ALIGN: A Non-randomised Study Delivering Injectable Lenacapavir for HIV Prevention Within a Pre-exposure Prophylaxis (PrEP) Choice Context in Cape Town, South Africa.

NCT07390409 | Not Yet Recruiting FDA Drug

• 2 other identifiers: ALIGNINV06512
• Study Type: observational
• Target: 3,700
• Locations: 1 country
• Sites: 1

Brief Summary

The ALIGN study will evaluate the delivery of injectable Lenacapavir (LEN), a long-acting injectable formulation for HIV pre-exposure prophylaxis (PrEP), amongst adolescents and young people (aged 15-35 years) living within the Klipfontein-Mitchell's health sub-district of Cape Town, South Africa. LEN will be offered alongside injectable Cabotegravir long-acting (CAB LA), an injectable PrEP product already approved for use in South Africa, and oral PrEP (F/TDF) modalities (including intermittent dosing where appropriate), the current standard of care (SOC) biomedical HIV prevention in South Africa. Following counselling, participants will be able to choose which PrEP product (LEN, CAB LA, or oral PrEP) to initiate, with the option to switch at any future clinical visit, and followed for 18 months. These options will be offered from two types of delivery sites, namely public health facilities and established mobile service delivery trucks, where various forms of PrEP are currently delivered as part of outreach services and ongoing research studies (FastPrEP UCT HREC nr. 713/2021 and PrEPared to Choose 567/2023). Lenacapavir (LEN) is a novel, first-in-class, multi-stage HIV-1 capsid inhibitor with high potency and a long half-life, allowing administration by subcutaneous injection twice yearly (1). The PURPOSE 1 study, a phase 3, double-blind, randomized, controlled trial involved adolescent girls and young women in South Africa and Uganda. Purpose 1 study found that none of the participants receiving twice-yearly LEN injection acquired HIV infection (1). Purpose 2, which was conducted amongst cisgender men who have sex with men, transgender, and non-binary populations, reported two incident infections amongst 2179 LEN users. CAB LA is an alternative long-acting injectable formulation administered by intra-muscular injection every two months. CAB LA efficacy and safety was established in the HPTN 083 and HPTN 084 studies, which indicated a 66% and 88% reduction in HIV risk compared to oral PrEP users respectively. The ongoing PrEPared to Choose study, conducted by this study team, (UCT HREC 567/2023) offers CAB LA and oral PrEP products and has demonstrated the feasibility and impact of many of the PrEP choice and delivery processes put forward in this protocol. As such, this study team has extensive experience in CAB LA and oral PrEP real-world delivery. The ALIGN study will provide one of the first real-world (outside of the clinical trial research site) evaluations of LEN delivery with the view to evaluate firstly, what implementation strategies best support LEN initiation and persistence at the level of the PrEP provider and the PrEP user, and secondly, persistence (defined as consistent, uninterrupted use as prescribed) on LEN compared to alternative injectable products and SOC oral PrEP. The proposed study will utilise a hybrid implementation study design, with co-primary implementation and clinical aims, in the form of a non-randomised, quasi-experimental trial design. Findings from this study will be used to inform the anticipated LEN rollout into public health facilities (including ANC clinics) as well as the implementation of PrEP choice service delivery in a new era of expanded biomedical HIV prevention products. The addition of LEN will build on the experiences of implementing previous long-acting PrEP products (such as injectable long-acting Cabotegravir) and will generate practical insights to inform the scale of this innovative tool while national regulatory approvals are being sought. This will include working with communities to harness their insights and answering specific questions to support effective delivery and drive uptake and effective use of injectable PrEP (LEN and CAB LA). Study purpose: To evaluate the delivery strategies (public health facility and community-based) and potential impact of Lenacapavir (LEN) as PrEP, on the relative persistence of up to 3700 young people (aged 15-35 years) initiating on LEN compared to an alternative injectable product (CAB LA) and oral PrEP products (standard of care). We hypothesize that people who select injectable PrEP will be more likely to persist on PrEP when compared with people who select oral PrEP, and further that injectable LEN will show enhanced persistence compared to injectable CAB LA. Primary study objectives: The primary objectives of this study are to distinguish PrEP persistence patterns across different PrEP modalities (oral PrEP vs injectable CAB vs injectable LEN as PrEP) and identify successful implementation strategies that will aid the provision of PrEP choice to adolescents and young people in South Africa from two distinct delivery platforms (public health facilities and mobile services).

Conditions

HIV

Keywords

Lenacapavir; Pre-exposure prophylaxis; PrEP choice; Cabotegravir

Outcome Measures

Primary Outcomes (1)

• To compare persistence between PrEP modalities (injectable LEN vs injectable CAB LA vs oral PrEP) longitudinally (time to non-persistence) and segmentally (total time over which biomedical coverage of HIV exposure is achieved.

  Persistence is defined as continuous use of product as intended. This will be measured in two ways: 1\. Longitudinal view of persistence: time to meet criteria for non-persistence from baseline. This view will be presented through a Kaplan-Meier analysis. • Non-persistence: Defined as \>28 days gap in PrEP availability for daily dosing (oral PrEP); \>28 days gap in scheduled CAB LA injections as per pharmacy records; and as a ≥14 days gap following a scheduled LEN injection * Non-persistence may also arise if a participant discontinues PrEP but then recommences PrEP within the study timeline. * If a participant switches to using another PrEP product (with less than 14 day gap between products), they will be considered non-persistent on that individual PrEP product but persistent on PrEP overall. * If a participant defers a LEN or CAB LA injection for scheduling reasons, oral may be used as a "bridge" between injections. Participants that bridge will be defined as persistent.

  Measured at 6, 12 months and 18 months

Interventions

Cabotegravir (CAB) LA DRUG

CABLA given every 2 months as HIV prevention

Lenacapavir Injection DRUG

Lenacapavir given every 6 months for HIV prevention.

Tenofovi-Emtricitabine (TDF/FTC) tablet DRUG

Oral PrEP (TDF/FTC) taken daily for HIV prevention

Eligibility Criteria

• Age: 15 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

People accessing the sites (mobile clinics in Cape Town, South Africa) for general sexual and reproductive health services including PrEP will be invited to consecutively enrol on the ALIGN project. If enrolled on ALIGN, they will be able to select their preferred PrEP modalities (oral PrEP, LEN or CAB LA) to use for the duration of the study (18 months).

You may qualify if:

• All participants must be HIV negative at baseline
• \- 15-35 years
• All participants must have a body weight ¬\> 35kg at baseline
• All participants must be currently resident in the study area
• All participants must be able to provide written, informed voluntary consent to partake in the study and willing and able to receive an injectable PrEP product
• All participants must be sexually active (has had ≥ 2 intercourse encounters within the last 3 months)

You may not qualify if:

• Confirmed HIV-positive test result and/or signs and symptoms of an acute HIV infection
• Unknown or indeterminate HIV-1 status at screening or enrolment.
• Suspected or known serious infection(s), such as active tuberculosis
• Severe hepatic impairment or renal disease
• Allergy or hypersensitivity to any of the PrEP agents
• Known chronic Hepatitis B infection and currently taking oral PrEP
• Use of contraindicated medications for LEN: ergot derivatives (ergotamine, ergonovine, dihydroergotamine, methylergonovine, ergometrine), and certain anticonvulsants.
• Concomitant Use of known enzyme-inducing or contraindicated medications including: rifampicin, rifapentine, phenytoin, phenobarbital, carbamazepine and oxcarbazepine.
• Do not spend a reasonable amount of time in the study area as residents, for school, or work, or are otherwise unable to participate in study visits for geographical reasons, according to the site investigator
• Medical, social or other condition that, in the opinion of the site investigator, would interfere with the conduct of the study or safety of the participant (e.g., provided by self-report, or found upon medical history and examination or in available medical records)
• Current enrolment in another interventional research study that in the opinion of the site investigator, would interfere with the conduct of the study or safety of the participant (as verified by registration on the South African Medical Research Council (SAMRC) biometric co-enrolment prevention system (BCEPS)).

Sponsors & Collaborators

• Desmond Tutu HIV Foundation: lead
• Bill and Melinda Gates Foundation: collaborator
• Gilead Sciences: collaborator
• ViiV Healthcare: collaborator

Study Sites (1)

DTHF Mobile Clinics

Cape Town, WC, 7925, South Africa

Location

Biospecimen

Retention: SAMPLES WITH DNA

Blood and dried blood spots.

MeSH Terms

Interventions

lenacapavir; cabotegravir; Tablets

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 29, 2026
• First Posted: February 5, 2026
• Study Start: January 29, 2026
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): May 1, 2028
• Last Updated: February 5, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Protocol will be made available in the form of a published protocol paper. High-level, de-identified operational data on PrEP use patterns will be shared with the National Department of Health on monthly basis from first enrollment to end of study in March 2028.
• Access Criteria: PI and co-Is at each site will control all rights to the data and intellectual property obtained from this project. To ensure confidentiality, data shared with project team members will be blinded (i.e. delinked from identifying participant information). All data transferred between investigators will be done securely through password-protected files. High-level, de-identified operational data on PrEP use patterns will be shared with the National Department of Health as per the national reporting stationary. All pregnancies amongst participants using LEN, CAB LA or TDF/FTC and occurring during the study, along with their outcome, will be recorded and reported to SAHPRA, UCT HREC as well as the study's collaborating partners (Gilead Sciences in the case of pregnancy while using LEN) irrespective of their association with an AE or SAE. The pregnancies will be registered on the Gilead Sciences Patient Safety Database and Viiv Healthcare/ GSK.

Locations

ZA (1)