Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0835 or +27 21 938 0967
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202607711608317 Date of Registration: 22/07/2026
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title SUpporting PRogrammatic maternal viral SUPPRESSION with Long-Acting therapy
Official scientific title Switching to long-acting cabotegravir + lenacapavir during pregnancy: a non-inferiority trial of pragmatic test-and-treat-then-switch in late pregnancy and postpartum.
Brief summary describing the background and objectives of the trial Background and Objectives of the Trial The trial is designed to address the ongoing need for effective, safe, and scalable treatment strategies for HIV in pregnant women, a population at increased risk of adverse maternal and neonatal outcomes. While standard antiretroviral therapy (e.g., Tenofovir/Lamivudine/Dolutegravir [TLD]) has demonstrated high efficacy, challenges remain related to adherence, long-term tolerability, and maintaining viral suppression throughout pregnancy and the postpartum period. Long-acting antiretroviral agents, such as cabotegravir and lenacapavir, offer a promising alternative due to their extended dosing intervals, which may improve adherence, reduce pill burden, and enhance treatment continuity. However, there is limited evidence on their safety, pharmacokinetics, and efficacy in pregnant populations. Primary Objective: To evaluate the efficacy of long-acting cabotegravir plus lenacapavir compared to standard oral TLD in achieving and maintaining viral suppression in pregnant women living with HIV. Secondary Objectives: To assess the safety and tolerability of the investigational regimen in both mothers and infants To evaluate maternal and neonatal outcomes, including birth outcomes and HIV transmission rates To characterize pharmacokinetics of the study drugs during pregnancy and postpartum To assess adherence, acceptability, and feasibility of long-acting therapy in this population
Type of trial RCT
Acronym (If the trial has an acronym then please provide) SUPPRESS LA
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied HIV/AIDS
Purpose of the trial Treatment: Drugs
Anticipated trial start date 01/10/2026
Actual trial start date
Anticipated date of last follow up 15/06/2030
Actual Last follow-up date 31/12/2030
Anticipated target sample size (number of participants) 630
Actual target sample size (number of participants)
Recruitment status Not yet recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Simple randomization using by using procedures such as coin-tossing or dice-rolling Allocation Sequence/Code was not concealed Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group CAB LEN Cabotegravir (IM, gluteal): 600 mg at Day 0 and Day +56, then 600 mg every 8 weeks thereafter (±7-day maintenance window). Lenacapavir oral loading (PO): 600 mg on Day 0, 600 mg on Day +1, and 300 mg on Day +7. Lenacapavir (SC, abdominal wall, given as two 1.5 mL injections): 927 mg at Day +14, then 927 mg every 26 weeks thereafter (including ≈Day +196), ±14-day maintenance window. TLD bridge (Arm 2 only) Same TLD tablet (DTG 50 mg + TDF 300 mg + 3TC 300 mg) once daily, from the evening of Day -3 (universal test-and-treat lead-in) through the morning of Day +14 (discontinued on the day of the first LEN SC injection). CAB every 8 weeks, LEN every 26 weeks Regimen. Long-acting injectable cabotegravir (CAB; GSK1265744, Vocabria) combined with long-acting subcutaneous lenacapavir (LEN; GS-6207, Sunlenca), initiated during pregnancy and continued through postpartum follow-up. Cabotegravir is an integrase strand transfer inhibitor (INSTI) supplied as a 200 mg/mL nanosuspension; lenacapavir is a first-in-class capsid inhibitor supplied as a 463.5 mg/1.5 mL solution for SC injection and as 300 mg oral tablets for loading. The combination is investigational in pregnancy for both treatment initiation and maintenance. Initiation sequence (anchored to Day 0 randomisation): Day -3: universal oral TLD lead-in started that evening (all participants, both arms). Day 0: randomisation; CAB 600 mg IM (gluteal) dose 1 + LEN 600 mg PO oral loading dose 1. TLD bridge continues. Day +1: LEN 600 mg PO oral loading dose 2 (home dose). TLD continues. Day +7: LEN 300 mg PO oral loading dose 3. TLD continues; brief phone contact. Day +14: first LEN 927 mg SC injection (two 1.5 mL injections, abdominal wall). TLD oral bridge discontinued that morning. Day +56: CAB 600 mg IM dose 2. Maintenance dosing: Cabotegravir 600 mg IM every 8 weeks (±7-day window). Lenacapavir 927 mg SC every 26 weeks (±14-day window), including approximately Day +196. TLD bridge. A protocol-defined oral TLD bridge (DTG 50 mg + TDF 300 mg + 3TC 300 mg once daily) runs from the Day -3 evening lead-in through the morning of Day +14, covering the LEN oral-loading-to-first-SC-injection window. Per the SAP, this bridge is part of the assigned CAB+LEN regimen and does not constitute a per-protocol deviation. Administration details. CAB is given as a deep gluteal IM injection, alternating left/right sites at successive visits; participants are counselled to avoid massaging the gluteal site for ≥48 hours to avoid disrupting the depot. LEN SC is given as two abdominal-wall injections at separate sites, rotated left/right at successive visits. Support / contingency elements. Missed or delayed injections are managed via the missed-dose, reload, and oral-bridging pathways (Sections 6.4.4, 6.11.3). At Day +14, where locally approved, sites dispense an Emergency Bridging Kit (sealed 30-day TLD supply for home storage) or operate a Community Health Worker home-delivery track (14-day TLD bridge), to maintain coverage during unanticipated gaps in clinic-based dosing. Duration. Through 12 months postpartum (primary endpoint), with continuation through end of breastfeeding where applicable. 315
Control Group TLD TLD fixed-dose combination — tenofovir disoproxil fumarate 300 mg + lamivudine 300 mg + dolutegravir 50 mg. Dose and frequency: One tablet once daily (oral), per national guidelines. Through 12 months postpartum (primary endpoint), with continuation through end of breastfeeding where applicable. TLD fixed-dose combination: tenofovir disoproxil fumarate 300 mg + lamivudine 300 mg + dolutegravir 50 mg, one tablet once daily, continued through 12 months postpartum (primary endpoint) and through end of breastfeeding where applicable. 315 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Pregnancy and HIV diagnosis Pregnant woman aged ≥18 years (or ≥16 years where the country-specific appendix authorises; see country appendices). Confirmed intrauterine pregnancy by transabdominal ultrasound prior to randomisation. Gestational age 14–32 weeks (inclusive) at randomisation, dated by best-obstetric-estimate. Confirmed HIV-1 infection per the protocol-specified diagnostic algorithm. Detectable plasma HIV-1 RNA at screening, defined as HIV-1 RNA ≥50 copies/mL by central-laboratory assay reviewed before Day 0 randomisation. (Qualified point-of-care viral-load platforms may be used for internal triage or QC but do not replace central confirmation for randomisation.) ART history ART-naive first-time HIV diagnosis at the antenatal-entry visit, OR no prior antiretroviral exposure documented in clinic records or self-report; OR Previously on ART but off ART for ≥28 calendar days at the time of screening, regardless of reason for prior discontinuation. Prior virologic failure does not disqualify. Capacity and consent Willing and able to provide informed consent (or assent with co-consent per the country-specific appendix for ages 16–17 where applicable). Willing to attend study visits and complete contacts per the Schedule of Activities, including the Day -3, Day 0, Day +1, Day +7, and Day +14 initiation-period requirements where applicable. Willing to receive long-acting injections (CAB intramuscular and LEN subcutaneous) if randomised to the investigational arm. Active opportunistic infection requiring inpatient care or systemic therapy at screening. Known hypersensitivity to cabotegravir, lenacapavir, tenofovir, lamivudine, or dolutegravir. Current use of a prohibited concomitant medication (Section 6.11.1). Grade 3 or higher renal impairment (eGFR <30 mL/min/1.73 m² by CKD-EPI) at screening. Grade 3 or higher hepatic impairment (ALT or AST >5× upper limit of normal) at screening. Active hepatitis B or hepatitis C infection requiring antiviral therapy that is incompatible with the assigned regimen. Multiple gestation (≥2 fetuses) where the obstetric care plan precludes participation in the protocol. Major fetal anomaly identified at the screening or baseline ultrasound that in the investigator's judgement warrants exclusion. Active substance use disorder uncontrolled by treatment that the investigator judges incompatible with safe study participation. Concurrent enrolment in another investigational drug or device trial. Adult: 18 Year(s)-44 Year(s) 16 Year(s) 44 Year(s) Female
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
No 31/07/2026 MCAZ
Ethics Committee Address
Street address City Postal code Country
106 Baines Avenue Harare 0000 Zimbabwe
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
No 31/07/2026 SAHPRA
Ethics Committee Address
Street address City Postal code Country
Building A, Loftus Park, 402 Kirkness Street, Arcadia, Pretoria X828 South Africa
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
No 15/08/2026 Uganda NDA
Ethics Committee Address
Street address City Postal code Country
NDA Tower, Plot 93 Buganda Road Kampala 23096 Uganda
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Maternal virologic suppression (HIV-1 RNA <50 copies/mL) 12 months postpartum
Secondary Outcome Early MTCT (confirmed infant HIV-1 infection) Birth, confirmed through 6 weeks postpartum
Secondary Outcome Cumulative MTCT (confirmed infant HIV-1 infection) Birth through 12 months postpartum
Secondary Outcome Maternal virologic suppression at delivery (descriptive) At delivery
Secondary Outcome Maternal and infant safety (AEs/SAEs) Randomisation through 12 months postpartum
Secondary Outcome Retention in care 12 months postpartum
Secondary Outcome Adherence to assigned regimen(composite) Through 12 months postpartum
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
mutala clinical research site 52 Alpes Vainona Harare Zimbabwe
Desmond Tutu Health Foundation 3 Woodlands Road, Woodstock, 7925 Cape Town South Africa
Makerere University Johns Hopkins University Research Collaboration Upper Mulago Hill Road Kampala 23491 Uganda
FUNDING SOURCES
Name of source Street address City Postal code Country
Bill and Melinda gates Medical research reseearch institute One Kendall Square Cambridge 02139 United States of America
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Africa Clinical Research Network C1-402, 4th floor, Block C Grand Baie Mauritius Charities/Societies/Foundation
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Scientific Enquiries Chiratidzo Ellen Ndhlovu rati.ndhlovu@acrnhealth.com +263772412701 52 Alpes, Vainona
City Postal code Country Position/Affiliation
Harare Zimbabwe Executive Director Mutala Clinical Research Site
Role Name Email Phone Street address
Public Enquiries Romina Mariano romina.mariano@acrnhealth.com +27797445305 52 Alpes, Vainona
City Postal code Country Position/Affiliation
Harare Zimbabwe Chief of Staff Africa Clinical Research Network
Role Name Email Phone Street address
Principal Investigator Azure Tariro Makadzange tariro.makadzange@acrnhealth.com +18572008374 52 Alpes, Vainona
City Postal code Country Position/Affiliation
Harare Zimbabwe CEO Africa Clinical Research Network
Role Name Email Phone Street address
Principal Investigator Flavia Matovu Kiweewa fmatovu@musph.ac.ug +256414541044 Upper Mulago Hill Road
City Postal code Country Position/Affiliation
Kampala 23491, Uganda Makerere University Johns Hopkins University Research Collaboration
Role Name Email Phone Street address
Principal Investigator Linda Gail berker linda-gail.bekker@hiv-research.org.za +27216506959 3 Guinea Fowl Road Cape Town 7975
City Postal code Country Position/Affiliation
Cape Town 0000 South Africa Director
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Individual participant data will be available (including data dictionaries). The data to be shared is individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures and appendices). Informed Consent Form,Statistical Analysis Plan,Study Protocol Beginning 7months ending 5 years after publication Proposals should be directed to Tariro.makadzange@acrnhe alth.com To gain access, data requestors will need to sign a data requestors access agreement. Data will be shared with investigators whose proposed use of the data has been approved by the ACRN senior management team for individual participant data meta-analyses.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information
Section Name Field Name Date Reason Old Value Updated Value
Eligibility Age group 15/07/2026 ticked the wrong box Adult: 18 Year(s)-44 Year(s), Middle Aged: 45 Year(s)-64 Year(s) Adult: 18 Year(s)-44 Year(s)
Section Name Field Name Date Reason Old Value Updated Value
Eligibility Age group 15/07/2026 ticked the wrong box Adult: 18 Year(s)-44 Year(s), Middle Aged: 45 Year(s)-64 Year(s) Adult: 18 Year(s)-44 Year(s)
Section Name Field Name Date Reason Old Value Updated Value
Contact People Contacs List 15/07/2026 had left out the principal for south africa Principal Investigator, Linda Gail, berker, Prof., linda-gail.bekker@hiv-research.org.za, , +27216506959, 3 Guinea Fowl Road Cape Town 7975, Cape Town , 0000, South Africa, Director
Section Name Field Name Date Reason Old Value Updated Value
Eligibility Maximum age 15/07/2026 typing error 65 Year(s) 44 Year(s)
Section Name Field Name Date Reason Old Value Updated Value
Eligibility Maximum age 15/07/2026 typing error 65 Year(s) 44 Year(s)