Post-Injectable Cabotegravir Antiretroviral Salvage Strategy Options Trial

Phase 4

Active, not recruiting

• Conditions: HIV Prevention
• Interventions: Drug: TLD - Tenofovir Disoproxil Fumarate / Lamivudine / Dolutegravir

• Registration Number: NCT06485154
• Lead Sponsor: University of Witwatersrand, South Africa

Brief Summary

This is a single-arm, open-label, effectiveness study designed to evaluate the use of Tenofovir, Lamivudine, and Dolutegravir in people with newly diagnosed HIV-1 infection initiating first-line Antiretroviral Therapy with Cabotegravir-Long-acting Pre-Exposure Prophylaxis exposure in the preceding 12 months. Participants will be followed up for a period of 12 months from enrolment.

Detailed Description

Study participants are HIV-1 infected adult patients recruited. A target of 100 participants will be enrolled and started on Tenofovir, Lamivudine, and Dolutegravir at enrolment. Clinical assessments for these participants will be conducted throughout the study as per the Schedule of Events.

This will be a two-phase interventional study to identify the optimally safe and effective Antiretroviral Therapy regimen for individuals with newly detected Human Immunodeficiency Virus infection after Cabotegravir-Long-acting Pre-Exposure Prophylaxis exposure. In the Initial Phase, the investigator will demonstrate proof of principle for the use of standardized Antiretroviral Therapy regimens in combination with pre-treatment genotypic drug resistance testing to achieve virologic suppression in individuals with prior Cabotegravir-Long-acting Pre-Exposure Prophylaxis exposure and understand drug resistance patterns prior to Antiretroviral Therapy initiation. To do this, the investigator will use a single-arm, interventional design using Tenofovir, Lamivudine, and dolutegravir. This supports programmatic rollout, particularly in developing countries where baseline Human Immunodeficiency Virus genotyping is not performed prior to initiation of Antiretroviral Therapy. The over-arching goals of Phase I are to determine the feasibility of our study design to recruit people with detectable Human Immunodeficiency Virus after prior use of Cabotegravir-Long-acting Pre-Exposure Prophylaxis failure and to estimate virologic suppression rates with current first-line standard of care, Tenofovir, Lamivudine, and Dolutegravir therapy.

At the conclusion of the Initial Phase, data will be assessed to determine the need for and optimal design of a potential Second Phase (the details of which will not be described in this protocol). Should the investigator find sub-optimal virologic suppression rates on Tenofovir, Lamivudine, and Dolutegravir regimens in this trial, the investigator would then proceed to the Second Phase in which the investigator will compare Darunavir/Ritonavir based Antiretroviral Therapy with Tenofovir, Lamivudine, and Dolutegravir in an open-label randomized, non-inferiority clinical trial. The aim of the second phase will be to determine whether an alternative to the predominant first-line regimen in much of the world will be required to optimise virologic suppression for this population.

Study Timeline

• Status Verified: 2024-06
• Study Start: 2024-06-01
• Study First Submitted: 2024-06-10
• Study First Submitted QC: 2024-06-26
• Last Update Submitted: 2024-06-26
• Study First Posted: 2024-07-03
• Last Update Posted: 2024-07-03
• Primary Completion: 2026-06-30
• Study Completion: 2026-08-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

1. Male or female.
2. Age ≥ 15 years, inclusive, at the time of signing the informed consent.
3. Body weight ≥ 35 kg.
4. Confirmed HIV-1 infection.
5. Exposure to at least one dose of CAB-LA PrEP in the past 12 months.
6. Consent to initiation of ART.
7. Estimated glomerular filtration rate (eGFR) > 50 min/mL

Exclusion Criteria

1. Any previous exposure to DTG.

2. Concurrent or recent (within the preceding 3 months) participation in another interventional clinical trial with a compound likely to interfere with any of the investigational medicinal products.

3. Known hypersensitivity or specific contraindications to the use of any of the active drugs in the treatment arms or similar compounds.

4. Is receiving or has received the following agents within 28 days prior to screening, and cannot discontinue their use for the duration of the study:

   1. tuberculosis therapy (i.e., rifampicin, rifapentine, rifabutin), with the exception of isoniazid (INH) prevention therapy;
   2. anti-convulsants (e.g., carbamazepine, oxcarbazepine, phenobarbital, phenytoin);
   3. herbal products (e.g., St John's Wort).

5. Any surgical or medical condition which may significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardize the safety of the volunteer or the objectives of the study or impair their ability to comply with the dosing schedule and/or protocol evaluations. The Investigator should make this determination in consideration of the volunteer's medical history.

6. Participant is judged by the Investigator to be at significant risk of failing to comply with the provisions of the protocol as to cause harm to self or seriously interfere with the validity of the study results. This including inability or an unwillingness to be followed up for the study period.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
TLD - Tenofovir Disoproxil Fumarate / Lamivudine / Dolutegravir	TLD - Tenofovir Disoproxil Fumarate / Lamivudine / Dolutegravir	The IMP is defined as any investigational marketed product to be administered to a study participant according to the study protocol. Participants will all receive TLD as detailed below. Treatment will be open-label, and drugs will be dispensed at intervals as specified in the Schedule of Events. Investigational Product Tenofovir disoproxil fumarate / lamivudine / dolutegravir Dosage Formulation 300 mg / 300 mg / 50 mg fixed dose combination tablet Route of Administration Oral Dosing Instructions 1 tablet (300/300/50 mg TDF/3TC/DTG) daily

Primary Outcome Measures

Name	Time	Method
To evaluate the efficacy of TLD as first-line antiretroviral therapy (ART) in participants with HIV-1 infection and CAB-LA PrEP exposure in the past 12 months	At 6 Months	Proportion of participants with virologic suppression (plasma HIV-1 RNA levels \< 50 cp/mL) at Month 6

Secondary Outcome Measures

Name	Time	Method
To evaluate the safety of TLD over 12 months	12 Months	Assessment of absolute values and changes in laboratory parameters over 12 months
To investigate the development of HIV drug resistance over the duration of the trial of HIV treatment with TLD	12 Months	Assessment of genotypic drug resistance in participants with confirmed virologic failure (HIV-1 RNA ≥ 200 cp/mL on 2 or more occasions) throughout study duration
To describe the epidemiology (i.e., prevalence and correlates) of HIV drug resistance patterns in participants with HIV-1 infection and prior CAB-LA PrEP exposure	12 Months	Comparative prevalence of INSTI drug resistance in those with HIV and CAB-LA exposure and HIV acquisition deemed to occur prior to initiation of PrEP, during PrEP therapy, or after cessation of therapy

Trial Locations

Locations (3)

Desmond Tutu Health Foundation; 🇿🇦 Cape Town, Western Cape, South Africa

Ezintsha, a division of Wits Health Consortium; 🇿🇦 Johannesburg, Gauteng, South Africa

Africa Health Research Institute (AHRI); 🇿🇦 Durban, KwaZulu-Natal, South Africa