HIV Prevention Progress in Sub-Saharan Africa

Accelerating Efforts Amid Funding Shifts

Multiple HIV prevention initiatives are underway in sub-Saharan Africa, including the relaunch of a scaled-back vaccine trial in South Africa and the rollout of a new long-acting injectable drug, lenacapavir, in several countries.

BRILLIANT HIV Vaccine Trial in South Africa

The BRILLIANT Consortium, an African-led initiative, originally secured a $45 million grant from the U.S. Agency for International Development (USAID) in 2023 to develop an HIV vaccine. A meeting in Zanzibar in early 2025 involving numerous researchers and clinicians established plans for upcoming vaccine trials.

On January 20, 2025, a U.S. executive order froze foreign aid pending review, leading to reductions in USAID programs. The BRILLIANT Consortium subsequently received stop-work orders, suspending the trials before participant enrollment was scheduled to begin.

After the grant cancellation, researchers in South Africa created an alternative plan, scaling the initiative to focus solely on South Africa. The project secured funding from the South African Medical Research Council and the Gates Foundation. This new funding is approximately one-twentieth of the original USAID grant. No funding for the revised project was provided by the U.S. government.

After nearly a year of delays, participant screening for the scaled-down trials has commenced. The research is being conducted in Philippi Village, a township in Cape Town. The first vaccine injections for new trial participants are scheduled for the following week.

Lenacapavir Rollout

Several countries in southern Africa are implementing lenacapavir, a capsid inhibitor drug administered via injection every six months for HIV prevention. Clinical studies have indicated a high level of effectiveness.

South Africa

South African President Cyril Ramaphosa announced a R1.3 billion initiative to distribute lenacapavir. The rollout targets 360 public health clinics across 24 high-burden districts, aiming to reach approximately one million people by the end of 2027. Funding comes from the South African government, The Global Fund, and the Children's Investment Fund Foundation (CIFF).

South Africa has approximately 8 million people living with HIV and reports around 160,000 new infections annually, the highest number of any country globally. Initial doses provided by the Global Fund are sufficient for about 456,000 people over two years. A voluntary licensing agreement is expected to enable generic production by 2027. South Africa is exploring local manufacturing to reduce reliance on external supply.

Zimbabwe

Zimbabwe has initiated a donor-supported rollout of lenacapavir, targeting high-risk populations including young women, sex workers, adolescent girls, gay men, and pregnant and breastfeeding women. The rollout is supported by the United States President's Emergency Plan for AIDS Relief (PEPFAR) and the Global Fund. Approximately 46,000 individuals across 24 sites are projected to benefit during the initial phase. The Zimbabwean government has indicated it hopes to acquire its own doses for a broader rollout.

Eswatini

"Eswatini has the highest HIV prevalence globally," reporting approximately 4,000 new HIV infections annually among its 1.2 million population.

The country is rolling out lenacapavir, with initial doses provided by international donors.

Supply and Distribution

The rollout faces supply and distribution challenges. The Lobamba clinic received 130 doses and had administered over 100. The central medical store holds 730 doses, with 500 reserved for second injections. As of March 19, 2025, 2,995 individuals in Eswatini had initiated lenacapavir treatment. The Global Fund is supplying 6,000 doses for 2026, with 4,200 already delivered. An additional shipment funded by the U.S. government is anticipated later in the year. Health officials have stated the current quantity is insufficient for widespread prevention despite high public interest.

Target Populations

Priority groups for lenacapavir in Eswatini include teenage girls, young women, pregnant and breastfeeding mothers, and sex workers. Government guidelines recommend against denying requests for the drug to prevent stigmatization. Other high-risk groups, including men who have sex with men, transgender women, and people who inject drugs, have experienced reduced access to specialized services following U.S. aid cuts. Some individuals in these groups have reported stigma when seeking care at mainstream health facilities.

Adherence to Existing Prevention Methods

Previous pre-exposure prophylaxis (PrEP) methods, including daily oral pills, vaginal rings, and the bi-monthly injectable Cab-LA, have presented adherence challenges. Some individuals have reported difficulties maintaining daily pill schedules due to lifestyle factors. Some women have reported discomfort with vaginal rings, and some have described Cab-LA as painful.

Patient Experiences

• An individual identified as Precious, a 32-year-old sex worker in Eswatini, tested negative for HIV and received lenacapavir. The treatment involved a loading dose of four pills and two injections. She reported that sex work was her primary source of income following domestic violence and a lack of formal qualifications.
• An individual identified as Princess, 27, sought lenacapavir at a clinic in Eswatini. Because she had had unprotected sex within the previous 72 hours, she was provided with a one-month supply of post-exposure prophylaxis (PEP) pills instead.

Pricing and Manufacturing

In the United States, lenacapavir costs $28,218 per patient annually. Through agreements with the Global Fund, lower-income countries pay approximately $60 per person per year.

Generic versions are projected to become available from 2027 at an estimated $40 per year, potentially dropping to $25 with increased demand. This is the first instance of an HIV drug becoming available in sub-Saharan Africa in the same year as higher-income countries. The manufacturer, Gilead Sciences, has faced criticism for restrictions on access to cheaper supplies and for not selling directly to humanitarian organizations.

U.S. and Global Distribution

The U.S. State Department and Global Fund are collaborating on a broader initiative to supply at least 2 million doses of lenacapavir to high-burden countries, primarily in Africa, by 2028. As of a recent announcement, initial doses of 500 each have been delivered to Eswatini and Zambia. Gilead Sciences CEO Daniel O'Day confirmed the company is supplying these initial doses at cost. Gilead has submitted applications for regulatory approval in Botswana, Kenya, Malawi, Namibia, Rwanda, Tanzania, Uganda, and Zimbabwe, with further applications planned. A senior U.S. official stated the U.S. does not plan to fund lenacapavir doses for South Africa, encouraging the country to fund its own supply.

Future Goals

Eswatini's Minister of Health, Mduduzi Matsebula, has stated the country aims to eliminate AIDS as a public health threat by 2030, with an internal target of 2028. The Eswatini government has indicated it is prepared to fund lenacapavir domestically.

Modeling for South Africa indicates that if one to two million HIV-negative individuals receive the injection by 2043, AIDS could cease to be a major public health problem in that country.