For the approximately 2.4 million children and adolescents living with HIV today, managing health is a lifelong commitment that has traditionally relied on a daily three-drug regimen. While adults have recently benefited from simpler two-drug treatments, the evidence for younger patients remained less certain, often leaving children behind in medical innovation. The D3/Penta 21 trial was launched to close this gap and provide a simpler, equally effective path for the next generation.
Researchers followed 386 children and adolescents across Uganda, South Africa, Thailand, Spain, and the UK. Recruitment took two years, but we’re still following these children today and will follow them through the rollover study to ensure they have access to the drug until it becomes available in their countries.
The results presented at CROI in February 2026, are full of hope: a two-drug regimen dolutegravir/ lamivudine (DTG/3TC) is just as effective as the standard three-drug approach at keeping the virus suppressed. Specifically, the rate of viral rebound was marginal when compared to the three-drug group. This means we can maintain good health while reducing the total amount of medicine a child must take over their lifetime.
Keeping children safe was the trial’s top priority. The study found that serious side effects were similar between both groups, proving that a simpler regimen does not come at the cost of a child’s well-being. Even in rare cases where virus levels rose slightly, most children in both groups successfully returned to suppressed levels by the end of the two years.
Moving to a two-drug treatment offers practical benefits that improve daily life for young children and their caregivers. The two-drug pills are smaller and easier to swallow than many traditional options. For the youngest children, the dispersible tablets are more palatable, which helps parents and caregivers administer medicine without the typical struggles. Beyond today’s convenience, this approach reduces a child’s long-term exposure to drugs, potentially lowering the risk of side effects as they grow.
The D3/Penta 21 trial provides the robust evidence needed to support DTG/3TC as a simple, effective option for children and adolescents who are already doing well on their current medication. This milestone ensures that children are no longer an afterthought in medical progress, but are instead receiving care that is efficient, affordable and comfortable.
The MRC Clinical Trials Unit at UCL has the Scientific Lead on the trial and a key role in trial operations management. They also contributed greatly to the regulatory submission coordinated by ViiV Healthcare.