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

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

doi:10.1371/journal.pone.0293326

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

PLoS One. 2023 Oct 25;18(10):e0293326. doi: 10.1371/journal.pone.0293326. eCollection 2023.

Authors

Willy Le Roi Togna Pabo^{1

2

3}, Joseph Fokam^{1

2

4

5}, Debimeh Njume^{1

2

4}, Désiré Takou¹, Maria-Mercedes Santoro⁶, Raymond Babila Nyasa³, Collins Chenwi^{1

2}, Marie Laure Mpouel^{1

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

6

7}, Alex Durand Nka^{1

6

7}, Aude Christelle Ka'e^{1

6}, Georges Teto¹, Beatrice Dambaya¹, Sandrine Djupsa¹, Davy Hyacinthe Gouissi Anguechia^{1

2}, Molimbou Evariste¹, Cedric Kamta⁸, Lionel Bala⁹, Virginie Lambo¹⁰, Edie Gregory Halle-Ekane⁴, Vittorio Colizzi^{1

6

7}, Carlo Federico Perno^{1

6

11}, Alexis Ndjolo^{1

2}, Roland Ndip Ndip³

Affiliations

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

Abstract

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.

Copyright: © 2023 Togna Pabo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Anti-HIV Agents* / pharmacology
Anti-HIV Agents* / therapeutic use
Cameroon / epidemiology
Cohort Studies
Drug Resistance, Viral / genetics
Female
HIV Infections* / drug therapy
HIV Seropositivity* / drug therapy
HIV-1*
Humans
Male
Viral Load

Substances

Anti-HIV Agents

Grants and funding

JF, TMA grant number:1027, awarded by the European and Developing Countries Clinical Trials Partnership (EDCTP), under the Career Development Fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.