A Phase 3 interventional study of APRETUDE (cabotegravir) 600 mg\3 mL and DAPIRING (Dapivirine) 25mg Vaginal Ring in HIV Infections, sponsored by Africa Health Research Institute. Recruiting at 1 site in South Africa. Open to participants aged 15 Years to 30 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-07-09.
Sponsored by Africa Health Research Institute · Phase 3, Interventional, and Prevention
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.
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
4,258 studies on the registry are indexed under HIV Infections; 240 are open to participants now.
This study's planned enrollment of 2,052 is above the median of 83 across 3,251 interventional studies indexed under HIV Infections.
Browse HIV Infections studies →Africa Health Research Institute is the lead sponsor of 6 studies on the registry; 3 are open to participants now.
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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.
Exclusion Criteria:
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.
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.
Drug: APRETUDE (cabotegravir) 600 mg\3 mL · Drug: DAPIRING (Dapivirine) 25mg Vaginal Ring · Drug: tenofovir disoproxil and emtricitabine · Drug: Tenofovir Disoproxil, Lamuvidine and Dolutegravir
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.
Drug: tenofovir disoproxil and emtricitabine
choice of 2-monthly injectable long acting cabotegravir. The initial visit will be followed by planned visit for the first injection, one month visit for second injection, and then 2-monthly CAB LA injections with repeat HIV testing and pregnancy testing, and referral to peer navigators for adherence and retention support. We will conduct HIV testing, STI testing, Hep B, Hep C, and safety bloods (Full Blood Count, Creatinine, Liver Function Tests) at baseline, HIV testing two monthly, and annual safety bloods, alongside annual STI testing.
The initial visit is followed by a 7-day phone call, 3-monthly follow-up. Each follow-up will include repeat HIV testing (POCT x2 and dry blood spots for HIV ELISA) and pregnancy testing, syndromic management of STIs, and referral to peer navigators for adherence support and PrEP/ART and if applicable contraception refills. Safely bloods (full blood count, creatinine, liver function tests) will follow national guidelines. Currently we aim to do baseline and annual safety bloods, alongside annual STI testing
The initial visit is followed by a 7-day phone call, 3-monthly follow-up. Each follow-up will include repeat HIV testing (POCT x2 and dry blood spots for HIV ELISA) and pregnancy testing, syndromic management of STIs, and referral to peer navigators for adherence support and PrEP/ART and if applicable contraception refills. Safely bloods (full blood count, creatinine, liver function tests) will follow national guidelines. Currently we aim to do baseline and annual safety bloods, alongside annual STI testing
The initial visit is followed by a 7-day phone call, 3-monthly follow-up. Each follow-up will include repeat HIV testing (POCT x2 and dry blood spots for HIV ELISA) and pregnancy testing, syndromic management of STIs, and referral to peer navigators for adherence support and PrEP/ART and if applicable contraception refills. Safely bloods (full blood count, creatinine, liver function tests) will follow national guidelines. Currently we aim to do baseline and annual safety bloods, alongside annual STI testing
Uptake PrEP
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
Time frame: Through duration of trial, and up to 20 months
Retention on PrEP
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.
Time frame: 14 months
The prevalence of transmissible HIV.
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.
Time frame: 14 months
Uptake of risk informed HIV prevention
Defined as the proportion of 15-30 year olds who are aware of their HIV status and are either on PrEP, if HIV negative, or are on antiretroviral therapy if living with HIV, during final survey round.
Time frame: 14 months
Uptake of contraception
Proportion of women aged 15-30 who report currently using any contraception during final survey round
Time frame: 14 months
Teenage Pregnancy
Proportion of adolescent girls aged 15-19 years who self-report currently being pregnant in the final survey round.
Time frame: 14 months
Curable Sexually Transmitted Infections
Prevalence of any curable STIs is defined as the proportion of participants who test positive for at least one of the following infections: Chlamydia trachomatis (CT) or Neisseria gonorrhoeae (NG), based on Cepheid GeneXpert CT/NG testing measured in the final survey round
Time frame: 14 months
Voluntary male medical circumcision (VMMC)
Proportion of male participants who report ever having undergone circumcision in the final survey round
Time frame: 14 months
Proportion of men and women aged 16-30 at risk of acquiring HIV or transmitting HIV
If living with HIV (a detectable viral load + condomless sex + not on ART), or, if not living with HIV (condomless sex + not on PrEP)
Time frame: 14 months
HIV incidence
The rate of new infections in the PrEP cohort irrespective of PrEP use
Time frame: 14 months
Recent HIV infection using recency assays
Proportion of those living with HIV in the end-line survey with a positive recency assay on DBS
Time frame: 14 months
improved mental health
Proportion with PHQ9 score consistent with common mental disorder in each arm
Time frame: 14 months
PrEP Reach (Adoption)
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)
Time frame: 14 months
Adverse events
frequency and severity of adverse events associated with CABLA compared to oral PrEP.
Time frame: 14 months
PrEP delivery cost and cost-effectiveness
cost per effective PrEP uptake in each arm
Time frame: 14 months
Patterns of PrEP/PEP use
Longitudinal patterns of PrEP and PEP initiation, switching and stopping within the choice arm
Time frame: 14 months
Improved socioeconomic outcomes
Defined as proportion in school (aged \<= 18) or unemployed (aged \>18) and/or food secure (no recent experience of hunger) in each arm.
Time frame: 14 months
Documents are hosted by the registry — open the source record to download them.
Plan to share: Yes
Supporting information: Study protocol, Sap, Icf, Csr, Analytic code
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Africa Health Research Institute