HIVDR might contribute in delineating optimal pediatric regimens. The objective of this study was to evaluate HIVDR and subtype distribution among ART-naïve and ART-failing children. Methods:A study was conducted throughout 2017 amongst 102 children/adolescents at the "Chantal BIYA International Reference Centre" (CIRCB) in Cameroon. HIVDR testing was performed in protease-reverse transcriptase (RT) region and interpreted using the Stanford HIVdbv8.5; subtyping was performed using MEGA v7.0.26; and data were analyzed using Epi-info v7.1.3.3, with p < 0.05 considered statistically significant.Results: Sequences were generated from 63 participants (19 ART-naïve, 44 ART-failure); the median-age was respectively 6 [IQR:3.5-11] and 144 [IQR:116.25-185] months for ART-naïve and ART-failing (median ARTduration: 23.55 [IQR:7.61-60.91] months, 63.6% receiving non-nucleoside RT inhibitors [NNRTI]-based regimens). Among ART-naïve children, overall-HIVDR was 52.6% (10/19), with 31.6% (6/19) to NNRTI, 26.3% (5/19) to nucleoside RT inhibitors (NRTI) and 15.8% (3/19) to ritonavir-boosted protease inhibitor (PI/r). Among ART-failing children, overall-HIVDR was 97.7% (43/44), with 95.4% (42/44) to NNRTI, 90.9% (40/44) to NRTI and 18.2% (8/44) to PI/r. Multi-drug resistance was found in 21.05% (4/19) ART-naïve versus 85.7%(24/28) on NNRTI-based and 50% (8/16) on PI-based regimens; OR = 4.36, p = 0.045. CRF02_AG was prevalent (68.2%), without any effect on HIVDR (p = 0.99). Conclusions:The high rates of HIVDR, in both ART-na-# These authors contributed equally to this work.Dambaya B. et al: HIV drug resistance and subtypes Explor Res Hypothesis Med ïve and ART-failing children, suggest using genotypic HIV-1 drug resistance testing for selecting optimal pediatric ART-regimens. Multi-drug resistance is concerning among children failing ART and prompts the need of new drugs (integrase inhibitors, darunavir/ritonavir) for optimal pediatric ART management.