Clinical trial NCT06485154: Post-Injectable Cabotegravir Antiretroviral Salvage Strategy Options Trial
Official title: Post-Injectable Cabotegravir Antiretroviral Salvage Strategy Options Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: HIV Prevention
Keywords: Pre-Exposure Prophylaxis (PrEP)
Antiretroviral therapy
Tenofovir Disoproxil Fumarate/Lamivudine/Dolutegravir
Lead sponsor: University of Witwatersrand, South Africa
Sponsor class: OTHER
Collaborators: name: Bill and Melinda Gates Foundation
First posted: 2024-07-03
Enrollment: 100
Sex: ALL
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Oral - 1 tablet (300/300/50 mg TDF/3TC/DTG) daily
Primary purpose: PREVENTION

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: At 6 Months
Secondary outcomes:
measure: 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
timeFrame: 6 and 12 Months
measure: 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
timeFrame: 12 Months
measure: 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
timeFrame: 12 Months
measure: 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
timeFrame: 12 Months
measure: To investigate the development of HIV drug resistance over the duration of the trial of HIV treatment with TLD
timeFrame: 12 Months
measure: To evaluate the safety of TLD over 12 months
timeFrame: 12 Months
measure: To evaluate the safety of TLD over 12 months
timeFrame: 12 Months
measure: To evaluate the safety of TLD over 12 months
timeFrame: 12 Months
Other outcomes:
measure: To conduct investigation on the effects of IMP on metabolic health over 12 months
timeFrame: 12 Months
measure: To conduct investigation on the effects of IMP on metabolic health over 12 months
timeFrame: 12 Months
measure: To conduct investigation on the effects of IMP on metabolic health over 12 months
timeFrame: 12 Months
Locations:
city: Johannesburg
country: South Africa
facility: Ezintsha, a division of Wits Health Consortium
state: Gauteng
city: Durban
country: South Africa
facility: Africa Health Research Institute (AHRI)
state: KwaZulu-Natal
city: Cape Town
country: South Africa
facility: Desmond Tutu Health Foundation
state: Western Cape
Study officials:
affiliation: Ezintsha, a division of Wits Health Consortium
name: FRANCOIS WD VENTER, PhD
role: STUDY_DIRECTOR
References: