Programme quality indicators of HIV drug resistance among adolescents in urban versus rural settings of the centre region of Cameroon.

BACKGROUND: The high rate of mortality among HIV-vertically infected adolescents might be favoured by HIV drug resistance (HIVDR) emergence, which calls for timeous actions in this underserved population. We thus sought to evaluate program quality indicators (PQIs) of HIVDR among HIV-vertically infected adolescents on antiretroviral therapy (ART). METHODS: A study was conducted in the Centre region of Cameroon among adolescents (10-19 years) receiving ART in two urban (The Mother-Child Centre of the Chantal BIYA Foundation, the National Social Welfare Hospital) and three rural (Mfou District Hospital, Mbalmayo District Hospital and Nkomo Medical Center) health facilities. Following an exhaustive sampling from ART registers, patient medical files and pharmacy records, data was abstracted for seven PQIs: on-time drug pick-up; retention in care; pharmacy stock outs; dispensing practices; viral load coverage; viral suppression and adequate switch to second-line. Performance in PQIs was interpreted following the WHO-recommended thresholds (desirable, fair and/or poor); with p < 0.05 considered significant. RESULTS: Among 967 adolescents (888 urban versus 79 rural) registered in the study sites, validated data was available for 633 (554 in urban and 79 in rural). Performance in the urban vs. rural settings was respectively: on-time drug pick-up was significantly poorer in rural (79% vs. 46%, p = 0.00000006); retention in care was fair in urban (80% vs. 72%, p = 0.17); pharmacy stock outs was significantly higher in urban settings (92% vs. 50%, p = 0.004); dispensing practices was desirable (100% vs. 100%, p = 1.000); viral load coverage was desirable only in urban sites (84% vs. 37%, p < 0.0001); viral suppression was poor (33% vs. 53%, p = 0.08); adequate switch to second-line varied (38.1% vs. 100%, p = 0.384). CONCLUSION: Among adolescents on ART in Cameroon, dispensing practices are appropriate, while adherence to ART program and viral load coverage are better in urban settings. However, in both urban and rural settings, pharmacy stock outs, poor viral suppression and inadequate switch to second-line among adolescents require corrective public-health actions to limit HIVDR and to improve transition towards adult care in countries sharing similar programmatic features.

Genotypic resistance testing improves antiretroviral treatment outcomes in a cohort of adolescents in Cameroon: Implications in the dolutegravir-era.

Acquired drug resistance (ADR) is common among adolescents living with perinatal HIV (APHI) in sub-Saharan Africa (SSA). Personalized management has the potential to improve pediatric antiretroviral therapy (ART), even in the presence of long-term treatment and HIV-1 subtype diversity. We sought to evaluate the effect of HIV-1 mutational profiling on immuno-virological response and ADR among APHI. A cohort-study was conducted from 2018-2020 among 311 APHI receiving ART in Cameroon. Clinical, immunological and virological responses were measured at enrolment (T1), 6-months (T2) and 12-months (T3). Immunological failure (IF: CD4 #x003C;250 cells/mm3), VF (viremia ≥1,000 copies/ml), and ADR were analyzed, with P#x003C;0.05 considered significant. Mean age was 15(±3) years; male-female ratio was 1:1; median [IQR] ART-duration was 36[21-81] months. At T1, T2, and T3 respectively, adherence-level was 66.4, 58.3 and 66.5%; 14 viral clades were found, driven by CRF02_AG (58.6%); ADR-mutations favored increased switch to second-line ART (16.1, 31.2, and 41.9%, P#x003C;0.0001). From T1-T3 respectively, there were declining rates of IF (25.5, 18.9, and 9.83%, P#x003C;0.0001), VF (39.7, 39.9, and 28.2%, P=0.007), and HIVDR (96.4, 91.7, and 85.0%, P=0.099). Predictors of ADR were being on first-line ART (P=0.045), high viremia at enrolment (AOR=12.56, P=0.059), and IF (AOR=5.86, P=0.010). Of note, optimized ART guided by mutational profile (AOR=0.05, P=0.002) was protective. Moreover, full Tenofovir+Lamivudine+Dolutegravir efficacy was predicted in 77 and 62% of APHI respectively after first- and second-line failure. Among APHI in this SSA setting, viral mutational profiling prompts the use of optimized Dolutegravir-based ART regimens, leading to improved immuno-virological response and declining ADR burdens. Thus, implementing personalized HIV medicine in this vulnerable population would substantially improve ART response and the achievement of the 95-95-95 goals in these underserved populations.

HIV-1 subtype diversity and immuno-virological outcomes among adolescents failing antiretroviral therapy in Cameroon: A cohort study.

OBJECTIVE: We sought to evaluate the variability of HIV-1 and its effect on immuno-virological response among adolescents living with perinatally acquired HIV (APHI). METHODS: A cohort study was conducted from 2018-2020 among 311 APHI receiving antiretroviral therapy (ART) in Cameroon. Sequencing of protease and reverse transcriptase regions was performed for participants experiencing virological failure, VF, (Plasma viral load, PVL ≥ 1000 RNA copies/ml). HIV-1 subtypes were inferred by phylogeny; immuno-virological responses were monitored at 3-time points (T1-T3). Cox regression modeling was used to estimate adjusted hazard ratios (aHRs) of progression to: CD4 < 250, and PVL > 5log10, adjusted for acquired drug resistance, gender, ART line, adherence, and duration on treatment; p < 0.05 was considered statistically significant. RESULTS: Of the 141 participants in VF enrolled, the male-female ratio was 1:1; mean age was 15 (±3) years; and median [IQR] duration on ART was 51 [46-60] months. In all phases, 17 viral clades were found with a predominant CRF02_AG (58.2%, 59.4%, and 58.3%). From T1-T3 respectively, there was an increasing CD4 count (213 [154-313], 366 [309-469], and 438 [364-569] cells/mm3) and decline log10 PVL (5.23, 4.43, and 4.43), similar across subtypes. Among participants with CRF02_AG infection, duration of treatment was significantly associated with both rates of progression to CD4 < 250, and PVL > 5log10, aHR = 0.02 (0.001-0.52), and aHR = 0.05 (0.01-0.47) respectively. Moreover, four potential new HIV-1 recombinants were identified (CRF02_AG/02D, CRF02_AG/02A1F2, D/CRF02_AG, and AF2/CRF02_AG), indicating a wide viral diversity. CONCLUSION: Among APHI in settings like Cameroon, there is a wide genetic diversity of HIV-1, driven by CRF02_AG and with potential novel clades due to ongoing recombination events. Duration of treatment significantly reduces the risk of disease progression.