Experimental HIV prevention drug shows rare infections

Medical researchers have reported rare cases of HIV infections among people using a powerful new prevention drug, Lenacapavir, during discussions at the Conference on Retroviruses and Opportunistic Infections (CROI) held in Denver in 2026.

Marketed under the brand name Yeztugo, the long-acting injectable medication has been hailed as one of the most effective tools yet developed to prevent HIV/AIDS. The drug is administered only twice a year, making it a convenient alternative to daily oral pre-exposure prophylaxis (PrEP) pills.

However, researchers at the conference presented new findings from two large clinical trials — PURPOSE I and PURPOSE II — showing that a small number of people contracted HIV despite receiving their injections exactly as prescribed.

The studies still showed extremely high protection levels.

The PURPOSE I trial followed more than 5 300 cisgender adolescent girls and young women in sub-Saharan Africa. Among more than 2 000 participants who received Lenacapavir injections, only two became HIV positive. In comparison, 77 infections occurred among participants taking daily oral PrEP.

The PURPOSE II trial involved over 3 000 men who have sex with men and gender-diverse individuals. In that group, three infections were recorded among those taking Lenacapavir, compared with 12 in the daily pill group.

Researchers calculated the infection rate for Lenacapavir users at roughly 0.07 to 0.11 cases per 100 person-years — an extremely low figure in HIV prevention studies.

Scientists are now investigating what they call "breakthrough infections," cases where a person becomes infected despite adhering perfectly to the treatment schedule.

Four individuals in the trials tested positive for HIV even though they had attended all appointments, received injections on time and had the expected levels of the drug in their blood.

Researchers from Gilead Sciences, the manufacturer of Lenacapavir, said they are still analysing the data to understand the cause.

Stephanie Cox of the company told delegates that so far, "nothing is obvious or easy to understand" about why the infections occurred.

Scientists also raised concerns about the possibility of drug resistance.

When HIV manages to replicate in the presence of a powerful drug, it can mutate and become less sensitive to that medication. Researchers found that four of the five participants who eventually tested positive developed resistance mutations in the virus.

This means the strain of HIV they carry may be less responsive to Lenacapavir and potentially similar drugs.

Despite this, experts stressed that such cases remain extremely rare.

Hyman Scott, medical director at the San Francisco AIDS Foundation, said the findings should not discourage people from using PrEP.

"The breakthrough infections are important to evaluate, but are extremely rare among the thousands of study participants," Scott said.

Experts emphasised that no medication is 100 percent effective for every person, but a protection rate close to 99 percent remains a major achievement in the fight against HIV.

Researchers are now examining possible biological factors such as differences in how the body absorbs the drug or how individual immune systems respond to infection.

Cost, however, remains a major barrier. In the United States, the treatment costs more than US$28 000 per year, raising concerns about global access.

Despite these challenges, several African countries have begun introducing the drug.

Zimbabwe, South Africa, Zambia and Malawi launched programmes using the injectable PrEP in February 2026.

Zimbabwe officially rolled out a pilot programme on February 19 in Epworth, making it one of the first countries globally to introduce the new HIV prevention method.

The programme is being supported by the President's Emergency Plan for AIDS Relief (PEPFAR) and the Global Fund to Fight AIDS, Tuberculosis and Malaria, which funded an initial supply of about 46 000 doses.

Authorities say the rollout will initially focus on 24 high-risk locations identified through epidemiological "hot-mapping".

The programme targets groups most vulnerable to HIV infection, including adolescent girls and young women, sex workers and pregnant or breastfeeding women.

Zimbabwe's Health Minister Douglas Mombeshora said the twice-yearly injection offers privacy and convenience that daily pills often fail to provide.

"For prevention to work, it must fit into real life," he said, noting that the six-month dosing schedule makes adherence much easier.

Health experts say that despite the rare breakthrough cases, PrEP — whether taken as daily pills or long-acting injections — remains one of the most effective ways to prevent HIV infection.