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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 <250 cells/mm3), VF (viremia =1,000 copies/ml), and ADR were analyzed, with P<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<0.0001). From T1-T3 respectively, there were declining rates of IF (25.5, 18.9, and 9.83%, P<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. [ABSTRACT FROM AUTHOR]

Background: The elevated rate of AIDS-related mortality in Sub-Saharan Africa among adolescents living with HIV (ALHIV) is influenced by various factors, notably immunosuppression, within a framework of limited therapeutic alternatives. We aimed to enhance the management of pediatric HIV by assessing the immune response and associated factors in perinatally-infected ALHIV on antiretroviral therapy (ART) in Cameroon., Methods: A cohort study was conducted from 2018-2020 among 271 ART-experienced ALHIV in Cameroon. Sociodemographic data, immunological (CD4), and virological (plasma viral load, PVL) responses were measured at enrolment (T0), 6-months (T1), and 12-months (T2) using PIMA CD4 (Abbott/Pantech (Pty) Ltd) and Abbott Applied Biosystem platform (Real-Time PCR m2000RT) respectively. Immunological failure (IF) was defined as absolute CD4 < 250 cells/mm 3 , and Virological failure (VF) as PVL ≥ 1,000 copies/ml. A linear mixed-effects model with R version 4.4.1 was used to estimate both fixed and random effects, with significance set at p  < 0.05., Results: Of the 271 perinatally-infected ALHIV enrolled over three phases, females were predominant (55.7, 55.1, and 56.0%); median age was 14 (IQR: 12-17); majority of the participants were followed-up in urban areas (77.5, 74.5, and 78.6%); and the age distribution favored older adolescents (48.7, 61.2, and 58.5%). Most participants achieved clinical success (93.1, 89.7, 88.9%), predominantly on first-line ART (80.8, 66.2, and 53.0%), with good adherence (64.2, 58.9, and 64.5%). Most participants had secondary education (67.2, 70.1, and 67.5%). Median CD4+ counts fluctuated overtime, with values of 563 (IQR: 249.0-845.0), 502 (IQR: 319.0-783.5), and 628 (IQR: 427.5-817.5), respectively. Of note, being male was linked to a reduction in CD4+ count compared to females, [-200.63 (-379.32 to -21.95), p  = 0.028]. Similarly, late adolescence was associated with lower CD4+ counts compared to early adolescence, [-181.08 (-301.08 to -61.09), p  = 0.003]. Moreover, participants experiencing VF showed significantly lower CD4+ counts compared to those with undetectable viral loads, [-353.08 (-465.81 to -240.36), p  < 0.001]. Additionally, there was a marginally significant interaction between male gender and secondary educational level, [209.78 (-6.94-426.51), p  = 0.058]., Conclusion: Among perinatally-infected ALHIV, age, gender, educational level, and virological status are key factors influencing their immune health and treatment outcomes. Prioritizing targeted interventions and close monitoring within these subgroups is crucial for optimal management, employing holistic care strategies that consider not only medical interventions but also psychosocial support and education., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Togna Pabo, Kengni Ngueko, Nka, Santoro, Bouba, Chenwi, Ngoufack Jagni Semengue, Takou, Teto, Dambaya, Nyasa, Tommo Tchouaket, Beloumou, Djupsa Ndjeyep, Ka’e, Tekoh, Ayuk Ngwese, Etame, Mundo, Kamgaing, Sosso, Ndip, Colizzi, Cecchereni-Silberstein, Ndjolo and Fokam.)

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 3 ), 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&#95;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., (Copyright © 2023, the Author(s).)