Although HIV infections in South Africa have plummeted in 20 years, from highs of more than 500 00 to around 149 000 in 2023, new infections remain stubbornly above the levels required to end the HIV epidemic in the next decade.
Additionally, writes Catherine Tomlinson in Spotlight, local rollout of the latest technology in the arsenal to prevent HIV (the long-acting cabotegravir or CAB-LA injection, administered every two months) has been stalled because of high costs and limited global supply.
CAB-LA has been acknowledged as a potential game changer, but delays mean supply will probably need to be rationed for at least the next few years.
New HIV infections in 2023 were three times higher than HIV-related deaths – 149 000 versus 50 000 (roughly another 50 000 HIV+ people died of non-HIV-related causes in 2023), and the fact that the number of people becoming infected is higher than those with HIV who are dying means the absolute number of people with the virus is increasing.
In 2023, 7.8m South Africans had HIV. By 2026, this is projected to exceed 8m, meaning the country appears unlikely to meet the UN’s Sustainable Development Goal target to cut infections by 90% by 2030 (compared with 2010). To reach this target, new HIV infections must drop to around 40 000 per year.
“The consequences of the CAL-LA rationing will be more infections,” Doctors Without Borders’ Helen Bygrave told Spotlight.
CAB-LA, registered by the South African Health Products Regulatory Authority in late 2022, was shown to be highly effective at preventing HIV infection in two large trials partially conducted in South Africa. Both trials, conducted in women, men who have sex with men and trans women, were stopped early after CAB-LA’s effectiveness in preventing HIV was so apparent.
CAB-LA is even more effective than currently available oral PrEP – an already highly effective HIV prevention tool – because the injection, unlike oral PrEP, does not require users to remember or be able to take a daily pill.
In fact, the trials showed that CAB-LA virtually eliminates the risk of contracting HIV for the two months per shot. Research on jabs that provide four and six months of protection is under way.
Modelling work to assess the impact of introducing CAB-LA in South Africa suggests it has the potential to significantly reduce new infections, and with broad rollout, could prevent up to 52 000 HIV infections annually, compared with up to 16 300 when only using oral PrEP.
Dickering over price tags
One snag has been uncertainty over CAL-LA’s price. After years of advocacy by medicine access advocates for an affordable and transparent price, late last year ViiV, which makes CAB-LA, finally settled on a cost of about $30 per injection.
However, although ViiV said this is a non-profit price, the lack of public information about the company’s production costs makes it impossible to judge whether this is actually its at-cost price.
And the bad news is that the price quoted is more than what the country says it can pay.
The National Essential Medicines List Committee published a budget impact analysis in February 2023 stating that the cost of CAB-LA could not exceed more than twice the cost of two months of oral PrEP for it to be cost effective and procured by government (about R130).
Apart from exceeding the threshold price, the cost of making CAB-LA broadly available in the public sector may simply be unaffordable, given the country's already strained health budget.
Assessing potential cost is particularly tricky for preventative medicines where uptake is unpredictable. When assessing the budget required to procure a therapeutic medicine, buyers like South Africa consider how many people have a condition requiring the medicine. But for a preventative product – targeting the general population – it is impossible to know how many people will actually use the product.
Researchers at the University of the Witwatersrand’s Health Economics and Epidemiology Research Office have been grappling with the issue. Depending on how many people start CAB-LA and how long they stay on it, the researchers estimate it will cost the government between R3.9bn and R11.4bn per year.
Prices are anticipated to drop substantially when generics enter the market in three or four years’ time, so some argue that the high price might be worth paying, given that it would only be for a few years.
Yet for an overstretched health budget that is probably facing even more cuts, it is hard to envision where the money would come from.
The hope is that, at least for the next few years until cheaper generic CAB-LA is produced, global donors will help the government cover the costs of providing CAB-LA.
“Short-term affordability is difficult,” said Professor Linda-Gail Bekker, CEO of the Desmond Tutu HIV Foundation. “I think we’re going to need help and that’s where Pepfar [the US President’s Emergency Plan for Aids Relief] and other agencies come into the mix.”
Spotlight understands the government is in communication with Pepfar regarding potentially receiving donations of CAB-LA.
Pepfar has procured around 300 000 vials of CAB-LA from ViiV for use in select low- and middle-income countries until 2025, said Mitchell Warren, CEO of New York-based NGO AVAC, and will focus its rollout in select African countries, which may include South Africa.
ViiV says around 1.2m doses of CAB-LA will be available for low- and middle-income countries until 2025, which includes the 300 000 doses procured by Pepfar.
The 1.2m doses would allow 200 000 people to take CAB-LA for one year (one person would require six doses for a year’s worth of protection).
Will prices drop?
A challenge for CAB-LA’s market viability is that its cost-effectiveness is judged against the cost of oral PrEP. The medicines used for oral PrEP are also used for HIV treatment and, with enormous manufacturing scale and broad generic competition, extremely cheap.
While ViiV currently maintains a market monopoly on CAB-LA and can unilaterally set its price, it yielded to advocacy pressure and licensed three generic companies to manufacturer CAB-LA in March 2023.
This is expected to cut costs, but generic availability is still several years away as the licensed generic companies must still establish manufacturing capacity and gain regulatory approval for their products.
When generic versions enter the market, CAB-LA’s price may fall significantly, and it could be sold at prices similar to those for oral PrEP.
Doctors Without Borders’ Access Campaign pharmacist Jess Burry said that to achieve these lower prices, however, more generic manufacturers should be licensed to bolster competition.
If this had been done sooner, in earlier stages of drug development, generic products would be available earlier than the current expectation of 2027.
If South Africa does not procure CAB-LA, says Warren, it may have a dampening effect on the global market for the product, which may in turn discourage or delay generic companies from investing in establishing and building up manufacturing capacity.
That’s because in the HIV market, South Africa is an influential buyer. Pepfar, the Global Fund and the SA government are the three largest buyers of HIV treatment globally.
And despite the relatively low levels of oral PrEP uptake and coverage in South Africa, the country has still put more people on oral PrEP than any other country.
Of the estimated 6.2m people who have ever been started on oral PrEP globally, 1.3m are in South Africa, compared with only 441 000 people in the US.
Warren said it was imperative to build a South African market for CAB-LA.
“If we don’t demonstrate demand, generic producers will ask why they should spend money building [manufacturing] capacity if no one is buying the product.”
Seen in this light, the case for paying R570 per injection for three or so years starts to look more reasonable, especially if donors like Pepfar can help pick up the tab.
Decision-makers might still baulk at the price tag, but they should at least consider the potential opportunity cost of not buying CAB-LA.
The jab is currently only available here through implementation studies (with doses donated by ViiV), and which are reaching only a minuscule fraction of those who could benefit from CAB-LA.
As with oral PrEP and Covid-19 vaccines, the eventual level of uptake will in part depend on how easy the jabs are to get and how they are promoted. But exactly when CAB-LA will be dispensed more broadly remains a big unanswered question.
What is clear is that over the next few years until more supply is available at more affordable prices, South Africa will need to ration its rollout of CAB-LA.
Rationing also raises difficult questions of who the recipients of the limited supply should be.
While limiting eligibility can ensure the product gets to the most high-risk groups, it has the drawback of potentially stigmatising use of the product.
The oral PrEP rollout in South Africa initially was restricted to sex workers and men who have sex with men, creating the idea in some quarters that oral PrEP was meant only for these.
If South Africa does not receive donated CAB-LA or declines to buy it at ViiV’s price, then it will probably remain unavailable here for the next few years, and many avoidable new HIV infections will occur.
See more from MedicalBrief archives:
Health Department slams cost of anti-HIV CAB-LA shot
HIV-prevention jab rolled out in pilot project
Why SA pilots of HIV prevention shots and vaginal rings have been delayed