Unpacking the HIV jab that could dramatically reduce new infections

We’ve come a long way from the worst days of South Africa’s HIV epidemic, but the virus still claims more than 50,000 lives per year and, even in 2026, annual new infections remain stubbornly high at more than 140,000.

Reducing the rate of new infections is not an easy task. The most effective measure is to make as many as possible of the roughly eight million people who are living with the disease non-infectious. The good news is that most people with HIV become non-infectious once they are stable on antiretroviral treatment. The bad news is that the growth of South Africa’s HIV treatment programme has slowed. The pool of infectious people thus seems set to remain relatively large.

For people who are not living with HIV, the most effective form of protection over the years has been the correct use of condoms. Another benefit of condoms is that they protect against other sexually transmitted infections.

But condoms aren’t the only game in town. Voluntary medical male circumcision substantially decreases men’s risk of contracting HIV, and also provides indirect protection for women.

And then there are antiretrovirals (ARVs) to prevent HIV infection. Landmark studies published in the 2010s showed that taking a tablet that contains the antiretroviral medicines tenofovir and emtricitabine could reduce someone’s risk of contracting HIV to near zero. Such tablets are commonly referred to as oral pre-exposure prophylaxis, or oral PrEP. For several years now, these HIV prevention tablets have been widely available in South Africa’s public healthcare system, although uptake has been somewhat muted. Modelling work from Thembisa, the country’s leading mathematical model on HIV and TB, suggests that only a few hundred thousand people are taking the tablets.

The long-acting revolution

One challenge with HIV prevention pills is that not everyone can, or wants to, take them every day. For some, taking ARVs, or being seen to take ARVs, still comes with a dose of stigma. For others, remembering to take a pill every day can be tricky. Ultimately, the incentives for healthy people without HIV to take prevention medicines simply aren’t as compelling and immediate as they are for people who already have the virus in their bodies.

As in some other areas of medicine, one solution to this treatment adherence challenge is simply to make it more convenient to take. Many women, for example, prefer three-monthly contraceptive injections or three-yearly implants to a regular pill. There is some evidence that similar preferences apply to HIV prevention medicines.

So-called long-acting therapies do what the name suggests – act over longer-than-standard periods. They could take many forms, from slow-release tablets to injections that leave a depot under the skin that slowly releases drugs into the bloodstream, to small implantable devices that are typically left in the arm for several years.

The first long-acting HIV prevention option to take the world by storm was an injection. It made headlines in 2020 when a pivotal study found it to be more effective than the daily prevention pills – the difference being largely due to better adherence, rather than differences in the ARVs used. This jab, containing the antiretroviral drug cabotegravir, provides two months of protection against HIV infection at a time.

Two years later, the World Health Organization recommended the jab, called CAB-LA, for HIV prevention, and it was registered for use in South Africa. Roll-out beyond an implementation science setting stalled however when the prices the drug’s manufacturer ViiV Healthcare was willing to sell it for were deemed unaffordable by the South African government.

Fortunately, a new prevention jab that provides protection for three times as long as CAB-LA was on the way. In 2024, two large studies, found an injection of the antiretroviral drug lenacapavir given every six months was almost 100% effective in preventing HIV infection. These findings would later be hailed as the journal Science’s 2024 scientific breakthrough of the year. It is this “breakthrough” that is being rolled out in South Africa from June 2026.

Two often-neglected groups in HIV research – adolescents (aged 16 and 17), and women who become pregnant while in a study – were included in clinical trials of lenacapavir. The jab was found to be safe in both populations, which means it can now be offered to adolescents and pregnant women in the South African roll-out.

Lenacapavir is injected just under the skin, typically in the stomach area, where it forms a small depot that very slowly releases the drug over time. These depots can form small lumps under the skin. Though harmless and usually not visible, it will be important that people getting the jab know to expect these “subcutaneous nodules”. The other most common side-effects seen in the two pivotal studies were pain at the injection site and a skin rash. These reactions and the size of the nodules appear to decrease with subsequent injections.

Before their first injection people will have to have an HIV test to ensure they aren’t already living with HIV. This is important since treating someone with HIV with just lenacapavir could result in the development of drug resistance. Together with the injection, people starting lenacapavir will also have to take some lenacapavir tablets for two days. Since the depot releases the injected drug very slowly, these tablets are needed to get the drug levels in the body up more quickly so that it can provide full protection as soon as possible. The Department of Health has published a guideline document setting out how it should all work at the clinic.

In addition to the lenacapavir and CAB-LA jabs, there is also a long-acting vaginal ring that contains the ARV dapivirine. The ring provides one month of protection at a time, with a three-month version also under development. The available evidence however suggests that the dapivirine vaginal ring is not as effective at preventing HIV infection as oral PrEP or the two injectable options.

The long road to jabs at clinics

Having the scientific evidence that an injection works is, of course, only one step in that jab’s long journey to the point where people can get it at clinics. An essential next step was regulatory approval, which lenacapavir received from the South African Health Products Regulatory Authority in October 2025. After regulatory approval was secured, the next question became whether a sufficient supply of the product can be procured in South Africa on acceptable terms.

Lenacapavir is currently only being produced and marketed by the pharmaceutical company Gilead Sciences, who holds the critical patents on the product. In the US, lenacapavir is sold for about $28,000 per person per year. The Global Fund (the world’s largest multilateral funder of health in low- and middle-income countries) and Pepfar (the US President’s Emergency Plan for Aids Relief) are however procuring limited stocks of lenacapavir at a lower price for use in some low- and middle-income countries. It is some of these Global Fund-procured jabs that will be used in the first phases of the lenacapavir roll-out in South Africa.

For now, largely due to the limited stocks, the local roll-out will target only about half a million people at 360 clinics in areas with high HIV rates, but the plan is to scale up considerably in the next few years.

The South African government is likely to start buying lenacapavir from generic manufacturers in 2027 or 2028. Gilead has so far issued licences that will allow six different companies to produce lenacapavir and to sell it in 120 different countries, including South Africa.

The Gates Foundation and a partnership including Unitaid, the Clinton Health Access Initiative and Wits RHI, have concluded separate deals with generic manufacturers that should see these generics sold for a price of no more than $40 (under R800) per person per year. This is lower than what the government currently pays for oral PrEP and modelling work suggests it would be affordable for the South African government. Barring any unforeseen hiccups, the pieces are thus in place to facilitate widespread access to lenacapavir in South Africa in the coming years.

For now, none of the generic versions of lenacapavir will be produced in South Africa. However, negotiations are under way that may eventually see a local company licensed to produce the jab. Such local production is seen as important for ensuring security of supply, although it is not clear that local companies will be able to compete with Indian generic drug-makers on price.

At the time of writing, neither the lenacapavir or CAB-LA injections can be bought at private sector pharmacies in South Africa. Oral PrEP can be bought for about R300 for a month’s supply. The monthly dapivirine vaginal ring should cost in the region of R500 per ring. (These prices are based on the 30 April 2026 Single Exit Price database published by the health department.)

How many people will want the jab?

One of the big unanswered questions about lenacapavir is how many people will come forward to get the jab. We are hopeful that the Department of Health will routinely provide detailed numbers on uptake in the coming months and years.

The initial roll-out is largely clinic-based, but researchers will also be assessing how well distribution works through mobile clinics. We need not stop there, of course. At the height of the Covid-19 pandemic public sector users could access SARS-CoV-2 vaccines from nurses at private sector pharmacies. With sufficient political will, the same could be done with lenacapavir. No doubt some young people would rather get their jab at the mall than at the clinic.

Those in control of the roll-out will have to think carefully about how they promote and provide the jab. At its core, it is an empowering tool that can help people stay HIV-free, but as often is the case with HIV-linked products, there is a risk of stigma. In addition, even though lenacapavir is not a vaccine, some vaccine scepticism might well transfer over to lenacapavir since it is administered as an injection. As with any large healthcare intervention, one will not have to look far to find lenacapavir-related misinformation on social media.

Either way, just having the jab at clinics and hoping people will come and get it might not be good enough if we’re hoping to see good uptake. Fortunately, we have several research groups and NGOs in South Africa who have world-class expertise in just this type of issue. Hopefully the government will draw on this unique reservoir as it adjusts and shapes the lenacapavir roll-out.

What’s next

The roll-out of the lenacapavir jab in South Africa will not be the end of our HIV prevention story. Two promising products in the pipeline are a new formulation of lenacapavir that looks like it could provide a full year of protection per shot, and a pill containing another antiretroviral that could provide a month of protection at a time. We are keeping a close eye on the ongoing development of these products. There are also still hopes that an effective HIV cure or vaccine might one day be developed, although this is a much longer shot than better long-acting antiretroviral formulations.

In the meantime, though, twice-yearly lenacapavir is rightly dominating the headlines.

Modelling suggests that over the next 20 years, an ambitious lenacapavir roll-out could reduce new HIV infections by about 20% to 30%. There can be little doubt that, like condoms and antiretroviral treatment for people living with HIV, providing lenacapavir at scale makes public health sense.

But thinking of lenacapavir mainly in terms of cost-effectiveness and public health benefits risks obscuring its more immediate and transformative human potential. For many people, especially young women, a discreet and convenient form of HIV prevention that they can control may well make the difference between contracting HIV or not.

As experts often point out, when it comes to products that can prevent HIV, choice – as in the world of contraception – is key. Some products will work for one person, but not for others. As circumstances change, a product that might have once worked may no longer be the best option. Having more than one product in the “toolkit of prevention” makes it easier to find what actually works in people’s lives.

For years, the HIV world has been flush with rhetoric about empowering young women – a group that is profoundly affected by HIV. An ambitious lenacapavir roll-out might be the most concrete realisation of those ideals yet. We simply have to get it right. DM

Disclosure: The Gates Foundation is mentioned in this article. Spotlight receives funding from the Gates Foundation, but is editorially independent – an independence that the editors guard jealously. Spotlight is a member of the South African Press Council.

This special briefing is part of a series by Spotlight – health journalism in the public interest. Sign up to the Spotlight newsletter.