PA-402 Predictors of archived HIV-1 drug resistance mutations in cellular reservoirs of virally suppressed adolescents: the EDCTP READY-study TMA2025-CDF1027

BackgroundEven though 92% of people receiving antiretroviral treatment (ART) have achieved viral suppression (VS) globally, adolescents with perinatal HIV-infection (APHI) have challenges in sustaining VS, probably due to HIV-1 archived drug resistance mutations (ADRMs). Our objective was to investi...

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Published in:	BMJ global health Vol. 8; no. Suppl 10; p. A77
Main Authors:	Fokam, Joseph, Mpouel Bala Yanga, Marie Laure, Santoro, Maria-Mercedes, Takou, Désiré, Tala, Valère, Beloumou, Grace, Ngoufack, Ezechiel Semengue, Chenwi, Collins, Togna Pabo, Willy Leroy, Njume, Debimeh, Teto, Georges, Dambaya, Béatrice, Djupsa, Sandrine, Sosso, Samuel, Ateba, Francis, Kamta, Cedric, Bala, Lionel, Njom Nlend, Anne Esther, Ndombo, Paul Koki, Colizzi, Vittorio, Perno, Carlo Frederico, Ndjolo, Alexis
Format:	Journal Article
Language:	English
Published:	London BMJ Publishing Group Ltd 17-12-2023 BMJ Publishing Group LTD
Subjects:	Abstracts of Poster and e-Poster Presentations Drug resistance HIV Human immunodeficiency virus Mutation Teenagers Cameroon
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Summary:	BackgroundEven though 92% of people receiving antiretroviral treatment (ART) have achieved viral suppression (VS) globally, adolescents with perinatal HIV-infection (APHI) have challenges in sustaining VS, probably due to HIV-1 archived drug resistance mutations (ADRMs). Our objective was to investigate on ADRMs among APHI on VS in Cameroon.MethodsAn analytical study was conducted in 2021 among 38 consenting APHI on VS at the Chantal BIYA International Reference Centre (CIRCB) in Yaoundé-Cameroon. Proviral-HIV-1 DNA was extracted from buffy coat, DNA extracts were amplified, purified and sequenced by capillary electrophoresis. Generated proviral sequences were used to analyse ADRMs on HIVdb.v9.0. Molecular phylogeny was performed with MEGA v10x and data were analysed with a significance threshold of 5%.ResultsA total of 30 samples were successfully amplified, of which 28 sequences were obtained and one sequence was excluded due to APOBEC3G mutations. Sex ratio M/F was 3/4; median age was 14 years [IQR: 13–16.5]. Regarding ART, twelve (42.9%) were on first line, and the most common regimens were TDF+3TC+EFV and TDF+3TC+ATV/r; and 64.3% (18/28) were fully adherent. Regarding ART response, 92.9% were at WHO clinical stages 1/2; median CD4 was 642 [IQR: 421–769] cells/mm3; 32.1% (09/28) had undetectable viraemia. The prevalence of ADRMs was 59.2% (16/27), of which main DRMs by class were M184MV/I (25%), T215Y/IL/FS (15.9%) for nucleoside reverse transcriptase inhibitors (NRTIs); K103K/N (25.7%), A98A/G (14.3%) for non-NRTIs; I54V and V82VA (3.7% each) for PI/r. Second line of ART were associated with ADRMs (p=0.001). ADRMs were found in detectable (66.6% i.e. 12/18) versus undetectable viraemia (44.4% i.e. 04/09), p=0.58. Seven HIV-1clades were found, with CRF02_AG being prevalent (67.8%). ConclusionDespite VS, APHI harbour ADRMs, which underscore high risks of subsequent ART failure, even with undetectable viraemia. Limiting emerging ADRMs suggest targeting APHI on second-line ART, after previous exposure to NRTI-containing regimens.
Bibliography:	Abstracts of The Eleventh EDCTP Forum, 7–10 November 2023
ISSN:	2059-7908
DOI:	10.1136/bmjgh-2023-EDC.188