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Objective: We sought to evaluate the variability of HIV-1 and its effect on immuno-virological response among adolescents living with perinatally acquired HIV (APHI). 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. [ABSTRACT FROM AUTHOR]

Background: With the success of antiretroviral therapy (ART), children born with HIV are more likely to reach adolescence. However, frequent non‐adherence to ART in adolescents living with HIV (ALHIV) leads to viral replication. Notably, a viraemic infection might lead to archived drug resistance mutations (ADRMs). Hence, within the context of the COVID‐19 pandemic, we aimed to compare the patterns of ADRMs in viraemic and non‐viraemic vertically infected ALHIV and to assess their immunity to and diagnosis of SARS‐CoV‐2. Methods: A comparative study was conducted among COVID‐19‐unvaccinated ALHIV receiving ART in Yaoundé‐Cameroon over the period October 2021 to March 2022. Plasma HIV‐RNA was measured using Abbott® m2000rt; HIV‐1 genotyping was performed on buffy‐coat (HIV‐1 DNA) and ADRMs were interpreted using HIVdb.v9.0.1. Patterns of HIV‐1 ADRMs were compared between viraemic (≥ 1.60 log10HIV‐1 RNA copies/ml) and non‐viraemic (< 1.60 log10copies/ml) individuals. SARS‐CoV‐2 antibodies were assessed on whole blood using Abbott Panbio COVID‐19 immunoglobulin G/M (IgG/IgM) rapid test and COVID‐19 polymerase chain reaction test was performed using nasopharyngeal swab samples. Results: Of the 60 ALHIV [aged 17 (16–19) years, 51.6% female], median ART duration was 14 (12–16) years; 31/55 (56.3%) were exposed to nonnucleoside reverse transcriptase inhibitor (NNRTI)‐based first‐line ART (of whom 19/31 transitioned to dolutegravir‐based ART in 2020) and 24/55 (43.6%) were on second‐line ART. Forty‐two out of 60 (70.0%) ALHIV were non‐viraemic; 43/60 (71.6%) were successfully sequenced. Overall the ADRM rate was 62.7% (27/43), with 69.2% (9/13) viraemic and 60.0% (18/30) non‐viraemic (p = 0.56). NNRTI‐ADRMs were significantly higher among viraemic ALHIV (69.2% vs. 46.7%, p = 0.030). Regarding immunity, those with CD4 nadir < 350 cells/μl had significantly higher rates of ADRMs [adjusted odds ratio (aOR) = 3.20 (1.36–95.53), p = 0.03]. In relation to COVID‐19 immunity, overall SARS‐CoV‐2 IgG seropositivity was 28.3% (17/60), whereas 0% (0/60) were seropositive to IgM; in particular, those with CD4 count nadir ≥ 350 cells/μl had higher odds of SARS‐CoV‐2 IgG seropositivity [OR =7.85 (2.03–30.28), p < 0.01]. No significant association was found between SARS‐CoV‐2 IgG seropositivity and HIV‐RNA (non‐viraemic, 33.3%; viraemic, 16.7%; p = 0.18). SARS‐CoV‐2 RNA prevalence was 4.5% (2/44). The two positive participants were with low‐levels of viral load (Ct > 30) and seropositive to IgG. Conclusion: In the context of virological success, the majority of ALHIV harbour ADRMs, essentially driven by NNRTI mutations and low CD4 nadir. During the current pandemic, about one‐third of ALHIV were previously exposed to SARS‐CoV‐2. However, some children might have been exposed and uninfected and others might have been infected but showed no serological response at sampling. These findings support the use of NNRTI‐sparing regimens and the implementation of COVID‐19 barrier measures targeting ALHIV during such a pandemic. [ABSTRACT FROM AUTHOR]