ComBaCaL HIV Prevention TwiCs (CoPrev)

Community-based, Village Health Worker-led, eHealth-supported, Integrated HIV Prevention for People at Substantial Risk of HIV Acquisition in Rural Lesotho: Protocol for a Cluster-randomized Hybrid Type 1 effectiveness-implementation Trial Within the ComBaCaL Cohort Study

This cluster-randomized intervention is embedded in the ComBaCaL (Community-Based Chronic disease care Lesotho) cohort study (EKNZ ID AO_2022-00058, clinicaltrials.gov ID NCT05596773, Lesotho NH-REC ID 210-2022), a platform for the investigation of chronic diseases and their management in rural Lesotho that is maintained by local lay chronic care village health workers (CC-VHWs).

This study is to evaluate the effectiveness and safety of the CoPrev model in regard to biomedical HIV prevention utilization compared with an enhanced standard of care, in which VHWs assisted by a tablet-based CDS application, perform the same activities except for the prescription and/or delivery of PEP, oral PrEP, COC and self-injectable contraception. Additionally, this study aims to assess the outcomes and processes related to the implementation of such a model.

Study Overview

• Status: Not yet recruiting
• Conditions: Human Immunodeficiency Virus (HIV)
• Intervention / Treatment: Other: CoPrev model; Other: Referral to the nearest responsible health facility

Detailed Description

Approximately 1.3 million new HIV infections were reported worldwide in 2024. Eastern and Southern Africa continue to bear the largest share of the HIV-related burden. To prevent lingering epidemics in these low-resource, high-prevalence regions, it is essential to intensify HIV prevention efforts, including the scale-up of effective biomedical HIV prevention, such as Pre-Exposure (PrEP) and Post- Exposure Prophylaxis (PEP). However, uptake, persistent use and adherence to biomedical HIV prevention remains low among individuals at substantial risk of HIV acquisition, especially in rural areas. Thus, there is an urgent need for scalable, integrated, cost-effective, and context-specific service delivery models that increase the utilization of biomedical HIV prevention among populations at increased risk in Southern Africa.

This cluster-randomized intervention is embedded in the ComBaCaL (Community-Based Chronic disease care Lesotho) cohort study (EKNZ ID AO_2022-00058, clinicaltrials.gov ID NCT05596773, Lesotho NH-REC ID 210-2022), a platform for the investigation of chronic diseases and their management in rural Lesotho that is maintained by local lay chronic care village health workers (CC-VHWs).

The ComBaCaL HIV Preven7on (CoPrev) model is a differen7ated, community-based preven7on model, that provides eligible individuals with an alterna7ve to facility-based HIV preven7on and contracep7on. It builds on the broader ComBaCaL model of care, which extends the role of VHWs beyond educa7on, counselling, screening, and referral, to include ac7ve management of preven7on and care services for selected condi7ons. This is enabled through a tablet-based CDS applica7on, allowing VHWs to independently prescribe and deliver selected medica7ons at community level.

Within the CoPrev model, VHWs, assisted by the CDS application, deliver an integrated HIV prevention package comprising HIV prevention education and counselling; HIV and HIV risk screening; condom provision; referral to health facilities, and the prescription and delivery of PEP (TDF/3TC/DTG) and oral PrEP (TDF/3TC) to those eligible. In addition, VHWs provide contraceptive services, including family planning education and counselling; pregnancy screening; referral to health facilities; and the delivery of refills of combined oral contraception (COC) and self-injectable contraception to those eligible.

• Study Type: Interventional
• Enrollment (Estimated): 380
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Niklaus Labhardt, Prof. Dr.; Phone Number: +41 79 870 18 59; Email: niklaus.labhardt@usb.ch

Study Locations

• Lesotho
  • Maseru, Lesotho
    • SolidarMed Lesotho
    • Principal Investigator: Irene Ayakaka, MD
    • Contact: Irene Ayakaka, MD; Phone Number: +266 2832 5172
    • Sub-Investigator: Ravi Gupta, MD
    • Principal Investigator: Tarumbiswa Tapiwa, MD
    • Sub-Investigator: Nthuseng BridgeI Marake, MD
    • Sub-Investigator: Rosina Phate, MSc
    • Sub-Investigator: Mamotena Sekhobe, MD
• Switzerland
  • Basel, Switzerland, 4051
    • University of Basel, Division of Clinical Epidemiology
    • Contact: Niklaus Labhardt, Prof Dr; Phone Number: +41 79 870 18 59; Email: niklaus.labhardt@usb.ch
    • Principal Investigator: Niklaus Labhardt, Prof Dr
    • Sub-Investigator: Alain Amstutz, MD/PhD
    • Sub-Investigator: Felix Gerber, MD/PhD
    • Sub-Investigator: Fabian Raeber, MSc
    • Sub-Investigator: Elis Saavedra, MSc
    • Sub-Investigator: Palesa Agnes Mahlatsi, MSc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Participant of the ComBaCaL cohort study (signed informed consent available)
• Weight ≥ 35 kg
• Negative HIV screening test
• No potential exposure to HIV more than 72 hours ago (PEP eligibility window period) and less than 4 weeks ago (window period HIV test)

• At substantial risk of HIV acquisition as per behavioural risk factors in the Lesotho's national HIV prevention and treatment guidelines:

  • Report of serodiscordant partner who are not virally suppressed or have an unknown viral suppression status (either not on ART, initiated ART within the last 6 months, known virally unsuppressed or unknown virally suppression status but believed not to be taking treatment regularly)
  • Report of sexual partner with unknown HIV status
  • Report of unprotected sex with more than one partner in the last 6 months
  • Report of STI by lab-testing or self-report of STI syndromic management in the last 6 months
  • Report of exchanging money/goods for sex in the last 6 months (as recipient and vice versa)
  • Report of intravenous drug use with shared equipment in the last 6 months
  • Request for biomedical HIV prevention

Exclusion Criteria:

• Known allergies to PEP/oral PrEP
• Known glomerular filtration rate (GFR) < 60 ml/min or diagnosis of moderate/severe kidney disease or kidney failure

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Intervention villages; In the intervention villages, VHWs will follow the standard service protocol of the ComBaCaL cohort study, but in line with the CoPrev model, will also be able to additionally prescribe and deliver drugs for biomedical HIV prevention (PEP (TDF/3TC/DTG 300mg/300mg/50mg) or oral PrEP (TDF/3TC 300mg/300mg)) and offer refills for contraception (EE/LNG 30mcg/15mcg or 50mcg/15mcg) or self-injectable contraception (s.c. 104mg/0.65ml medroxypregosteronacetate). VHWs will provide monitoring for all dispensed drug regimens, thereby ensuring comprehensive and integrated sexual and reproductive health services within their communities.	Other: CoPrev model; prescribe and deliver drugs for biomedical HIV prevenTion (PEP (TDF/3TC/DTG 300mg/300mg/50mg) or oral PrEP (TDF/3TC 300mg/300mg)); offer refills for contraception (EE/LNG 30mcg/15mcg or 50mcg/15mcg) or self-injectable contraception (s.c. 104mg/0.65ml medroxypregosteronacetate; monitoring for all dispensed drug regimens
Active Comparator: Control villages; In the control villages, VHWs will follow the standard service protocol of the ComBaCaL cohort study. Using the tablet-based CDS application, they will be trained and supervised to educate participants on HIV prevention, screen for HIV offering oral HIV self-tests, assess HIV risk behaviour, provide risk reduction counselling and condoms, and refer participants eligible for biomedical HIV prevention to the nearest health facility. Furthermore, they will offer family planning education, pregnancy screening, and refer participants for contraception.	Other: Referral to the nearest responsible health facility; refer participants eligible for biomedical HIV prevention to the nearest health facility; offer family planning education, pregnancy screening, and refer participants for contraception.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Monthly biomedical HIV prevention coverage over 6 months after enrolment	Biomedical HIV prevention coverage is defined at the person- month level as a binary indicator of whether a participant was covered by a biomedical HIV prevention method (PEP (TDF/3TC/DTG), oral PrEP (TDF/3TC), or injectable PrEP) during a given 30-day month within the six-month observation period following enrolment in the ComBaCaL HIV prevention TwiCs .	Single assessment visit scheduled approximately six months after enrolment (180 days)

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Collaborators: SolidarMed; Swiss Agency for Development and Cooperation (SDC); World Diabetes Foundation (WDF)
• Investigators: Principal Investigator: Niklaus Labhardt, Division of Clinical Epidemiology, University Hospital Basel

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: May 5, 2026
• First Submitted That Met QC Criteria: May 5, 2026
• First Posted (Actual): May 12, 2026

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 18, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Post-Exposure Prophylaxis (PEP); Community health worker (CHW); Levonorgestrel (LNG); Pre-Exposure Prophylaxis (PrEP); Clinical decision support (CDS); Antiretroviral therapy (ART); Dolutegravir (DTG); Community-Based Chronic Disease Care Lesotho (ComBaCaL) cohort study; Ethinylestradiol (EE); Lamivudine (3TC); Trials within Cohorts (TwiCs); Low- and middle-income countries (LMICs); Adolescent girls and young women (AGYW); Village health worker (VHW); Tenofovir Disoproxil Fumarate (TDF); Combined oral contraception (COC); Sexually transmitted infection (STI)
• Additional Relevant MeSH Terms: Blood-Borne Infections; Urogenital Diseases; Genital Diseases; Pathologic Processes; Disease Attributes; Immune System Diseases; Infections; RNA Virus Infections; Virus Diseases; Communicable Diseases; Sexually Transmitted Diseases, Viral; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Slow Virus Diseases; HIV Infections; Pathological Conditions, Signs and Symptoms; Acquired Immunodeficiency Syndrome; Sexually Transmitted Diseases
• Other Study ID Numbers: ub26Labhardt2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: An anonymized key dataset necessary for reproducing the primary and key secondary endpoints will be made freely available in an appropriate repository, such as zenodo.org, alongside the publication of the study results. Besides removal of variables not required for key analysis, we will remove participant identifier, study site and exact date information. Requests for access to more detailed data may be made to the corresponding author by submitting a proposal, which will be reviewed by the trial consortium.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No