Ugandan scientists start trials on monthly HIV prevention pill

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Ugandan scientists are testing a new once-a-month pill to prevent HIV, a development that could further expand the growth of prevention options beyond daily tablets and long-acting injections.

The experimental drug currently in early-stage trials in Uganda, Kenya, and South Africa is designed to simplify HIV prevention by reducing how often people need to take medication.

Leading the Ugandan team trials is Dr Flavia Kiweewa Matovu, who was the champion of the Lenacapavir, the six-month prevention injection that was launched on April 17. In an exclusive interview, Dr Kiweewa noted that the idea is straightforward, where instead of remembering a pill every day, users would only need to take one dose each month.

“If you have a pill, you can take it once a month, you just remember a date like the first or the last day of the month, and that’s it. You don’t need frequent visits to a health facility like with injections, and you avoid the burden of carrying daily pill bottles,” Dr Kiweewa, the lead investigator, explained in an interview.

A shift from daily pills and injections

The monthly pill is part of a broader shift in HIV prevention, where scientists are trying to make options easier, more discreet, and better suited to people’s lives.

Currently, many people rely on daily oral pre-exposure prophylaxis (PrEP), while others are beginning to access long-acting injectable drugs such as lenacapavir, which can offer protection for up to six months.

Dr Kiweewa noted that PrEO needs adherence, but each method comes with challenges.

Daily pills require strict adherence, and missed doses can reduce effectiveness. Injectable options, while longer-lasting, require clinic visits and trained health workers. The monthly pill aims to sit in between, offering convenience without the need for injections.

“It’s very small, almost like an aspirin. Someone can easily carry it without attracting attention. That also helps reduce stigma, because it doesn’t look like a typical HIV drug," Dr Kiweewa said.

The adherence question

Despite its promise, Dr Kiweewa said the success of the monthly pill will depend on one key factor: whether people actually take it. That challenge is already well documented with daily PrEP, where missed doses have limited real-world impact despite high efficacy in clinical trials.

“If participants take it as prescribed, we expect it should work very, very well," Dr Kiweewa said.

The study is currently in the recruitment phase, with scientists enrolling participants across the three countries. Unlike trials for injectable drugs, where adherence can be confirmed during clinic visits, the monthly pill relies more heavily on self-administration.

This means researchers may need larger study populations and longer follow-up periods to determine effectiveness.

“If adherence is high, we could see results in about a year or two. If not, it may take longer,” she said.

“All these drugs work very well, close to 100 per cent if taken correctly. The difference is adherence. The medicine cannot work if you don’t take it,” Dr Kiweewa noted.

She noted that with a monthly pill, adherence could improve or worsen.

On one hand, fewer doses may make it easier for users to stay on track. On the other hand, missing a single pill could mean losing protection for an entire month. To address this, researchers are investing heavily in counselling and follow-up support for participants in the trial, many of whom are women at higher risk of HIV infection.

The drug is being developed by Merck & Co. (known as MSD outside the United States) with support from the Bill & Melinda Gates Foundation.

Expanding prevention choices

Flavia Kyomukama, Executive Director National Forum of People Living with HIV/AIDS Networks Uganda (NAFOPHANU), said the monthly pill reflects a growing recognition that no single HIV prevention method works for everyone. She noted that some people prefer injections that they can forget about for months. Others are uncomfortable with needles. Still others want options that are private and easy to carry.

“The future of HIV prevention is choice. Different people need different options that fit their lives,” Kyomukama said.

Uganda has a range of HIV pre-exposure prophylaxis (PrEP) options, including daily oral pills, the Dapivirine Vaginal Ring (DVR), long-acting injectable cabotegravir (CAB-LA), and the recently launched twice-yearly lenacapavir injection. These prevention methods are provided free of charge at designated government and partner health facilities for individuals at high risk of HIV infection.

As of late 2025, Uganda has made significant progress against HIV, reducing annual AIDS-related deaths by 64% (from 56,000 in 2010 to 20,000 in 2024) and new infections to 37,000, according to the Uganda AIDS Commission. While close to UNAIDS' 95-95-95 targets, challenges remain with over 1.4 million people living with HIV and high new infections among youth, with new cases reported in Mbarara in 2025.