Clinical trial NCT06250504: Long-Acting HIV Pre-Exposure Prophylaxis Integrated With Sexual and Reproductive Health - cRCT
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: HIV Infections
Lead sponsor: Africa Health Research Institute
Sponsor class: OTHER
First posted: 2024-02-09
Enrollment: 2000
Sex: ALL
Minimum age (years): 15
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A hybrid phase 3B effectiveness implementation type 1a cluster randomised control trial (cRCT)
Primary purpose: PREVENTION

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

Eligibility criteria: 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.

Primary outcomes:
measure: Uptake PrEP
timeFrame: This will be evaluated among participants aged 16-30 years in the cross-sectional surveys at 14 months
measure: Retention on PrEP
timeFrame: 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 outcomes:
measure: The prevalence of transmissible HIV.
timeFrame: 14 months
measure: Uptake of risk informed HIV prevention
timeFrame: 14 months
measure: PrEP Reach (Adoption)
timeFrame: 14 months
measure: PrEP delivery cost and cost-effectiveness
timeFrame: 14 months
measure: Adverse events
timeFrame: 14 months
measure: Proportion of men and women aged 16-30 at risk of acquiring HIV or transmitting HIV
timeFrame: 14 months
Other outcomes:
measure: Sexual and reproductive health
timeFrame: 14 months
measure: Improved socioeconomic outcomes
timeFrame: 14 months
measure: improved mental health
timeFrame: 14 months
Locations:
city: Somkele
country: South Africa
facility: Africa Health Research Institute
state: KwaZulu-Natal
Study officials:
References: