Long-Acting HIV Pre-Exposure Prophylaxis Integrated With Sexual and Reproductive Health - cRCT
- Conditions
- HIV Infections
- Interventions
- Drug: DAPIRING (Dapivirine) 25mg Vaginal Ring
- Registration Number
- NCT06250504
- Lead Sponsor
- Africa Health Research Institute
- Brief Summary
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.
- Detailed Description
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
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 2000
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.
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Intervention: Choice of long-acting PrEP and PEP added to Thetha Nami ngithethe nawe tenofovir disoproxil and emtricitabine 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. Intervention: Choice of long-acting PrEP and PEP added to Thetha Nami ngithethe nawe Tenofovir Disoproxil, Lamuvidine and Dolutegravir 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. Control (Enhanced SoC): Thetha Nami ngithethe nawe tenofovir disoproxil and emtricitabine 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. Intervention: Choice of long-acting PrEP and PEP added to Thetha Nami ngithethe nawe APRETUDE (cabotegravir) 600 mg\3 mL 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. Intervention: Choice of long-acting PrEP and PEP added to Thetha Nami ngithethe nawe DAPIRING (Dapivirine) 25mg Vaginal Ring 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.
- Primary Outcome Measures
Name Time Method Uptake PrEP 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 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.
- Secondary Outcome Measures
Name Time Method Uptake of risk informed HIV prevention 14 months Defined as the proportion of 16-30 year olds who are aware of their HIV status and have undergone a HIV risk assessment to inform HIV prevention and/or are on/start HIV treatment if living with HIV.
PrEP Reach (Adoption) 14 months Proportion of those at greatest risk adopting (taking up) PrEP or PEP in each arm. Greatest risk is defined as an aggregate exposure disaggregated by gender that includes any of the following factors: out of school (aged \<= 18) or unemployed (aged \>18) and/or engaged in transactional sex or sex work and/or harmful alcohol use (AUDIT scale) and/or experience physical, sexual or emotional violence (validated tool) and/or food poverty (recent experience of hunger)
Proportion of men and women aged 16-30 at risk of acquiring HIV or transmitting HIV 14 months If living with HIV (a detectable viral load + condomless sex + not on ART), or, if not living with HIV (condomless sex + not on PrEP)
Adverse events 14 months Proportion discontinue or switch due to adverse events in each arm
The prevalence of transmissible HIV. 14 months We will measure this outcome as the proportion of those living with HIV and have a detectable HIV viral load, defined as having an HIV viral load of \>= 400 copies per ml, during our final survey round.
PrEP delivery cost and cost-effectiveness 14 months cost per effective PrEP uptake in each arm
Trial Locations
- Locations (1)
Africa Health Research Institute
🇿🇦Somkele, KwaZulu-Natal, South Africa