Evaluation of archived drug resistance mutations in HIV‐1 DNA among vertically infected adolescents under antiretroviral treatment in Cameroon: Findings during the COVID‐19 pandemic

Abstract

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.

Evaluation of HIV-1 DNA levels among adolescents living with perinatally acquired HIV-1 in Yaounde, Cameroon: A contribution to paediatric HIV cure research in Sub-Saharan Africa

“… 2 These challenges include lifelong treatment exposure, adherence to ART, persistence of immune dysfunction and advent of drug resistance mutations (DRMs). 2 , 3 , 4 , 5 Moreover, despite the benefits of ART, it does not provide a sterilising HIV-1 cure due to the lifelong persistence of infection within sanctuaries. 6 Consequently, virological rebound post treatment cessation/interruption remains a concern largely attributed to the existence of reservoir cells, which constitute the main barrier to achieving HIV-1 functional cure or eradication.…”