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

HIV Infections Clinical Trial

— LAPIS  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06250504
• Other study ID #: cRCT-PrEP-AC-001
• Status: Recruiting
• Phase: Phase 3
• Start date: February 27, 2024
• Est. completion date: March 2026

Study information

• Verified date: April 2024
• Source: Africa Health Research Institute
• Contact: Maryam G Shahmanesh, MBBChir PhD
• Phone: +447776185572
• Email: m.shahmanesh[@]ucl.ac.uk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 2000
• Est. completion date: March 2026
• Est. primary completion date: July 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 15 Years to 30 Years

Eligibility

Inclusion Criteria:

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.

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• APRETUDE (cabotegravir) 600 mg\3 mL
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.
• DAPIRING (Dapivirine) 25mg Vaginal Ring
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
• tenofovir disoproxil and emtricitabine
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
• Tenofovir Disoproxil, Lamuvidine and Dolutegravir
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

Locations

Country	Name	City	State
South Africa	Africa Health Research Institute	Somkele	KwaZulu-Natal

Sponsors (1)

Lead Sponsor	Collaborator
Africa Health Research Institute

Country where clinical trial is conducted

South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Sexual and reproductive health	uptake of family planning, teenage pregnancies and sexually transmitted infection prevalence in each arm	14 months
Other	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.	14 months
Other	improved mental health	Proportion with PHQ9 score consistent with common mental disorder in each arm	14 months
Primary	Uptake PrEP	Defined as the proportion of young people who have taken up any PrEP (oral, injectable, ring, or PEP).	This will be evaluated among participants aged 16-30 years in the cross-sectional surveys at 14 months
Primary	Retention on PrEP	Defined as attending at least one follow-up appointment after PrEP/PEP initiation, including for HIV testing.	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.
Secondary	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.	14 months
Secondary	Uptake of risk informed HIV prevention	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.	14 months
Secondary	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)	14 months
Secondary	PrEP delivery cost and cost-effectiveness	cost per effective PrEP uptake in each arm	14 months
Secondary	Adverse events	Proportion discontinue or switch due to adverse events in each arm	14 months
Secondary	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)	14 months