A Game-Changer for HIV Treatment?

For decades, people living with HIV have had to take daily pills to keep the virus under control. Instead of a daily routine, what if they could receive an injection every two months?

A new study conducted in Africa suggests that long-acting injectable HIV treatment could be just as effective as daily pills—and might offer a new way forward in the fight against HIV.

Long-acting injectable therapy (LA) has become a recommended alternative to oral antiretroviral therapy (ART) for HIV-1 treatment in high-income countries. However, its role in treatment programs in Africa remained uncertain due to differences in demographic factors, viral characteristics, and healthcare infrastructure. To address this gap, the ongoing phase 3b randomized CARES trial was designed to evaluate the efficacy, safety, and tolerability of switching from oral ART to LA therapy in African settings.

The CARES trial, conducted across eight sites in Uganda, Kenya, and South Africa, studied whether long-acting injections of two drugs—cabotegravir (CAB) and rilpivirine (RPV)—could match the effectiveness of traditional daily oral antiretroviral therapy (ART).

A year ago, at the Conference on Retroviruses and Opportunistic Infections (CROI 2024), researchers presented the 48-week results, showing that the injectable treatment was non-inferior to daily pills. Now, at CROI 2025, new 96-week data confirms that long-acting injectables remain highly effective over time, reinforcing their potential as an alternative to daily ART in sub-Saharan Africa.

What the Study Found

The trial included 512 adults with HIV who had already achieved stable virus control on daily pills. They were randomly assigned to either continue with their oral medication or switch to the long-acting injection, which was administered intramuscularly every eight weeks.

After 96 weeks—almost two years—researchers found that 96.9% of people receiving the injections had successfully maintained very low levels of the virus in their blood (defined as <50 copies/mL). That figure was nearly identical to the 97.3% success rate in those taking daily pills. The study also confirmed non-inferiority, meaning the injectable treatment was not worse than the oral therapy within a predefined margin (−0.4%; 95% confidence interval: −3.1 to 2.0%).

These findings build upon the 48-week results, which also demonstrated comparable efficacy between injectables and daily ART. The long-term durability of this treatment approach suggests it could be integrated into HIV care programs with confidence.

Why this Matters

While daily pills have revolutionized HIV treatment over the years, they come with challenges. Some people struggle to take medication every day due to stigma, forgetfulness, or personal circumstances. Missing doses can increase the risk of the virus developing resistance to medication.

Long-acting injectables could provide a more convenient alternative, especially for people who have difficulty maintaining a daily pill routine. This could be particularly important in regions where access to consistent healthcare is a challenge.

Dr. Cissy Kityo, one of the lead researchers on the study, emphasized that the injections could be a “game-changer” for HIV treatment programs, particularly in Africa, where healthcare access varies and long-term adherence to daily pills can be difficult for many patients.

Are there Any Risks?

Like any medical treatment, the long-acting injection had some side effects. About 16% of participants receiving the injections experienced moderate to severe side effects, compared to 9% in the group taking oral pills. The most common issue was injection-site reactions, such as pain, swelling, or abscess formation, though these were generally mild to moderate in severity.

A small number of people on the injectable treatment—1.6%—experienced what’s known as confirmed virologic failure (CVF), meaning their virus levels increased beyond 200 copies/mL despite the treatment. However, three of these four participants were able to regain viral suppression after switching to a regimen of tenofovir disoproxil fumarate (TDF), lamivudine (3TC), and dolutegravir (DTG). Notably, baseline resistance mutations to rilpivirine were detected in 8% of participants, though these did not appear to significantly impact treatment success rates.

What’s Next?

The study’s findings suggest that long-acting injectable HIV treatment is a safe and effective alternative to daily pills. However, questions remain about how best to implement this approach in healthcare systems across Africa and beyond.

One challenge is ensuring that patients return for their injections every eight weeks. Unlike pills that can be taken at home, injectables require visits to a healthcare provider. Infrastructure improvements, expanded access to healthcare facilities and patient education, will be key to making this treatment widely accessible.

The potential benefits are significant. If scaled up, long-acting injections could reduce the burden of daily pill-taking, help overcome stigma, and improve overall HIV treatment outcomes.

As more studies confirm these findings, countries around the world may soon consider adding long-acting injectable therapy to their HIV treatment programs. For millions of people living with HIV, this could be a major step toward simpler, more effective care.