Title: A Phase 3b, Randomized, Multicenter, Open-Label Study Evaluating the Efficacy, Safety, and Tolerability of Switching to Long-Acting Cabotegravir Plus Long-Acting Rilpivirine From Current Antiretroviral Regimen in HIV-1 Infected, Virological Suppressed Adults in Sub-Saharan Africa

Lay title: A study among virally suppressed adult infected with HIV-1 in sub-Sahara Africa. The study is evaluating 2 ARVs cabotegravir and rilpinavir which are long acting and are given intramuscularly. The development of innovative antiretroviral (ARV) compounds for the treatment of human immunodeficiency virus type 1 (HIV-1) should target drugs with high barrier to resistance, improved tolerability, safety and simplified fixed-dose combination (FDC) regimens.

 Currently, most patients infected with HIV-1 are treated with a combination of 3 or 4 drugs, including nucleo(t)side reverse transcriptase inhibitors (N[t]RTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs) and/or integrase inhibitors (INIs). Virologic suppression and treatment response in HIV-1 infected patients are primarily dependent on adherence to antiretroviral therapy (ART).

The pill burden of currently available treatments, dosing frequency, and safety concerns frequently contribute to non-compliance and the emergence of drug-resistant virus in resource limited setting. Long-acting (LA) injectable therapy for the treatment of Human Immunodeficiency Virus (HIV)-1 infection will reduce the number of times that one has to take their medication and an additional option to the currently available two-drug oral combinations. Injectable LA formulation of rilpivirine (RPV) for intramuscular (IM) injection in combination with parenteral LA formulation of the integrase inhibitor cabotegravir (CAB) may offer a better tolerability and resistance profile, as well as improved adherence and treatment satisfaction in virologically suppressed patients. These two drugs being investigated in this study were approved by FDA in the USA in January 2021 but have not yet been approved in Kenya.

 Eligible participants will be randomized 1:1 to either continue combined ART or to discontinue combined ART and begin therapy with RPV LA+CAB LA administered every 2 months. Globally, a target of 512 participants will be enrolled and will remain in the study for a period of 24 months. Participants will have blood and urine samples taken, with additional blood drawn for future testing. Kericho site will be enrolling up to 60 participants. This study is also carried out in Uganda and South Africa. In Kenya, two other sites will be participating. The primary endpoint will be to Proportion of participants with a virologic response (plasma HIV-1 RNA <50 c/mL) at Month 12.

The development of innovative antiretroviral (ARV) compounds for the treatment of human immunodeficiency virus type 1 (HIV-1) should target drugs with high barrier to resistance, improved tolerability, safety and simplified fixed-dose combination (FDC) regimens. Currently, most patients infected with HIV-1 are treated with a combination of 3 or 4 drugs, including nucleo(t)side reverse transcriptase inhibitors (N[t]RTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs) and/or integrase inhibitors (INIs). Virologic suppression and treatment response in HIV-1 infected patients are primarily dependent on adherence to antiretroviral therapy (ART). The pill burden of currently available treatments, dosing frequency, and safety concerns frequently contribute to non-compliance and the emergence of drug-resistant virus in resource limited setting. Long-acting (LA) injectable therapy for the treatment of Human Immunodeficiency Virus (HIV)-1 infection offers a reduced dosing frequency and an additional option to the currently available two-drug oral combinations. A parenteral LA formulation of rilpivirine (RPV) for intramuscular (IM) injection in combination with parenteral LA formulation of the integrase inhibitor cabotegravir (CAB) may offer a better tolerability and resistance profile, as well as improved adherence and treatment satisfaction in virologically suppressed patients. These drugs were approved by US FDA in January 2021 but have not been approved in Kenya.This phase 3b, randomized, multicenter, open-label study will be evaluating the efficacy, safety, and tolerability of switching to long-acting Cabotegravir plus long-acting rilpivirine (RPV LA+CAB LA) from current antiretroviral regimen in HIV-1 infected, virologically suppressed adults in Sub-Saharan Africa. Eligible participants will be randomized 1:1 to either continue combined ART or to discontinue combined ART and begin therapy with RPV LA+CAB LA administered every 2 months. Globally, a target of 512 participants will be enrolled and each participant will remain in the study for a period of 24 months. Participants will have blood and urine samples taken, with additional blood drawn for future testing. Kericho site will be enrolling up to 60 participants and with the anticipated screening: enrollment ratio of 2:1, Kericho will screen about 120 participants. The primary endpoint will be to Proportion of participants with a virologic response (plasma HIV-1 RNA <50 c/mL) at Month 12.