CARES

Cabotegravir And Rilpivirine: Efficacy and Safety Study

About Us

Cabotegravir And Rilpivirine: Efficacy and Safety Study

Background to the study

Since its discovery in the early 1980’s the HIV/AIDS pandemic has gone on to affect over 37 million people globally; it has especially affected the people in poor countries including Uganda. In Uganda, HIV/AIDS is thought to affect over 1.3Million people and almost an equal number are on .HIV treatment

HIV treatment, now commonly known as Antiviral therapy (ART) has been in use since the first drug Zidovine (AZT) was discovered in 1987. Improvements in the treatment have aimed at improving drug effectiveness through combining drugs and the current regimes commonly contain three drugs. These combinations however, frequently result into side effects from the drugs and numerous the numerous pills cause pill burden. Subsequent efforts from 2020 therefore have aimed at reducing 1) number of pills taken per day, 2) the number of drugs in the combinations in order to reduce pill burden and 3) the amount of side effects; a process called simplification.

Further simplification has led to the development of long acting depot injections, the first of which was recently approved/licensed in 2020 containing two-drug combination of Cabotegravir (CAB) and Rilpivirine (RPV).

The studies that led to this licensing were mostly done in Europe, the Americas and Asia whose populations and socioeconomic backgrounds significantly differ from African populations

The studies therefore tended to have more Caucasians, more males proportionately, and significantly better health systems. Additionally the trial setting was overly regulated with intense laboratory testing which is not the case in the public health sector in Africa. The findings therefore, although positive, cannot be generalized to a public health setting in Africa. Several issues have been raised;

  • Can the public health system adopt with less frequent monitoring especially for viral loads that are required to see if medicine is still working?
  • Will this treatment work where there is a possibility of background resistance to ART?
  • Can injections be safely delivered?
  • Can the cold chain that is required for Rilpivirine be managed well?
  • Will the participants be able to return on time for their treatment?
  • What is the preference for the African population?

This study therefore sets out to answer these questions. Through funding from Janssen EMEA and drug donations from both manufactures of Cabotegravir ((Viiv/GSK) and Rilpivirine (Janssen), a multi national clinical trial, coordinated by the JCRC has been set up.

The overall aim of this study is to determine/demonstrate that switching from taking daily ART pills to injectable long acting RPV +CAB will not reduce the effectiveness of the ART on the participants. This will mean that the viral control will be maintained, and the side effects will not be more and the general livelihood of the patient will not be affected.

How will the study be?

A target of 512 participants, who are already stable on their ART, will be enrolled in this study and randomized 1:1 to continue cART or switch to the RPV LA+CAB LA for a treatment period of 24 months. Participants will be recruited across 8 sites from 3 countries:

  1. 3 in Uganda namely Joint Clinical Research Centre (Kampala and Fort portal) and Infectious diseases institute
  2. 3 in Kenya (KEMRI, AMPATH and Aga Khan Hospital)
  3. 2 In South Africa (Ezintsha and SAMRC)

cART Group: Participants will continue on their normal ART as a single tablet or Fixed-Dose Combination regimen as per local country guidelines up to Month 24. Participants will be permitted to switch cART drugs in case of toxicity or for treatment optimization and convenience after viral load testing.

RPV LA+CAB LA Group: The participants will be given an option of staring with the oral form of RPV and CAB to see if they can take them well or to go straight to injections. After starting and stabilizing on injections, they will be returning for repeat injections every 2 months upto 24 months

Results

We will monitor the participants’ viral loads every six months to determine if they are responding well to treatment. In addition, we shall be monitoring for side effects very closely to see that the drugs are safe. Quality of life assessments, satisfaction with treatment as well as economic evaluations shall be done and reported at the end of the study as well

How will the study impact?

This is a topical study and of interest to the WHO. Results from this will inform ART policy especially for Africa

What we do

Who is Eligible to Participate in the CARES Trial?

A target of 512 participants, will be enrolled in this study and randomized 1:1 to either continue on their ART or switch to the intervention for a treatment period of 24 months. Eligible participants must meet the following criteria: