BACKGROUND Adherence to daily oral pre-exposure prophylaxis (PrEP) is low among African young women, and layered support strategies are needed to improve PrEP adherence in this population. We aimed to evaluate potentially scalable adherence-support strategies for young women aged 18-25 years who initiated PrEP in Johannesburg, South Africa. METHODS We conducted a sequential multiple-assignment randomised trial at Ward 21 of the Wits Reproductive Health and HIV Institute clinical research site, affiliated with University of the Witwatersrand, Johannesburg, South Africa. Participants were eligible if they were assigned female sex at birth, aged 18-25 years, not living with HIV, sexually active, newly initiating PrEP, had regular access to a mobile telephone, and could read. Using sequentially numbered, sealed, opaque envelopes containing group allocation, a staff member assigned enrolled participants (1:1) to receive one of two adherence-support interventions: once per week two-way SMS communication or participation in a WhatsApp peer-support group. Participants assigned to WhatsApp were put into groups with approximately 25 participants, during which they were prompted by staff facilitators to discuss any challenges with PrEP use or other events happening in their lives. The allocation sequence was generated by the data manager using random numbers with variable block sizes between 10 and 14. Only trial investigators were masked to participant intervention assignments; participants, people giving interventions, people assessing outcomes, and people analysing data were not masked to group assignment. All enrolled participants were offered PrEP (ie, co-formulated, once per day oral emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg). The primary outcome was high PrEP adherence at month 9, defined as concentration of tenofovir diphosphate on dried blood sample of 700 fmol per punch or more. At month 3, participants with low PrEP adherence were randomly assigned to a secondary, intensified intervention of issue-focused counselling once per month or drug-level feedback counselling based on PrEP drug concentrations at months 3 and 6. The protocol was registered at ClinicalTrials.gov (NCT04038060) and the trial is complete. FINDINGS Participants were enrolled and followed up between May 16, 2019, and Jan 25, 2022. From May 16, 2019, to Jan 29, 2021, 401 participants were screened and 360 were enrolled and initiated PrEP. 180 (50%) were randomly assigned to two-way SMS and 180 (50%) were randomly assigned to WhatsApp support groups. At month 9, 34 (20%) of 174 participants in the two-way SMS arm had tenofovir diphosphate 700 fmol per punch or more, compared with 32 (18%) of 174 in the WhatsApp arm (relative risk 1·06, 95% CI 0·69-1·64; p=0·78). At month 9, four (5%) of 76 participants in the drug-level feedback arm had tenofovir diphosphate 700 fmol per punch or more, compared with three (4%) of 76 participants in the monthly counselling arm (1·33, 0·31-5·76; p=0·70). 22 serious adverse events were reported during the trial, but were all deemed unrelated to the trial. INTERPRETATION PrEP adherence did not differ across interventions among young women in Johannesburg, South Africa. Future research is needed on whether and how to scale-up PrEP support for young women in resource-constrained settings. FUNDING US National Institutes of Health.

中文翻译：

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南非约翰内斯堡年轻女性的适应性 HIV 暴露前预防依从性干预：一项序贯多分配随机试验。


背景 非洲年轻女性对每日口服暴露前预防 （PrEP） 的依从性较低，需要分层支持策略来提高该人群的 PrEP 依从性。我们旨在评估在南非约翰内斯堡开始 PrEP 的 18-25 岁年轻女性的潜在可扩展依从性支持策略。方法 我们在南非约翰内斯堡金山大学附属的金山生殖健康和 HIV 研究所临床研究站点的 21 病房进行了一项序贯多分配随机试验。如果参与者出生时被分配为女性、年龄在 18-25 岁之间、未感染 HIV、性活跃、新开始服用 PrEP、经常使用手机并且能够阅读，则他们符合条件。工作人员使用包含小组分配的按顺序编号、密封、不透明的信封，分配注册参与者 （1：1） 接受两种依从性支持干预措施之一：每周一次双向 SMS 通信或参加 WhatsApp 同伴支持小组。分配到 WhatsApp 的参与者被分成大约 25 名参与者的小组，在此期间，工作人员协调员会提示他们讨论使用 PrEP 或他们生活中发生的其他事件方面的任何挑战。分配序列由数据管理器使用随机数生成，可变块大小在 10 到 14 之间。只有试验调查人员对参与者干预任务不知情;受试者、进行干预的人、评估结局的人和分析数据的人没有被小组分配所蒙蔽。所有入组的参与者都接受了 PrEP（即共同配制，每天一次口服恩曲他滨 200 毫克和富马酸替诺福韦二吡呋酯 300 毫克）。 主要结局是第 9 个月时 PrEP 的高依从性，定义为干血样中替诺福韦二磷酸浓度为每针 700 fmol 或更高。在第 3 个月，PrEP 依从性低的参与者被随机分配到每月一次以问题为中心的辅助强化干预，或在第 3 个月和第 6 个月根据 PrEP 药物浓度进行药物水平的反馈咨询。该方案于 ClinicalTrials.gov （NCT04038060） 注册，试验已完成。结果 参与者在 2019 年 5 月 16 日至 2022 年 1 月 25 日期间入组并进行了随访。从 2019 年 5 月 16 日到 2021 年 1 月 29 日，筛选了 401 名参与者，招募了 360 名参与者并开始服用 PrEP。180 名 （50%） 被随机分配到双向短信组，180 名 （50%） 被随机分配到 WhatsApp 支持组。在第 9 个月时，双向 SMS 组的 174 名参与者中有 34 名 （20%） 的二磷酸替诺福韦每次打孔 700 fmol 或更高，而 WhatsApp 组的 174 名参与者中有 32 名 （18%） （相对风险 1·06,95% CI 0·69-1·64;p=0·78）。在第 9 个月时，药物水平反馈组的 76 名参与者中有 4 名 （5%） 的二磷酸替诺福韦每次打孔 700 fmol 或更高，而月度咨询组的 76 名参与者中有 3 名 （4%） （1·33， 0·31-5·76;p=0·70）。试验期间报告了 22 例严重不良事件，但均被认为与试验无关。解释 南非约翰内斯堡年轻女性的干预措施对 PrEP 的依从性没有差异。未来需要研究是否以及如何在资源受限的环境中扩大对年轻女性的 PrEP 支持。资助美国国立卫生研究院。