Long-acting HIV injections edge closer to widespread use in SA, but barriers remain

Injections that provide months of protection at a time against HIV infection have been hailed by several leading experts as game changers with the potential to help end the HIV epidemic.

The two antiretroviral-containing injections leading the field are long-acting cabotegravir (CAB-LA) and lenacapavir. Both have been shown to effectively eliminate the risk of contracting HIV in large clinical trials. The main difference between the two shots is that CAB-LA provides two months of protection at a time, while lenacapavir provides six.

CAB-LA captured global attention in 2020 when pivotal trial results showed that the two-monthly injection was more effective than daily prevention pills in preventing HIV infection. Lenacapavir was thrust into the spotlight four years later in 2024 when two large trials demonstrated that the twice-yearly injection provided almost perfect protection against HIV.

There are still no clear plans for providing CAB-LA in South Africa’s public sector clinics, despite the four-year head start that it had on lenacapavir. By contrast, lenacapavir injections could be available in some select public sector clinics by April of next year, according to reporting by Bhekisisa.

How CAB-LA fell behind

In July 2022, the World Health Organization (WHO) recommended CAB-LA as a tool to prevent HIV and by December 2022 it was registered for use in South Africa.

In February 2023 though, South Africa’s National Essential Medicines Committee stated that it could not recommend the use of CAB-LA in the country because the medicine’s manufacturer, ViiV Healthcare, had yet to share how much it would charge for the shots.

It was only in late 2023 that ViiV provided pricing details for public sector procurement in certain low- and middle-income countries, including South Africa. That price was about R540 ($30) per dose or R3,240 ($180) per person per year, which the health department said was unaffordable for the country.

The price has since dropped slightly to around R2,880 ($160) per person per year, Mitchell Warren, from the US-based HIV advocacy organisation Avac, told Spotlight.

In 2024, the health department requested further details from ViiV on its CAB-LA pricing, but there is no indication that any progress has been made towards securing a lower price and enabling local procurement of CAB-LA for public sector facilities.

Khadija Jamaloodien, the top official for health products procurement in the national Department of Health, told Spotlight the department could not comment on whether there had been any developments towards local procurement of CAB-LA.

A spokesperson for ViiV told Spotlight: “We have not received any orders to date for CAB-LA for PrEP to supply to South Africa”. PrEP, or pre-exposure prophylaxis, refers to taking an injection to prevent HIV infection.

What about CAB-LA in the private sector?

For those using private healthcare in South Africa, CAB-LA also remains inaccessible. ViiV has not launched CAB-LA in the private sector or disclosed the price at which it will sell CAB-LA through private pharmacies.

ViiV did not respond to Spotlight’s questions regarding its plans and timelines for launching CAB-LA in the country’s private sector.

Pepfar steps in, but doesn’t deliver

After the health department balked at ViiV’s CAB-LA price for the public sector, the US President’s Emergency Plan for Aids Relief (Pepfar) announced plans to kickstart the rollout of CAB-LA in South Africa and some other African countries.

Pepfar pledged to buy CAB-LA from ViiV for donation to 10 African countries during 2024 and 2025. The largest donation of 231,000 CAB-LA doses was designated for South Africa.

While some of the Pepfar-donated stock began reaching countries before the Trump administration halted foreign aid on 20 January 2025, according to Warren, South Africa never received any of the promised doses.

These donations are no longer expected, given cuts to the agency’s capacity and budget under the Trump administration.

The US State Department did not respond to Spotlight’s questions seeking confirmation that the CAB-LA donations would no longer be delivered, but our health department told Spotlight it did not expect to receive this donation.

Gilead leapfrogs ViiV

Amid the delays and uncertainty surrounding CAB-LA’s pricing and rollout, Gilead, the company that manufactures lenacapavir, has positioned its product to become the first long-acting injectable form of HIV prevention available at any real scale in South Africa.

While lenacapavir is not yet registered in South Africa, Hasina Subedar, the senior technical advisor for HIV prevention in the national Department of Health, told Bhekisisa that it planned to start rolling out lenacapavir in 300 public clinics by April 2026 — less than 10% of the well over 3,000 clinics in the country.

SA Health Products Regulatory Authority authorisation is expected to be granted in the coming months, as lenacapavir has already been recommended for marketing authorisation through the EU medicines for all (EU-M4All) initiative — a process that includes regulators from South Africa. In addition to securing local registration, lenacapavir must also receive a positive recommendation from South Africa’s National Essential Medicines List Committee to enable its rollout.

Gilead has secured a deal with the Global Fund for HIV, TB and Malaria, as well as private donors, that will allow lenacapavir to be rolled out in eight African countries, including in South Africa at a cost to country of R1,080 ($60) per person per year.

Under this deal, private donations from the Children’s Investment Fund Foundation (CIFF) will also contribute toward procurement of lenacapavir. The foundation’s contributions will be above and beyond the $60 contributed by countries per person per year.

While the amount that Gilead will recoup for a year’s supply of lenacapavir under the deal has not been disclosed, it is speculated to be between R1,800 ($100) and R2,160 ($120), according to Warren.

He added that Gilead’s deal with the Global Fund would allow countries to begin budgeting and planning for lenacapavir’s rollout using Gilead’s product while they await the availability of more affordable generic products in a few years time.

The lack of transparency around Gilead’s pricing is uncommon in South Africa, which has strong legal requirements for medicine price transparency. Despite transparency concerns, the national Department of Health has indicated that it will participate in Gilead’s Global Fund arrangement.

By keeping the price secret, two advocacy groups, the Health Justice Initiative and Health Gap, have argued that the deal will undermine efforts in countries not included in the arrangement to negotiate and secure affordable pricing of lenacapavir.

Are HIV prevention injections cost effective for South Africa?

Local researchers have crunched the numbers to establish whether CAB-LA and lenacapavir offer good value for money.

These analyses compared the cost-effectiveness of HIV injections to the widely available prevention pills in public clinics, Lise Jamieson, a senior researcher at Wits HE2RO, told Spotlight.

The prevention pills provided by the Department of Health were purchased for R1,000 per person per year, said Jamaloodien.

Jamieson said that, according to modelling, prevention injections would avert more HIV infections than prevention pills. Generally speaking, products that provide protection for longer periods were more effective since their efficacy was less dependent on people regularly taking pills or going to the clinic to get an injection. We could thus accept a higher price for lenacapavir (providing six months of protection) than for CAB-LA (only two months of protection) because modelling indicated that this product would avert more HIV infections and delivered more treatment cost savings over time.

Jamieson said that according to the latest iteration of their cost-effectiveness modelling, which had not yet been published, CAB-LA needed to be capped about R1,800 ($100) per person per year to be cost effective, while lenacapavir needed to be capped at about R3,600 ($170) per person per year.

Based on this analysis, for South Africa to roll out lenacapavir at $60 per person per year is highly cost effective, while buying CAB-LA at $160 per person per year is not cost effective.

Lenacapavir use also requires fewer clinic visits per year than CAB-LA (two versus six) which places less of a strain on health facilities and providers.

Cheaper generic versions of lenacapavir and CAB-LA are expected to become available in 2027.

Lenacapavir generics, Warren said, were expected to enter the market around the same time as generic CAB-LA despite CAB-LA’s initial head start. This is because Gilead was quicker to license generic manufacturers and used a faster licensing approach than ViiV, he added.

Compared to CAB-LA, Warren said it would be faster to show that the generic version of lenacapavir worked the same as the original — a necessary step before generic products could be approved. Added to this, he noted that generic companies would probably move faster to bring lenacapavir to market because buyers showed more interest in it.

How will procurement of lenacapavir be funded?

While lenacapavir is cost effective for South Africa at $60 per person per year, purchasing it may nevertheless be challenging given the country’s tight healthcare budget.

HIV prevention pills are procured domestically in South Africa, but Jamieson said the country would need additional funds or donor support to roll out lenacapavir.

The national Department of Health and the Global Fund agreed to allocate R520-million of the country’s Global Fund grant towards buying lenacapavir, Bhekisisa reported in July. This allocation will allow more than 450,000 people in the country to access lenacapavir over the next three years.

Can lenacapavir turn the tide on the epidemic?

In addition to looking at the cost-effectiveness of long-acting injectables, Jamieson and her colleagues have modelled how the rollout of injectable HIV prevention options will affect new HIV infections in the country.

Jamieson said if South Africa initiated roughly a million people on lenacapavir over the next year and then increased access to reach 4 million people in the next 20 years, HIV incidence could fall below 0.1% by 2038 — with a projected 3.5 million people on lenacapavir by then. At this level, the country would effectively end the HIV epidemic.

Scaling up lenacapavir to this level will require significant political will and additional investment above and beyond what has already been committed by the Global Fund.

Meanwhile, researchers are working on new versions of lenacapavir and CAB-LA that could double the length of protection offered by each.

As Spotlight previously reported, there are promising signs for a lenacapavir formulation that could provide 12 months of protection as opposed to the current six, and a CAB-LA formulation that could provide four months of protection rather than two. 

HIV prevention tablets that provide a month of protection at a time are also under development. However, it remains to be seen whether these new formulations will succeed in the pivotal clinical trials testing their safety and effectiveness. DM 

 This article was first published by Spotlight — health journalism in the public interest. Sign up to the Spotlight newsletter.