Pabo Willy LE Roi Togna, Njume Debimeh, Ndip Roland Ndip, Takou Désiré, Santoro Maria-Mercedes, Chenwi Collins, Beloumou Grace, Semengue Ezechiel Ngoufack Jagni, Nka Alex Durand, Ka'e Aude Christelle, Teto Georges, Dambaya Beatrice, Djupsa Sandrine, Nyasa Raymond Babila, Anguechia Davy Hyacinthe Gouissi, Kamta Cedric, Bala Lionel, Lambo Virginie, Sosso Samuel Martin, Colizzi Vittorio, Perno Carlo Federico, Fokam Joseph, Ndjolo Alexis
Chantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé.
Faculty of Medicine and Biomedical Sciences, Yaoundé.
J Public Health Afr. 2023 Oct 1;14(10):2612. doi: 10.4081/jphia.2023.2612. eCollection 2023 Oct 31.
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/mm), 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.
获得性耐药（ADR）在撒哈拉以南非洲（SSA）感染围产期HIV的青少年（APHI）中很常见。即使存在长期治疗和HIV-1亚型多样性，个性化管理仍有可能改善儿科抗逆转录病毒疗法（ART）。我们试图评估HIV-1突变谱分析对APHI免疫病毒学反应和ADR的影响。2018年至2020年在喀麦隆对311名接受ART的APHI进行了一项队列研究。在入组时（T1）、6个月时（T2）和12个月时（T3）测量临床、免疫和病毒学反应。分析免疫失败（IF：CD4＜250个细胞/mm³）、病毒血症（VF：病毒血症≥1000拷贝/ml）和ADR，P＜0.05被认为具有统计学意义。平均年龄为15（±3）岁；男女比例为1:1；ART疗程中位数[四分位间距]为36[21-81]个月。在T1、T2和T3时，依从性水平分别为66.4%、58.3%和66.5%；发现了14种病毒分支，以CRF02_AG为主导（58.6%）；ADR突变有利于增加二线ART的转换率（16.1%、31.2%和41.9%，P＜0.0001）。从T1到T3，IF发生率分别下降（25.5%、18.9%和9.83%，P＜0.0001）、VF发生率分别下降（39.7%、39.9%和28.2%，P=0.007）以及HIVDR发生率分别下降（96.4%、91.7%和85.0%，P=0.099）。ADR的预测因素包括接受一线ART（P=0.045）、入组时高病毒血症（调整后比值比[AOR]=12.56，P=0.059）和IF（AOR=5.86，P=0.010）。值得注意的是，由突变谱指导的优化ART（AOR=0.05，P=0.002）具有保护作用。此外，在一线和二线治疗失败后，分别有77%和62%的APHI预测Tenofovir+Lamivudine+Dolutegravir全效。在这个SSA地区的APHI中，病毒突变谱分析促使使用基于Dolutegravir的优化ART方案，从而改善免疫病毒学反应并降低ADR负担。因此，在这个弱势群体中实施个性化HIV药物治疗将大幅改善ART反应，并在这些服务不足的人群中实现95-95-95目标。
