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CARES Study Impact in Canada
A CARES Package in Canada? Lessons From Africa on Long-Acting Cabotegravir Plus Rilpivirine

Released: April 02, 2024

Expiration: April 01, 2025

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Key Takeaways
  • Even when used with less frequent HIV-1 RNA monitoring in the CARES study, long-acting LA CAB + RPV demonstrated noninferiority and increased treatment satisfaction compared with standard oral ART.
  • LA CAB + RPV was effective in an area with a relatively high proportion of previous NNRTI exposure and NNRTI and INSTI resistance.

Injectable long-acting cabotegravir plus rilpivirine (LA CAB + RPV) is approved for the management of HIV by Health Canada, the European Medicines Agency, and the FDA in people who are 12 years of age and older, who weigh at least 35 kg, and who are virologically suppressed. After initiation, HIV-1 RNA typically is measured every 3-6 months. However, this frequency of HIV-1 RNA monitoring may be out of reach for some groups, particularly in resource-limited settings.

At CROI 2024, Kityo and colleagues shared results at 48 weeks from the CARES study. This was a randomized, open-label phase IIIb trial evaluating the efficacy and safety of switching to LA CAB + RPV every 8 weeks vs continuing maintenance with oral antiretroviral therapy (ART) among persons in Africa living with HIV who are stable on first-line ART. The investigators used a public health approach that entailed less frequent HIV-1 RNA monitoring every 24 weeks. 

The results were consistent with previous studies in that LA CAB + RPV demonstrated noninferiority to oral ART. Retention in the study was high (99%), with virologic success in 96.9% of participants on the LA CAB + RPV arm vs 97.3% on the oral ART arm (adjusted difference: -0.5%; 95% CI: -3.4% to 2.4%).

This was despite a relatively high rate of resistance; at baseline, 13.5% and 16.1% of all participants had RPV or CAB resistance mutations, respectively. Only 1 participant on the LA CAB + RPV arm had confirmed virologic failure, and they resuppressed after switching to dolutegravir/lamivudine/tenofovir disoproxil fumarate. 

Furthermore, few adverse events were reported, and most were grade 1-2 injection-site reactions. One adverse event led to treat discontinuation on the LA CAB + RPV arm.

Finally, treatment satisfaction was greater among those receiving LA CAB + RPV.

Implications for Real-world Practice in Canada
What makes the data from the CARES study so exciting is that the study was conducted in 3 countries in sub-Saharan Africa—Kenya, Uganda, and South Africa—and fills important knowledge gaps in a few key areas. 

First, it provides more data than previous clinical trials on the efficacy of this regimen among women (specifically Black African women) and among those with other HIV-1 subtypes (with more than one half of participants having subtype A-1).

Second, the study took place in settings in which there were high levels of NNRTI exposure (74%). Despite this, at 48 weeks, there was only 1 treatment failure. Although further data focusing on those with baseline resistance are needed, this may allay some of the earlier concerns about the use of this regimen among those with pretreatment resistance. 

Lastly, in many resource-limited settings, HIV-1 RNA monitoring is a barrier because of availability and cost. In this study, HIV-1 RNA monitoring was done every 24 weeks, thereby addressing some implementation concerns.

Taken together, these findings strengthen the role that LA CAB + RPV has as an effective treatment option for people living with HIV.

Although the study was conducted in Africa, there are lessons to be learned for Canadians. For me, the increased representation of women in the CARES study is important because in my setting, half of the patients I see are women. 

Although HIV-1 RNA testing is free in Canada, for some people living with HIV, particularly in more northern or remote areas, frequent clinic visits for testing can be a challenge.

I look forward to longer-term follow-up data on participants in the CARES study, particularly on virologic failure and resistance.

Your Thoughts?
Will data from the CARES study affect your practice when using LA CAB + RPV? Get involved in the conversation by posting a comment below.