HIV Prevention
Conditions
Keywords
Pre-Exposure Prophylaxis (PrEP), Antiretroviral therapy, Tenofovir Disoproxil Fumarate/Lamivudine/Dolutegravir
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.
Interventions
DRUGTLD - Tenofovir Disoproxil Fumarate / Lamivudine / Dolutegravir
Dolutegravir, lamivudine and tenofovir disoproxil fumarate tablets, a combination of dolutegravir (integrase strand transfer inhibitor \[INSTI\]), lamivudine, and tenofovir disoproxil fumarate (both nucleoside reverse transcriptase inhibitors), is indicated as a complete regimen for the treatment of HIV-1 infection in adults and pediatric patients weighing at least 35 kg
Sponsors
University of Witwatersrand, South Africa
Bill and Melinda Gates Foundation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Masking description
Age ≥ 15 years, inclusive, at the time of signing the informed consent.
Intervention model description
Oral - 1 tablet (300/300/50 mg TDF/3TC/DTG) daily
Eligibility
Sex/Gender
ALL
Age
15 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | 6 and 12 Months | Proportion of participants with unsuppressed viral loads (HIV-1 RNA levels ≥ 50 cp/mL and ≥ 1000 cp/mL) at Month 6 and Month 12 |
| 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 evaluate the safety of TLD over 12 months | 12 Months | Incidence of SAEs and DAIDS-defined Grade 3 and Grade 4 AEs, throughout study duration, including AEs considered related to the IMP |
Countries
South Africa
Contacts
CONTACTBUKANI X DYARIWE
CONTACTSIMISO M SOKHELA, MBChB
STUDY_DIRECTORFRANCOIS WD VENTER, PhD
Ezintsha, a division of Wits Health Consortium
Outcome results
None listed