Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA; Department of Global Health, University of Washington, Seattle, WA, USA.
Department of Global Health, University of Washington, Seattle, WA, USA; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Lancet HIV. 2022 Oct;9(10):e680-e689. doi: 10.1016/S2352-3018(22)00195-3. Epub 2022 Sep 7.
Adolescent girls and young women in southern and eastern Africa have adherence challenges with daily oral HIV pre-exposure prophylaxis (PrEP). High adherence is most important during periods of HIV risk (prevention-effective adherence). We aimed to describe HIV risk behaviour and to understand patterns in PrEP adherence during periods of risk among adolescent girls and young women from sub-Saharan Africa.
We did a secondary analysis of the HPTN 082 trial, an open-label, interventional, randomised controlled trial of sexually active adolescent girls and young women (aged 16-25 years) testing negative for HIV in Johannesburg and Cape Town, South Africa, and in Harare, Zimbabwe. The primary outcomes were high cumulative PrEP adherence, dichotomised as intracellular tenofovir diphosphate concentrations of at least 700 fmol/punch in dried blood spots at weeks 13, 26, and 52, and high recent PrEP adherence, dichotomised as plasma tenofovir concentrations of at least 40 ng/mL at weeks 13, 26, and 52, among participants who accepted PrEP. We collected data on sexual behaviour every 3 months. We categorised visits into a binary variable of any HIV risk based on condomless sex, more than one sexual partner, primary partner's HIV status and antiretroviral use, transactional sex, drug or alcohol use around sexual activity, and laboratory-diagnosed STIs. We used generalised estimating equations to evaluate associations between HIV risk (reflecting behaviour during the previous 3 months) and high cumulative and recent adherence to PrEP and any PrEP use (quantifiable drug concentrations). The trial is registered with ClinicalTrials.gov, NCT02732730.
Between Oct 12, 2016, and Oct 25, 2018, 451 women were recruited, and 427 participants (median age 21·0 years [IQR 19·0-22·0]) were eligible for inclusion in this analysis. The proportion of participants reporting at least one HIV risk factor decreased significantly over follow-up, from 364 (85%) participants at enrolment, 226 (60%) at week 13, and 243 (65%) at week 26, to 224 (61%) at week 52 (p<0·0001). Any HIV risk was significantly associated with high PrEP adherence, measured by both tenofovir diphosphate concentrations of at least 700 fmol/punch (adjusted relative risk 1·57 [95% CI 1·09-2·25]; p=0·014) and plasma tenofovir concentrations of at least 40 ng/mL (1·36 [1·11-1·65]; p=0·0025). Any HIV risk was also associated with quantifiable concentrations of tenofovir diphosphate (1·15 [1·03-1·29]; p=0·013) and tenofovir (1·27 [1·09-1·49]; p=0·0022). We observed significant dose-response relationships between number of HIV risk factors and PrEP drug concentrations.
The association between any HIV risk and high PrEP adherence suggests that adolescent girls and young women were able to use PrEP during periods of risk, an indicator of prevention-effective PrEP adherence. Our findings support a shift in the PrEP framework to acknowledge prevention-effective adherence practices, which might improve PrEP delivery and adherence support for adolescent girls and young women in HIV-endemic settings.
US National Institutes of Health.
在南部和东部非洲，青少年女孩和年轻女性在日常口服 HIV 暴露前预防（PrEP）方面存在依从性挑战。在 HIV 风险期（预防有效依从性）期间，最重要的是保持高依从性。我们旨在描述 HIV 风险行为，并了解撒哈拉以南非洲青少年女孩和年轻女性在风险期内 PrEP 依从性的模式。
我们对 HPTN 082 试验进行了二次分析，这是一项在南非约翰内斯堡和开普敦以及津巴布韦哈拉雷对 HIV 检测阴性的活跃青少年女孩和年轻女性（年龄 16-25 岁）进行的开放性、干预性、随机对照试验。主要结果是高累积 PrEP 依从性，用周 13、26 和 52 时的细胞内替诺福韦二磷酸浓度至少为 700fmol/打孔来衡量，以及高近期 PrEP 依从性，用周 13、26 和 52 时的血浆替诺福韦浓度至少为 40ng/mL 来衡量，在接受 PrEP 的参与者中。我们每 3 个月收集一次性行为数据。我们根据无保护性行为、多于一个性伴侣、主要性伴侣的 HIV 状况和抗逆转录病毒使用、交易性性行为、性行为周围的药物或酒精使用以及实验室诊断的性传播感染，将就诊分为二项变量的任何 HIV 风险。我们使用广义估计方程评估 HIV 风险（反映前 3 个月的行为）与高累积和近期 PrEP 依从性以及任何 PrEP 使用（可量化的药物浓度）之间的关联。该试验在 ClinicalTrials.gov 注册，NCT02732730。
在 2016 年 10 月 12 日至 2018 年 10 月 25 日期间，共招募了 451 名女性，427 名参与者（中位年龄 21.0 岁[IQR 19.0-22.0]）符合纳入本分析的条件。随着随访的进行，报告至少有一个 HIV 风险因素的参与者比例显著下降，从纳入时的 364 名（85%）参与者、第 13 周的 226 名（60%）和第 26 周的 243 名（65%）降至第 52 周的 224 名（61%）（p<0.0001）。任何 HIV 风险均与高 PrEP 依从性显著相关，这是通过检测周 13、26 和 52 时细胞内替诺福韦二磷酸浓度至少为 700fmol/打孔（调整后的相对风险 1.57[95%CI 1.09-2.25]；p=0.014）和血浆替诺福韦浓度至少为 40ng/mL（1.36[1.11-1.65]；p=0.0025）来衡量的。任何 HIV 风险也与替诺福韦二磷酸（1.15[1.03-1.29]；p=0.013）和替诺福韦（1.27[1.09-1.49]；p=0.0022）的可量化浓度相关。我们观察到 HIV 风险因素数量与 PrEP 药物浓度之间存在显著的剂量-反应关系。
任何 HIV 风险与高 PrEP 依从性之间的关联表明，青少年女孩和年轻女性在风险期内能够使用 PrEP，这是预防有效 PrEP 依从性的一个指标。我们的研究结果支持将 PrEP 框架转变为承认预防有效依从性实践，这可能会改善 HIV 流行地区青少年女孩和年轻女性的 PrEP 提供和依从性支持。
美国国立卫生研究院。
