Chantal Biya International Reference Centre (CIRCB), Yaounde, Cameroon.
PhD Courses in Microbiology, Immunology, Infectious Diseases and Transplants (MIMIT), University of Rome "Tor Vergata", Rome, Italy.
HIV Med. 2023 Jun;24(6):691-702. doi: 10.1111/hiv.13459. Epub 2023 Jan 30.
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.
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 log HIV-1 RNA copies/ml) and non-viraemic (< 1.60 log copies/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.
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.
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.
随着抗逆转录病毒疗法（ART）的成功，越来越多感染 HIV 的儿童能够进入青春期。然而，青少年 HIV 感染者（ALHIV）经常不遵医嘱进行 ART，导致病毒复制。值得注意的是，病毒血症感染可能导致已储存的耐药突变（ADRM）。因此，在 COVID-19 大流行的背景下，我们旨在比较病毒血症和非病毒血症垂直感染的 ALHIV 中 ADRM 的模式，并评估他们对 SARS-CoV-2 的免疫和诊断。
2021 年 10 月至 2022 年 3 月期间，在喀麦隆雅温得对接受 ART 治疗的未接种 COVID-19 的 ALHIV 进行了一项比较研究。使用 Abbott® m2000rt 测量血浆 HIV-RNA；在 buffy-coat（HIV-1 DNA）上进行 HIV-1 基因分型，并使用 HIVdb.v9.0.1 解释 ADRM。比较病毒血症（≥1.60 log HIV-1 RNA 拷贝/ml）和非病毒血症（<1.60 log 拷贝/ml）个体中 HIV-1 ADRM 的模式。使用 Abbott Panbio COVID-19 免疫球蛋白 G/M（IgG/IgM）快速检测试剂盒检测全血中的 SARS-CoV-2 抗体，并使用鼻咽拭子样本进行 COVID-19 聚合酶链反应检测。
60 名 ALHIV[年龄 17（16-19）岁，51.6%为女性]，中位 ART 持续时间为 14（12-16）年；31/55（56.3%）接受过基于非核苷类逆转录酶抑制剂（NNRTI）的一线 ART（其中 19/31 于 2020 年转为多替拉韦为基础的 ART），24/55（43.6%）接受二线 ART。60 名 ALHIV 中有 42 名（70.0%）为非病毒血症；60 名中有 43 名（71.6%）成功测序。总体上，ADRM 发生率为 62.7%（27/43），病毒血症组为 69.2%（9/13），非病毒血症组为 60.0%（18/30）（p=0.56）。病毒血症 ALHIV 中 NNRTI-ADRM 显著更高[69.2%比 46.7%，p=0.030]。关于免疫，CD4 细胞计数最低点 <350 个/μl 的患者 ADRM 发生率显著更高[调整后的优势比（aOR）=3.20（1.36-95.53），p=0.03]。关于 COVID-19 免疫，总体 SARS-CoV-2 IgG 血清阳性率为 28.3%（17/60），而 IgM 血清阳性率为 0%（0/60）；特别是 CD4 细胞计数最低点 ≥350 个/μl 的患者 SARS-CoV-2 IgG 血清阳性率更高[OR=7.85（2.03-30.28），p<0.01]。SARS-CoV-2 IgG 血清阳性与 HIV-RNA 之间无显著相关性（非病毒血症，33.3%；病毒血症，16.7%；p=0.18）。SARS-CoV-2 RNA 流行率为 4.5%（2/44）。这两个阳性参与者的病毒载量水平较低（Ct>30），且 IgG 血清阳性。
在病毒学成功的情况下，大多数 ALHIV 携带 ADRM，主要由 NNRTI 突变和低 CD4 细胞计数最低点驱动。在当前大流行期间，约三分之一的 ALHIV 以前曾接触过 SARS-CoV-2。然而，一些儿童可能已经接触过但未感染，而另一些儿童可能已经感染但在采样时没有出现血清学反应。这些发现支持在这种大流行期间对 ALHIV 使用 NNRTI 节约方案和实施针对 COVID-19 的屏障措施。
