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PA-402 Predictors of archived HIV-1 drug resistance mutations in cellular reservoirs of virally suppressed adolescents: the EDCTP READY-study TMA2025-CDF1027
Ist Teil von
BMJ global health, 2023-12, Vol.8 (Suppl 10), p.A77-A77
Ort / Verlag
London: BMJ Publishing Group Ltd
Erscheinungsjahr
2023
Quelle
EZB Electronic Journals Library
Beschreibungen/Notizen
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.