HIV-1 Drug Resistance and Genetic Diversity among Vertically Infected Cameroonian Children and Adolescents

Abstract

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.

Determinants of survival of adolescents receiving antiretroviral therapy in the Centre Region of Cameroon: a multi-centered cohort-analysis

“…To add, the same team in 2019 showed declining rates of virological success after 36 months of treatment on NNRTI regimes, driven by poor adherence and probably emergence of drug resistance mutations to NNRTI which have a low genetic barrier. In 2020, Dambaya et al described rates of 52.6% for overall drug resistance in treatment naïve patients (NNRTI resistance consisting 31.6%), with rates of NNRTI resistance as high as 90%, similar to findings by Fokam et al in 2021 [11,12]. Lastly, the majority of our adolescents were either single or double parent orphans, with most of them not knowing their status (non-disclosure).…”

“…This therefore calls for the effective implementation and scale up of better strategies such as community dispensation of ART and even HIV services (such as viral load testing) in rural areas, so as to fill this gap, while also mitigating the high patient-to-staff ratio (i.e. higher workload) and distances from healthcare centers in rural settings [12,22]. It is worth noting that, community dispensation of ART was initiated in Cameroon in 2016, but needs to be expanded from urban areas (where the large majority of patients and treatment centers are located) to rural settings, so as to improve the availability of ART in the rural setting [20].…”

“…These challenges are also associated with increased risks of virological failure and HIV drug resistance (HIVDR) emergence which is a threat to ART effectiveness in Sub-Saharan African health programs, including Cameroon [10,11]. Of note, the prevalence of baseline HIVDR in pediatric population in Cameroon is around 50%, essentially driven by mutations associated with non-nucleoside reverse-transcriptase inhibitors (NNRTI) [12]. Furthermore, Cameroonian adolescents receiving ART were found with 34.2% rate of virological failure and over 90% rate of HIVDR among those experiencing treatment failure in the Centre region of the country [11,12].…”

“…Of note, the prevalence of baseline HIVDR in pediatric population in Cameroon is around 50%, essentially driven by mutations associated with non-nucleoside reverse-transcriptase inhibitors (NNRTI) [12]. Furthermore, Cameroonian adolescents receiving ART were found with 34.2% rate of virological failure and over 90% rate of HIVDR among those experiencing treatment failure in the Centre region of the country [11,12]. Hence adolescents are now recognized as a distinct population, and have been described as the 'fulcrum' and the center of the epidemic' with different health requirements for children as compared to adults [9,13].…”