Long-Acting HIV Pre-Exposure Prophylaxis Integrated With Sexual and Reproductive Health - cRCT

NCT06250504 | Recruiting Phase 3 DMC

• 1 other identifier: cRCT-PrEP-AC-001
• Study Type: interventional
• Target: 2,052
• Locations: 1 country
• Sites: 1

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.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (2)

• 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

  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.

  14 months

Secondary Outcomes (14)

• The prevalence of transmissible HIV.

  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

Other Outcomes (1)

• Improved socioeconomic outcomes

  14 months

Study Arms (2)

Intervention: Choice of long-acting PrEP and PEP added to Thetha Nami ngithethe nawe

EXPERIMENTAL

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

Control (Enhanced SoC): Thetha Nami ngithethe nawe

ACTIVE COMPARATOR

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

Interventions

APRETUDE (cabotegravir) 600 mg\3 mL DRUG

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.

Intervention: Choice of long-acting PrEP and PEP added to Thetha Nami ngithethe nawe

DAPIRING (Dapivirine) 25mg Vaginal Ring DRUG

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

Intervention: Choice of long-acting PrEP and PEP added to Thetha Nami ngithethe nawe

tenofovir disoproxil and emtricitabine DRUG

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

Control (Enhanced SoC): Thetha Nami ngithethe nawe; Intervention: Choice of long-acting PrEP and PEP added to Thetha Nami ngithethe nawe

Tenofovir Disoproxil, Lamuvidine and Dolutegravir DRUG

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

Intervention: Choice of long-acting PrEP and PEP added to Thetha Nami ngithethe nawe

Eligibility Criteria

• Age: 15 Years - 30 Years
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• History or presence of allergy to the study drugs or their components
• Investigator assessment find them not suitable
• 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.

Sponsors & Collaborators

• Africa Health Research Institute: lead

Study Sites (1)

Africa Health Research Institute

Somkele, KwaZulu-Natal, South Africa

RECRUITING

Related Publications (1)

• Busang J, Zuma T, Chimbindi N, Ngoma N, Herbst C, Okesola N, Dreyer J, Smit T, Bird K, Mtolo L, Behuhuma N, Lebina L, Hendrickson C, Miot J, Hanekom W, Herbst K, Seeley J, Copas A, Baisley K, Shahmanesh M; LAPIS Study Team. Long-acting HIV pre-exposure prophylaxis integrated with community-based sexual and reproductive health services in South Africa (LAPIS): study protocol for a hybrid (1a) cluster randomised controlled phase 3B trial of effectiveness and implementation. BMC Public Health. 2026 Jan 20;26(1):610. doi: 10.1186/s12889-025-24889-1.

  PMID: 41559582 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

cabotegravir; Dapivirine; Contraceptive Devices, Female; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Tenofovir; dolutegravir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Contraceptive Devices; Equipment and Supplies; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Emtricitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations

Central Study Contacts

Maryam G Shahmanesh, MBBChir PhD

CONTACT

+447776185572; m.shahmanesh@ucl.ac.uk

Limakatso Lebina, MBBS PhD

CONTACT

l.lebina@ucl.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A hybrid phase 3B effectiveness implementation type 1a cluster randomised control trial (cRCT)

Study Record Dates

• First Submitted: December 15, 2023
• First Posted: February 9, 2024
• Study Start: February 27, 2024
• Primary Completion: April 30, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: July 9, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: After the primary analysis has been completed and publicaly shared

Locations

ZA (1)