Post-Injectable Cabotegravir Antiretroviral Salvage Strategy Options Trial (PICASSO)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: HIV Prevention
• Intervention / Treatment: Drug: TLD - Tenofovir Disoproxil Fumarate / Lamivudine / Dolutegravir

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 Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 4

Contacts and Locations

Study Locations

• South Africa
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 2193
      • Ezintsha, a division of Wits Health Consortium
  • KwaZulu-Natal
    • Durban, KwaZulu-Natal, South Africa, 3935
      • Africa Health Research Institute (AHRI)
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7925
      • Desmond Tutu Health Foundation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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

Drug: TLD - 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; Other Names: Acriptega

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Proportion of participants with virologic suppression (plasma HIV-1 RNA levels < 50 cp/mL) at Month 6	At 6 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Proportion of participants with unsuppressed viral loads (HIV-1 RNA levels ≥ 50 cp/mL and ≥ 1000 cp/mL) at Month 6 and Month 12	6 and 12 Months
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	Time to virologic suppression	12 Months
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	Prevalence of HIV genotypic resistance to NRTI and INSTI drug classes at screening (baseline)	12 Months
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	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	12 Months
To investigate the development of HIV drug resistance over the duration of the trial of HIV treatment with TLD	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	12 Months
To evaluate the safety of TLD over 12 months	Incidence of SAEs and DAIDS-defined Grade 3 and Grade 4 AEs, throughout study duration, including AEs considered related to the IMP	12 Months
To evaluate the safety of TLD over 12 months	Proportion of participants discontinuing treatment due to AEs	12 Months
To evaluate the safety of TLD over 12 months	Assessment of absolute values and changes in laboratory parameters over 12 months	12 Months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
To conduct investigation on the effects of IMP on metabolic health over 12 months	Changes from baseline in BMI throughout the study	12 Months
To conduct investigation on the effects of IMP on metabolic health over 12 months	Changes from baseline in lipids throughout the study	12 Months
To conduct investigation on the effects of IMP on metabolic health over 12 months	Changes from baseline in HbA1C throughout the study	12 Months

Collaborators and Investigators

• Sponsor: University of Witwatersrand, South Africa
• Collaborators: Bill and Melinda Gates Foundation
• Investigators: Study Director: FRANCOIS WD VENTER, PhD, Ezintsha, a division of Wits Health Consortium

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2024
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): August 31, 2026

Study Registration Dates

• First Submitted: June 10, 2024
• First Submitted That Met QC Criteria: June 26, 2024
• First Posted (Actual): July 3, 2024

Study Record Updates

• Last Update Posted (Actual): July 3, 2024
• Last Update Submitted That Met QC Criteria: June 26, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Antiretroviral therapy; Pre-Exposure Prophylaxis (PrEP); Tenofovir Disoproxil Fumarate/Lamivudine/Dolutegravir
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; HIV Integrase Inhibitors; Integrase Inhibitors; Tenofovir; Lamivudine; Dolutegravir
• Other Study ID Numbers: EZ-BB-036

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data that will be shared is all of the individual participant data collected during the trial, after deidentification.
• IPD Sharing Time Frame: Immediately following publication
• IPD Sharing Access Criteria: Anyone who wishes to access the data
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No