HIV-1 subtype diversity and immuno-virological outcomes among adolescents failing antiretroviral therapy in Cameroon: A cohort study.
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Togna Pabo Willy Le Roi, Fokam Joseph, Njume Debimeh, Takou Désiré, Santoro Maria-Mercedes, Nyasa Raymond Babila, Chenwi Collins, Mpouel Marie Laure, Beloumou Grace, Jagni Ezechiel Semengue Ngoufack, Nka Alex Durand, Ka'e Aude Christelle, Teto Georges, Dambaya Beatrice, Djupsa Sandrine, Gouissi Anguechia Davy Hyacinthe, Evariste Molimbou, Kamta Cedric, Bala Lionel, Lambo Virginie, Halle-Ekane Edie Gregory, Colizzi Vittorio, Perno Carlo Federico, Ndjolo Alexis, Ndip Ndip Roland
Аннотация
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.