Cabotegravir injection stalls despite strong trial results as cost and funding realities reshape prevention strategy
By Bunmi Yekini
As South Africa prepares to introduce a new twice-yearly HIV prevention injection later this year, an earlier breakthrough drug that once promised to transform the fight against the virus is quietly fading from the spotlight.
Health officials say the country will begin rolling out lenacapavir at about 360 government clinics in 2026, supported by donated doses from the Global Fund to Fight AIDS, Tuberculosis and Malaria. The long-acting injection, taken once every six months, is designed to prevent HIV infection in people who are HIV-negative.
But the launch comes as long-acting cabotegravir, an injectable prevention drug administered every two months and approved in South Africa in 2022, remains largely absent from the country’s public health system.
Both medicines belong to a class of antiretroviral drugs that can be used by HIV-negative people to prevent infection, a strategy known as pre-exposure prophylaxis, or PrEP. While antiretrovirals are commonly used to treat people living with HIV, PrEP uses the same medications to stop infection before it occurs.
Cabotegravir once appeared poised to reshape HIV prevention. Large international trials reported in 2020 showed the injection prevented significantly more HIV infections than the widely used daily prevention pill.
Researchers hailed the findings as a potential “gamechanger” for HIV prevention.
Yet translating scientific success into national programmes has proven difficult. Cabotegravir costs substantially more to deliver than newer alternatives, and a planned large-scale rollout in South Africa stalled amid funding uncertainty.
A modelling study estimated the drug would cost about $180 per person each year, roughly four times the projected price of generic lenacapavir.
“Cabotegravir proved that long-acting HIV prevention works,” said Mitchell Warren, executive director of HIV advocacy organisation Avac. “But the plans to scale it up never fully materialised, and that meant losing valuable time.”
The drug had briefly gained momentum in 2024 when the United States’ President’s Emergency Plan for AIDS Relief pledged to donate supplies to several African countries, with South Africa expected to receive the largest share.
But those plans faltered as funding uncertainties emerged, and the anticipated shipments never arrived.
Although South Africa’s medicines regulator approved cabotegravir for HIV prevention in December 2022, the drug was never added to the national essential medicines list, a key step required for government procurement. Officials cited the high price.
“The assessment hasn’t changed,” said Fikile Ndlovu, deputy director-general for HIV in the health department. “Ideally we would offer multiple options, but we have to work within our budget.”
Lenacapavir’s lower cost and easier manufacturing have shifted the focus of HIV prevention planning.
Through a Global Fund agreement with manufacturer Gilead Sciences, South Africa and other countries will initially pay about $60 per patient each year for the drug, allowing enough doses to protect roughly 500,000 people over two years.
The new injection has also generated significant scientific excitement. In clinical trials, lenacapavir delivered near-complete protection against HIV infection and was named the 2024 Breakthrough of the Year by the journal Science.
Despite its stalled rollout, cabotegravir left a lasting mark on HIV prevention research.
Trials involving thousands of participants across Africa and other regions showed the injection dramatically reduced infection rates compared with the daily prevention pill. In one study of more than 3,000 women in African countries with high HIV rates, only four infections occurred among those receiving the injection compared with 36 among those taking daily tablets.
Real-world pilot programmes in South African clinics also found many people preferred injectable prevention over pills.
“When we offered people a choice, about 75% chose the injection,” said Linda-Gail Bekker, head of the Desmond Tutu Health Foundation, referring to research conducted among young participants.
Those programmes also highlighted challenges in monitoring HIV prevention, which differs from lifelong treatment because people’s risk of infection can change over time.
“Prevention use is not linear,” said Saiqa Mullick, an implementation scientist at Wits RHI who led a pilot programme offering cabotegravir in selected government clinics. “People move in and out of risk, and our systems are still learning how to track that.”
While South Africa prepares its first lenacapavir rollout, some countries are exploring ways to offer multiple injectable options.
Zambia, one of the first nations to introduce cabotegravir in routine health services, plans to keep the two-monthly injection available while also introducing lenacapavir.
Researchers say such parallel rollouts could offer insights into how people choose between different HIV prevention methods.
Lenacapavir enters the country’s HIV programme with three advantages rarely aligned in public health: lower cost, fewer clinic visits and strong protection against infection, a combination that health officials hope could expand access to HIV prevention across the country.