CARES

Cabotegravir And Rilpivirine: Efficacy and Safety Study

The history of ART leading to the CARES trial

The CARES project summary

Primary objective:

  • To demonstrate the non-inferior antiviral activity of switching to IM RPV LA+CAB LA administered every 2 months compared with continuation of cART administered daily over 12 months in HIV-1 infected participants in a resource limited setting

Other objectives:

  1. To demonstrate the antiviral and immunologic activity of switching to IM CAB LA+RPV LA every 2 months compared to continuation of cART over 12 and 24 months of follow-up.
  2. To evaluate the safety and tolerability of switching to IM CAB LA+RPV LA every 2 months compared to continuation of cART.
  3. To assess viral resistance in participants experiencing protocol-defined confirmed virologic failure(plasma HIV-1 RNA ≥200 c/mL).
  4. To assess the incidence of on-treatment genotypic resistance to CAB, RPV and other on-study cART up to Month 12and 24.
  5. To evaluate adherence to treatment.
  6. To evaluate the effect of RPVLA+CAB LA on trunk fat compared with cART
  7. Retrospective analysis of archived resistance and virological outcomes using PBMCs at baseline.
  8. To assess preference for CAB LA+RPV LA compared to oral cART.
  9. To determine the prevalence of HBV DNA and anti-HBs positivity among participants on stable cART containing NRTI who test negative for HbsAg and positive for anti-HBc at screening.
  10. To assess participant satisfaction with the injectable intervention.

Methodology

CARES is a randomized, open-label, active-controlled, multicenter, interventional study in virologically suppressed (<50 c/mL) HIV-1 infected adult participants with a total follow up period of  24 months.

Main Inclusion and exclusion Criteria

Eligible participants  stable on first-line cART containing 2 nucleoside reverse transcriptase inhibitor (NRTIs; tenofovir [TDF] plus either lamivudine [3TC] or emtricitabine [FTC]) plus an INI (dolutegravir [DTG]) or a non-nucleoside reverse transcriptase inhibitor (NNRTI) (efavirenz [EFV] or nevirapine [NVP]) were randomised to either of two arms

  1. Standard of Care arm: Continuation of first-line cART
  2. LA group: Switching to begin therapy with CAB LA+RPV LA administered every 2 months. Participants randomized to the CAB LA+RPV LA group were given the option of a 4-week Oral Lead-in (OLI) Phase with oral CAB and oral RPV, or to directly receive the injectable CAB LA+RPV LA. This decision to dose with or without an OLI Phase was determined by the study participant following informed consent discussions with the investigator.

 

Enrolment

1039 participants were screened to enrol the targeted 512 participants across 8 sites from 3 countries (3 sites in Uganda, 3 sites in Kenya and 2 sites in South Africa).

Screen failures due to history of exposure to Hepatitis B virus (HBV) with no evidence of active disease were further tested for immunity against HBV

Expected Outcomes

Because the  CAB LA+RPV LA regimen offers the benefit of reduced dosing from daily pills to IM injections every 2 months, the study is expected to demonstrate whether or not this could have a positive impact on the patient’s quality-of-life. Furthermore, the study also aims to show whether or not this has the potential to improve adherence to treatment,  improve engagement in care and reduce the stigma associated with the daily use of oral pills.

The CARES study also aims to investigate whether CAB LA+RPV LA administered every 2 months is non-inferior to SOC in resource limited settings, where the majority of the population affected by HIV-1 consists of black African women, and where access to regular clinical and laboratory monitoring is more challenging.

In the course of screening, we eliminated almost half of all participants due to exposure to Hepatitis B despite having a negative HBsAg. We aim to investigate the best approach to screening for this TDF and 3TC/FTC sparing regimen in a public health setting 

Furthermore, in most Sub-Saharan Africa (SSA) countries, resistance to NNRTIs has reached levels greater than 10% (WHO HIV Drug Resistance Report, 2017), which has necessitated a switch to INI-based regimens for durable virologic control.

This study also aims to bridge other data gaps specific to SSA including choice for OLI and the lived experiences on CAB LA+RPV LA

Finally , the economic evaluation will support the policy recommendations from the CARES trial

Overall, the trial is expected to inform future policy on the use of CAB LA+RPV LA especially in public health settings in SSA