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

Willy LE Roi Togna Pabo; Debimeh Njume; Roland Ndip Ndip; Désiré Takou; Maria-Mercedes Santoro; Collins Chenwi; Grace Beloumou; Ezechiel Ngoufack Jagni Semengue; Alex Durand Nka; Aude Christelle Ka'e; Georges Teto; Beatrice Dambaya; Sandrine Djupsa; Raymond Babila Nyasa; Davy Hyacinthe Gouissi Anguechia; Cedric Kamta; Lionel Bala; Virginie Lambo; Samuel Martin Sosso; Vittorio Colizzi; Carlo Federico Perno; Joseph Fokam; Alexis Ndjolo

doi:10.4081/jphia.2023.2612

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

J Public Health Afr. 2023 Oct 1;14(10):2612. doi: 10.4081/jphia.2023.2612. eCollection 2023 Oct 31.

Authors

Willy LE Roi Togna Pabo, Debimeh Njume^{1

2

3}, Roland Ndip Ndip⁴, Désiré Takou¹, Maria-Mercedes Santoro⁵, Collins Chenwi^{1

2}, Grace Beloumou¹, Ezechiel Ngoufack Jagni Semengue^{1

5

6}, Alex Durand Nka^{1

5

6}, Aude Christelle Ka'e^{1

5}, Georges Teto¹, Beatrice Dambaya¹, Sandrine Djupsa¹, Raymond Babila Nyasa⁴, Davy Hyacinthe Gouissi Anguechia^{1

2}, Cedric Kamta⁷, Lionel Bala⁸, Virginie Lambo⁹, Samuel Martin Sosso¹, Vittorio Colizzi^{1

5

6}, Carlo Federico Perno^{1

5

10}, Joseph Fokam^{1

2

3

11}, Alexis Ndjolo^{1

2}

Affiliations

¹ Chantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé.
² Faculty of Medicine and Biomedical Sciences, Yaoundé.
³ Faculty of Health Sciences, University of Buea, Buea, Cameroon.
⁴ Faculty of Science, University of Buea, Buea.
⁵ University of Rome Tor Vergata, Rome, Italy.
⁶ Evangelic University of Cameroon, Bandjoun.
⁷ Mfou District Hospital, Mfou.
⁸ Mbalmayo District Hospital, Mbalmayo.
⁹ Nkomo Integrated Health Center, Nkomo, Cameroon.
¹⁰ Bambino Gesu Pediatric Hospital, Rome, Italy.
¹¹ National HIV Drug Resistance Group, Ministry of Public Health, Yaoundé, Cameroon.

Abstract

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.

Keywords: Cameroon; HIV care; HIV drug resistance; adolescents; antiretroviral therapy; viral load.

Grants and funding

Funding: The study was financially supported by EDCTP, the European and Developing Countries Clinical Trials Partnership, under the Career Development Fellowship-TMA 1027.