Post-Injectable Cabotegravir Antiretroviral Salvage Strategy Options Trial
Co-National Principal Investigators
Dr Simiso Sokhela (MBChB)
Director: Clinical Research, Ezintsha, Wits Health Consortium University of the Witwatersrand
Building C
Sunnyside Office Park
32 Princess of Wales Terrace
Parktown, Johannesburg 2193
South Africa
Dr Mark Siedner MD MPH Clinical Faculty
Africa Health Research Institute KwaZulu-Natal, South Africa Associate Professor of Medicine Harvard Medical School
Boston, Massachusetts, United States
Co-ordinating Investigator
Dr Simiso Sokhela
Director: Clinical Researcher, Ezintsha, Wits Health Consortium University of the Witwatersrand
Ezintsha Clinical Research Site
Building C, Sunnyside Office Park
32 Princess of Wales Terrace
Parktown, Johannesburg 2193
South Africa
Study Design
PICASSO will be a two-phase interventional study to identify the optimally safe and effective ART regimen for individuals with newly detected HIV infection after recent CAB-LA PrEP exposure.
This study will use a single-arm interventional design to determine the epidemiology of INSTI resistance and efficacy of a standardised ARV treatment regimen (i.e., TLD) in individuals with HIV-1 infection and recent CAB-LA PrEP exposure across multiple sites in South Africa.
Population
Men and women ≥ 15 years of age with newly diagnosed HIV-1 infection and recent CAB-LA PrEP exposure (i.e., within the past twelve months) will be enrolled.
The following eligibility criteria will be used to select study participants.
Inclusion Criteria: Each participant must meet all of the following criteria to be enrolled in this study:
- Male or female.
- Age ≥ 15 years, inclusive, at the time of signing the informed consent.
- Body weight ≥ 35 kg.
- Confirmed HIV-1 infection.
- Exposure to at least one dose of CAB-LA PrEP in the past 12 months.
- Consent to initiation of ART.
- Estimated glomerular filtration rate (eGFR) > 50 min/mL
Exclusion Criteria: Participants meeting any of the following criteria will be excluded from the study:
- Any previous exposure to DTG.
- 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.
- Known hypersensitivity or specific contraindications to the use of any of the active drugs in the treatment arms or similar compounds.
- 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:
- tuberculosis therapy (i.e., rifampicin, rifapentine, rifabutin), with the exception of isoniazid (INH) prevention therapy;
- anti-convulsants (e.g., carbamazepine, oxcarbazepine, phenobarbital, phenytoin);
- herbal products (e.g., St John’s Wort).
- 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.
- 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.
Drug Intervention
Tenofovir disoproxil fumarate/lamivudine/dolutegravir (TLD)
Objectives and Endpoints (Phase 1)
Primary Objective
- 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
Primary Endpoint
- Proportion of participants with virologic suppression (plasma HIV-1 RNA levels < 50 cp/mL) at Month 6
Secondary Objectives
- 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.
- To evaluate the development of HIV drug resistance over 12 months of HIV treatment with TLD
- To evaluate the safety of TLD over 12 months in individuals with prior CAB- LA exposure
Secondary Endpoints
- Proportion of participants with unsuppressed viral loads (HIV-1 RNA levels ≥ 50 cp/mL and ≥ 1000 cp/mL) at Month 6 and Month 12
- Time to virologic suppression
- Prevalence of HIV genotypic resistance to NRTI and INSTI drug classes at screening (baseline)
- 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
- 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
- Incidence of serious adverse events (SAEs) and DAIDS-defined Grade 3 and Grade 4 adverse events (AEs), throughout study duration, including AEs considered related to the IMP
- Proportion of participants discontinuing treatment due to AEs
- Assessment of absolute values and changes in laboratory parameters over 12 months
Exploratory Objectives
- To evaluate the effects of IMP on metabolic health over 12 months
Exploratory Endpoints
- Changes from baseline in BMI, lipids and glycated haemoglobin (HbA1C) throughout the study
Sample Size
Maximum 100 participants
Follow Up
12 months (excluding screening) per participant
