None of 2,134 young women given an HIV prevention shot caught HIV, trial finds

For years, the main way to lower the chance of catching HIV with medicine has been a pill taken every day. Many people find it hard to remember a pill every morning, month after month. Two large trials have now tested a shot under the skin, given once about every six months instead [1][2].

In the first trial, none of the 2,134 teen girls and young women who got the shot caught HIV. Among 2,136 people on one daily pill, 39 did. Among 1,068 on another daily pill, 16 did [1].

The main caveat is about what the shot was measured against. Neither trial had a group that got no medicine, so the headline comparison was with an estimate of how many people would have caught HIV anyway. And outside the trials, the first real world report found delays in starting and some people stopping early [1][2][3].

HIV is a virus that attacks the body's defences against germs. Taking medicine before any contact with the virus, to stop an infection from starting, is called preexposure prophylaxis. The shot is called lenacapavir, and it is given every 26 weeks [1][2].

The first trial, PURPOSE 1, was led by Linda-Gail Bekker of the Desmond Tutu HIV Centre at the University of Cape Town. It was published in the New England Journal of Medicine in 2024 and took place in South Africa and Uganda. Chance decided, like a coin flip, who got the shot and who got one of two daily pills. Everyone also got a dummy shot or a dummy pill with no medicine in it, so nobody knew which group they were in [1].

The researchers put the result in one line:

No participants receiving twice-yearly lenacapavir acquired HIV infection.

In plain words, across the whole trial, nobody in the shot group caught HIV. Results that clean are rare in prevention trials. The paper also notes that many people did not take their daily pills as planned, which may explain part of the gap between the groups [1].

Did the second trial find the same thing?

The second trial, PURPOSE 2, was led by Colleen Kelley of the Hope Clinic of Emory University School of Medicine and published in the same journal. It tested the shot in cisgender men, transgender women and men, and gender nonbinary people in North America, South America, Africa and Asia [2].

Among 3,265 people, 2 in the shot group caught HIV, against 9 in the daily pill group. That works out to about 1 case for every 1,000 people followed for a year on the shot, against about 9 on the pill [2].

Both trials also compared the shot with an estimate of the local rate of new cases. They worked it out from everyone who was tested to see if they could join, and it came to about 2.4 cases per 100 people a year in both trials. That is a fair approach, because holding back pills that already work would be wrong. But the people tested to join are not the same people who joined, and the rate was calculated rather than seen [1][2].

Most side effects were where the shot went in. In the first trial, about 7 in 10 people on the shot had a reaction there, against about 1 in 3 who got a dummy shot. Four people stopped because of it. In the second trial, 26 of 2,183 people on the shot stopped for that reason, against 3 of 1,088 on the pill [1][2].

Both trials were paid for by Gilead Sciences, the company that makes the shot, and some of the authors work there. The papers say so openly, which is how it should be. It also means other teams need to repeat the work before the result counts as settled [1][2].

What happens outside a trial? A 2026 report in Clinical Infectious Diseases was led by Aniruddha Hazra of the University of Chicago. It followed the first 501 people to start the shot at 17 sites in the United States. Getting started was often slowed down by insurance steps [3].

Early non-persistence was uncommon (3.6%) but exceeded clinical trial discontinuation rates and was strongly associated with abdominal injections and injection-site reactions requiring clinical contact, underscoring modifiable clinical and structural barriers to early persistence.

In plain words, few people stopped early, about 4 in 100, but more than in the trials. Stopping was linked to shots given in the belly and to reactions that needed a visit to a doctor or nurse [3].

These trials do not show how well the shot works compared with no medicine at all. They do not show whether people keep coming back every six months for years. And because both chose people with a high chance of catching HIV, the rates may not carry over to other groups [1][2][3].

What they do show is clear within those limits. In two large trials, very few people given the shot caught HIV, and fewer did than on the daily pills [1][2].