Department of Psychiatry, Michigan State University, East Lansing, MI 48824, USA.
Directorate of Public Health and Environment, Kampala Capital City Authority, Kampala 00256, Uganda.
Int J Environ Res Public Health. 2022 Mar 21;19(6):3725. doi: 10.3390/ijerph19063725.
(1) We examined the hypothesis that in utero/peripartum antiretroviral (IPA) exposure may affect the likelihood of developmental disorders-i.e., attention deficit and hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and functional impairment (FI). (2) Children and their primary caregivers were enrolled and followed for 12 months. The sample included 250 children perinatally HIV-infected (CPHIV), 250 children HIV-exposed and uninfected (CHEU) of women living with HIV, and 250 children HIV unexposed and uninfected (CHUU) at 6-18 years of age. CHEU's IPA exposure -type was established via medical records and categorized as no IPA, single-dose nevirapine with/without zidovudine (SdNVP ± AZT), SdNVP + AZT + Lamivudine (3TC), or combination ART (cART). Developmental disorders were assessed at months 0, 6, and 12 per caregiver response to standardized questions from the third edition of . Multivariable repeated measures linear regression models estimated standardized mean differences (SMDs) with 95% confidence intervals (95% CI) according to the IPA exposure type relative to CHUU with adjustment for the dyad's sociodemographic and psychosocial factors. (3) Relative to the CHUU, outcomes were similar for CPHIV/CHEU with cART, SdNVP ± AZT, and no anti-retroviral drug exposure in the peripartum period. For CHEU relative to CHUU, SdNVP + AZT + 3TC exposure was associated with lower resiliency (SMD = -0.26, 95% CI: -0.49, -0.51), and elevated scores on ADHD (SMD = 0.41, 95% CI: 0.12, 0.70), ASD (SMD = 0.40, 95% CI: 0.19, 0.61), and EBD (SMD = 0.32, 95% CI: 0.08, 0.56) probability and functional impairment (SMD = 0.39, 95% CI: 0.18, 0.61) index scores. With the exception of ADHD, the adverse association between SdNVP + AZT + 3TC and outcomes were replicated for CPHIV vs. CHUU. (4) The results provided reassuring evidence that cART exposure in the peripartum period is unlikely to be adversely associated with developmental disorder probability scores in late childhood and adolescent years. However, the peripartum SdNVP + AZT + 3TC exposure associated elevation in developmental disorder probability and functional limitation at 6-18 years of life is a concern.
（1）我们检验了这样一个假设，即在子宫内/围产期使用抗逆转录病毒药物（IPA）可能会影响发育障碍的可能性，即注意力缺陷多动障碍（ADHD）、自闭症谱系障碍（ASD）和功能障碍（FI）。（2）招募了儿童及其主要照顾者，并对他们进行了 12 个月的随访。该样本包括 250 名围产期 HIV 感染（CPHIV）儿童、250 名 HIV 暴露但未感染（CHEU）的 HIV 阳性妇女的儿童和 250 名未暴露于 HIV 的儿童（CHUU），年龄在 6-18 岁之间。CHEU 的 IPA 暴露类型是通过病历确定的，并分为无 IPA、单剂量奈韦拉平加/不加齐多夫定（SdNVP±AZT）、SdNVP+AZT+拉米夫定（3TC）或联合抗逆转录病毒治疗（cART）。根据照顾者对第三版标准问题的回答，在 0、6 和 12 个月时评估发育障碍。多变量重复测量线性回归模型根据 IPA 暴露类型相对于 CHUU 估计了标准化平均差异（SMD），并根据双胞胎的社会人口统计学和心理社会因素进行了调整。（3）与 CHUU 相比，CPHIV/CHEU 使用 cART、SdNVP±AZT 和围产期无抗逆转录病毒药物暴露的结果相似。与 CHUU 相比，CHEU 中 SdNVP+AZT+3TC 暴露与复原力较低（SMD=-0.26，95%CI：-0.49，-0.51）、ADHD（SMD=0.41，95%CI：0.12，0.70）、ASD（SMD=0.40，95%CI：0.19，0.61）和 EBD（SMD=0.32，95%CI：0.08，0.56）概率以及功能障碍（SMD=0.39，95%CI：0.18，0.61）指数评分较高有关。除了 ADHD 之外，CPHIV 与 CHUU 相比，SdNVP+AZT+3TC 与结果之间的不良关联也得到了复制。（4）研究结果提供了令人放心的证据，表明围产期 cART 暴露不太可能与儿童晚期和青少年时期的发育障碍概率评分不良相关。然而，围产期 SdNVP+AZT+3TC 暴露与 6-18 岁儿童发育障碍和功能障碍概率的升高有关，这令人担忧。
