Long-acting HIV Pre-Exposure Prophylaxis Integrated With Community-based Sexual and Reproductive Health in South Africa (LAPIS): A Hybrid (1a) Cluster Randomised Controlled Phase 3B Trial of Effectiveness and Implementation
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 2,052
- 试验地点
- 1
- 主要终点
- Uptake PrEP
研究概览
简要总结
The goal of this hybrid (1a) Cluster Randomised Controlled Trial phase 3B trial is to evaluate the effectiveness and implementation of offering a choice of HIV Pre-Exposure Products (PrEP) through community-based sexual and reproductive health services, on PrEP uptake and retention, and population prevalence of sexually transmissible HIV amongst adolescents and young adults living in rural South Africa.
Researchers will compare adding the choice of long-acting PrEP, i.e. two monthly injectable cabotegravir (CAB LA) or dapiravine vaginal ring and HIV post exposure prophylaxis packs to daily oral PrEP integrated with community-based SRH in the 20 intervention clusters with standard of care (SoC), daily oral PrEP integrated with community-based SRH in the 20 control clusters, on uptake and retention on PrEP. We hypothesise that offering a choice of long-acting or oral PrEP and PEP within the community-based delivery of SRH services will overcome the challenges and barriers to effective use of oral daily PrEP and lead to a population-level effect on uptake and retention on PrEP and thus the prevalence of sexually transmissible HIV amongst 15-30 year olds living in rural KwaZulu-Natal, South Africa.
详细描述
This is a pragmatic trial of adding in a choice of South African Health Products Registration Authority (SAHPRA) approved newer PrEP products - APRETUDE (cabotegravir) 600 mg\3 mL: DAPIRING (Dapivirine) 25mg Vaginal Ring:56/20.2.8/0979 (22/11/2022) - to the current national department of health approved oral daily PrEP with TVF/FTC (Tenofovir disoproxil/emtricitabine), Objective 1. To measure the effectiveness of the choice of oral and long-acting PrEP, including injectable (CAB LA) and vaginal ring (DapiRing), and post exposure prophylaxis (PEP) on increasing effective uptake (adoption), retention, and adherence of PrEP compared to oral PrEP in young people aged 15-30 in rural South Africa and to estimate the preliminary effect on transmissible HIV and HIV incidence.
Objective 2. To understand real-world implementation:
2.1 To explore the acceptability, appropriateness, preference, and reach of CABLA from the perspective of young people aged 15-30 and their communities in rural South Africa 2.2 To understand the feasibility, affordability, and scalability of delivering CABLA through community-based PrEP with SRH.
2.3 To identify implementation challenges and practical solutions for CABLA initiation, laboratory monitoring (e.g. RNA testing), and safe stopping within nurse-led and rural community-based clinical settings 2.4 To evaluate the safety and tolerability of CABLA compared to oral PrEP
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Investigator, Outcomes Assessor)
盲法说明
The statistician and clinical team will not participate in the public randomisation. The statistician will remain blinded until the analysis plan has been finalised and the database is locked. Investigators remain blinded to allocation throughout. The participants and intervention delivery teams are not blinded
入排标准
- 年龄范围
- 15 Years 至 30 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •All young men and women aged 15-30 who are residing in the 40 administrative clusters in the study district and attend any integrated SRH/HIV service
- •Documented HIV negative test
- •Suitable for PrEP and/or already on PrEP
- •Weight > 35 kg
- •Understand the required dosing schedule and HIV testing.
- •Aware that details can be shared with a peer navigator to support their follow-up
- •If pregnant or breast feeding and/or planning to become pregnant participant can be offered CAB LA, if risk of acquiring HIV out weighs unknown risk of CAB LA, but must understand that safety in pregnancy or breast feeding for CAB LA has not been established and oral daily PrEP is a safe alternative.
排除标准
- •History or presence of allergy to the study drugs or their components
- •Investigator assessment find them not suitable
- •Additional exclusion criteria for specific products:
- •CAB LA: Taking medication that is contraindicated (Carbamazepine, oxcarbazepine, phenobarbital, phenytoin, Rifampin, rifapentine) and Severe mental health disorder, Hep B surface antigen positive, living with hepatitis C and not yet treated, or abnormal liver function tests (ALT more than two times the upper limit of normal)
- •DapiRing: Pregnancy.
研究组 & 干预措施
Intervention: Choice of long-acting PrEP and PEP added to Thetha Nami ngithethe nawe
Tailored peer-led psychosocial support and social mobilisation into community based SRH and differentiated HIV care and prevention, including a choice of effective PrEP or PEP.
At the mobile AYFS in the intervention clusters nurses will offer the choice of either daily oral tenofovir/emtricitabine or injectable long acting cabotegravir (CAB LA) to be delivered to adolescents and young adults at risk of HIV acquisition. Those who decline will have the option of three monthly dapivarine vaginal rings or Post Exposure Prophylaxis (PEP) packs (tenofovir/lamuvidine/dolutegravir) to take home.
Peer navigators will promote long-acting PrEP in addition to oral PrEP. As part of the peer mentorship package, the peer naviators will remind young people of their follow-up visits.
干预措施: APRETUDE (cabotegravir) 600 mg\3 mL (Drug)
Intervention: Choice of long-acting PrEP and PEP added to Thetha Nami ngithethe nawe
Tailored peer-led psychosocial support and social mobilisation into community based SRH and differentiated HIV care and prevention, including a choice of effective PrEP or PEP.
At the mobile AYFS in the intervention clusters nurses will offer the choice of either daily oral tenofovir/emtricitabine or injectable long acting cabotegravir (CAB LA) to be delivered to adolescents and young adults at risk of HIV acquisition. Those who decline will have the option of three monthly dapivarine vaginal rings or Post Exposure Prophylaxis (PEP) packs (tenofovir/lamuvidine/dolutegravir) to take home.
Peer navigators will promote long-acting PrEP in addition to oral PrEP. As part of the peer mentorship package, the peer naviators will remind young people of their follow-up visits.
干预措施: DAPIRING (Dapivirine) 25mg Vaginal Ring (Drug)
Intervention: Choice of long-acting PrEP and PEP added to Thetha Nami ngithethe nawe
Tailored peer-led psychosocial support and social mobilisation into community based SRH and differentiated HIV care and prevention, including a choice of effective PrEP or PEP.
At the mobile AYFS in the intervention clusters nurses will offer the choice of either daily oral tenofovir/emtricitabine or injectable long acting cabotegravir (CAB LA) to be delivered to adolescents and young adults at risk of HIV acquisition. Those who decline will have the option of three monthly dapivarine vaginal rings or Post Exposure Prophylaxis (PEP) packs (tenofovir/lamuvidine/dolutegravir) to take home.
Peer navigators will promote long-acting PrEP in addition to oral PrEP. As part of the peer mentorship package, the peer naviators will remind young people of their follow-up visits.
干预措施: tenofovir disoproxil and emtricitabine (Drug)
Intervention: Choice of long-acting PrEP and PEP added to Thetha Nami ngithethe nawe
Tailored peer-led psychosocial support and social mobilisation into community based SRH and differentiated HIV care and prevention, including a choice of effective PrEP or PEP.
At the mobile AYFS in the intervention clusters nurses will offer the choice of either daily oral tenofovir/emtricitabine or injectable long acting cabotegravir (CAB LA) to be delivered to adolescents and young adults at risk of HIV acquisition. Those who decline will have the option of three monthly dapivarine vaginal rings or Post Exposure Prophylaxis (PEP) packs (tenofovir/lamuvidine/dolutegravir) to take home.
Peer navigators will promote long-acting PrEP in addition to oral PrEP. As part of the peer mentorship package, the peer naviators will remind young people of their follow-up visits.
干预措施: Tenofovir Disoproxil, Lamuvidine and Dolutegravir (Drug)
Control (Enhanced SoC): Thetha Nami ngithethe nawe
Tailored peer-led psychosocial support and social mobilisation into community based SRH and differentiated HIV care and prevention, including oral tenofovir/emtricitabine PrEP.
In the mobile AYFS, young people are offered self-taken vaginal swabs or urine testing for sexually transmitted infections (STIs), family planning support and syndromic and aetiological management for STIs; HIV counselling and two POCT; immediate initiation of ART if living with HIV and oral tenofovir/emtricitabine PrEP if HIV test is negative and they are suitable.
Peer navigators in control clusters will promote oral PrEP during their community based health promotion activities. As part of the peer mentorship package, the peer naviators will remind young people of their follow-up visits and if required accompany young people to the mobile clinics.
干预措施: tenofovir disoproxil and emtricitabine (Drug)
结局指标
主要结局
Uptake PrEP
时间窗: This will be evaluated among participants aged 16-30 years in the cross-sectional surveys at 14 months
Defined as the proportion of young people who have taken up any PrEP (oral, injectable, ring, or PEP).
Retention on PrEP
时间窗: This will be measured in the clinical cohort of consenting clinic attendeeswho start or are on PrEP/PEP during the first 10 months of the trial.
Defined as attending at least one follow-up appointment after PrEP/PEP initiation, including for HIV testing.
Uptake PrEP
时间窗: Through duration of trial, and up to 20 months
Defined as the proportion of all young people (aged 15-30) residing in the trial area (the 40 clusters) who have received any PrEP (oral, injectable, ring, or PEP) through study-linked clinics
Retention on PrEP
时间窗: 14 months
Defined as the proportion of participants enrolled at least 4 months before the end of the trial, attending at least one follow-up appointment after PrEP/PEP initiation.
次要结局
- PrEP Reach (Adoption)(14 months)
- Proportion of men and women aged 16-30 at risk of acquiring HIV or transmitting HIV(14 months)
- Adverse events(14 months)
- The prevalence of transmissible HIV.(14 months)
- PrEP delivery cost and cost-effectiveness(14 months)
- Uptake of risk informed HIV prevention(14 months)
- Uptake of contraception(14 months)
- Teenage Pregnancy(14 months)
- Curable Sexually Transmitted Infections(14 months)
- Voluntary male medical circumcision (VMMC)(14 months)
- HIV incidence(14 months)
- Recent HIV infection using recency assays(14 months)
- improved mental health(14 months)
- Patterns of PrEP/PEP use(14 months)