South Africa is expected to begin piloting injectable pre-exposure prophylaxis (PrEP) in 2023, health financing mechanism Unitaid tells aidsmap. The demonstration study will be the first of many hoping to answer the single biggest challenge for a rollout there and beyond: How to take a surprisingly complicated injection out of clinics and hospitals and into communities.
Adolescent girls and young women in South Africa will be the first to access injectable PrEP using the antiretroviral drug cabotegravir every other month as part of the Unitaid-supported demonstration project. The pilot will follow regulatory approval for the drug, which Unitaid expects in early 2023.
Zimbabwe recently became the first African country to approve long-acting cabotegravir as PrEP. Only two other countries – the United States and Australia – have approved it, but just days ago, the European Medicines Agency confirmed it had formally accepted drugmaker ViiV Healthcare’s application for eventual approval in the European Union.
A similar demonstration project for the dapivirine vaginal ring — also a form of PrEP — is expected to begin this month, Unitaid confirmed. Both pilots will be run by the Wits Reproductive Health and HIV Institute (Wits RHI).
Wits RHI’s pilot of the HIV prevention injection will be the first of several implementation studies envisioned by the South African National Health Department that will inform a national rollout, the department’s Hasina Subedar said at the 24th International AIDS Conference in July.
“What we learned from oral PrEP is that… [studies] learn in a very controlled environment and it doesn’t necessarily reflect the real-world situation in our public health facilities,” she said. “There needs to be central coordination of all these projects so that they answer the questions that will assist us in making a decision about scale-up of the product.”
The vast majority of the country’s 5.5 million people on HIV treatment receive their antiretrovirals through the public sector. PrEP provision remains similarly concentrated.
Nurses already trained to provide treatment likely to provide injectable PrEP
South Africa accounted for about one in 10 people on oral PrEP globally in 2020, data collated by the HIV prevention advocacy organisation AVAC shows. The country — together with Kenya and the United States — made up about 40% of people on oral PrEP globally.
Many of the details of a national rollout will be in part decided by how the national regulator, the South African Health Products Regulatory Authority (SAHPRA), classifies the HIV prevention injection, Subedar explained. Restrictions imposed by the regulator (known as schedules) will determine who can administer it, for example. SAHPRA could also choose to limit the injection for certain groups, depending on available data.
Experts in the country are already thinking about the who, where and how of the rollout — provided the every-other month injection becomes affordable. Specially trained nurses will need to provide the injection, most experts agree. Just how injectable cabotegravir, which is difficult to administer, will be taken into communities and closer to patients is less clear. Mobile health services and even new, community ‘shot clinics’ may all be part of decentralised models that will provide the injection alongside other sexual and reproductive health services. Finally, healthcare workers will have to figure out how to counsel people on something almost completely novel: Real choice in HIV prevention.
“Activists want us handing stuff out on street corners yesterday — that certainly was the feeling at the International AIDS Conference in Montreal,” Dr Francois Venter, divisional director of the research institute Ezintsha, said at a recent meeting of the Southern African HIV Clinicians Society in Johannesburg. “There needs to be a bit of a stock taking before we do that.”
“But our patients are going to be pushing us to go very fast,“ he continued. “We've got some time to figure [injectable PrEP] out but we can’t sit on our hands wondering about it for years."
The big question: Where to provide the injections
Dr Saiqa Mullick is director of implementation science at Wits RHI, which was one of the first organisations in South Africa to partner with the national health department to provide oral PrEP. The rollout began initially with sex workers and then later to young women and, eventually, their partners.
“One lesson that we have learnt was that even though we focused very much on PrEP for adolescent girls and young women, we started seeing men coming in for prevention services,” she said.
Mullick believes that, at least initially, providing injectable PrEP will fall to a relatively small cadre of nurses already trained to provide HIV treatment and oral PrEP in South Africa. Even these nurses however will need additional training.
But working out locations in communities from which to provide the HIV prevention injection will be more tricky.
“That is one of the biggest implementation science questions that we need to answer quickly,” said Professor Linda-Gail Bekker. Bekker is the chief operating officer of the Desmond Tutu Health Foundation and a past president of the International AIDS Society. “Pills made differentiated service delivery so incredibly easy: You can send pills by courier…give people multi-month dispensing…I can’t do that with long-acting cabotegravir.”
Differentiated service delivery models typically include moving services out of facilities, reducing clinic visits or task-shifting services to make care easier and better for patients.
Bekker believes that community ‘shot clinics’ might be part of how injectable PrEP services look in the future — alongside traditional hospitals, clinics and mobile outreach services.
"Just how injectable cabotegravir, which is difficult to administer, will be taken into communities is unclear."
“You need a nurse who is specially trained to give an injection, which needs privacy — be it only every two months. Still, for that, you need infrastructure,” she says. “We are going to look and see if we can do a shot clinic: A trailer with the nurse and the counsellor, so if I'm just needing my maintenance shot, I literally go and get my shot and leave.”
Both the Desmond Tutu Health Foundation and Wits RHI have also invested heavily in offering oral PrEP via specially-created youth-friendly spaces, including at public clinics.
These options allow young people to skip the usual clinic queue, explains Wits RHI linkage to care officer Khanyi Kwatsha — and the prying eyes of older community members who often judge young people for seeking out sexual and reproductive health services.
“You will find that we initiate a young girl on PrEP and then the girl will come back to say that her parents threw away the PrEP because they thought… she was too young to have sex,” Kwatsha explained. Wits RHI now holds regular community events, including at churches, aimed not just at young women and other key populations, but also at their friends and family. “By involving their parents, we are making sure we sensitise the whole community on how youth can have safe sex in a way whereby they don’t jeopardise their future.”
Several services have also taken oral PrEP on the road, offering it via mobile clinics that Mullick said she believes could be an option for injectable PrEP delivery.
Still, coordinating mobile PrEP clinics can be challenging, and requires a complicated tracking system to ensure that mobile clinic visits align with patients’ medication schedules, Mullick says.
Paul Botha is a site coordinator for Engage Men, which offers PrEP to gay, bisexual and other men who have sex with men in Johannesburg. Engage Men does this in part by recruiting community ambassadors who hold information sessions for the gbMSM community at homes or bars. Botha admitted that Engage Men’s mobile clinics have struggled to keep pace with rising demand and to deal with no-shows.
“In terms of our messaging, we have to make sure that people know we're going to deliver to them once,” he said. “If they’re not there, they forfeit the [delivery] service.”
Why it might be time to change how the world measures PrEP use
Part of Kwatsha’s job at Wits RHI is to call patients who have missed appointments and for some, a ‘no-show’ is a sign that they no longer feel at risk of HIV. They may not be having sex, or had a change in relationship status. When their perception of risk changes, they may call her back again to restart PrEP.
Mullick says data on people who have cycled on and off oral PrEP has been difficult to track within the public health system but has been growing.
"You should be on PrEP when you're in a season of risk. It’s not HIV treatment — you don’t have to be on it for a lifetime,” she explains. “You can be off it when you're not at risk and come back to reinitiate.”
Mullick continued: “That message is definitely coming through… because restarts are going up.”
Until now, PrEP programmes — unable to track patients over time in many countries — have measured success by how many people had ever started taking the pill. Few are able to say definitively how many people are on PrEP at any given time.
Under the Unitaid grant, Wits RHI will be looking to better understand — and track — how people cycle on and off oral and injectable PrEP as well as the vaginal ring.
“The field is now thinking about how to measure PrEP use in a more meaningful way,” Mullick added.
Choice will be key to increasing uptake
Mullick, Bekker and Botha all agree however that regardless of how healthcare workers take the HIV prevention injection into communities, it will have to be provided at least alongside a wraparound package of sexual and reproductive health services.
Meanwhile, messages around the HIV prevention injection will have to hit the mark with communities.
Healthcare workers will have to figure out how to counsel people on something novel: Real choice in HIV prevention."
“The field has learned a lot more about how to message PrEP and positioning it as a wellness product with empowering messaging,” Mullick explains. “We have put forward that you have the power to take into your hands your health and wellbeing — that’s the big thing we learned.”
For almost four decades, a person’s HIV prevention options were largely confined to the condom. Now, with injectable PrEP and the dapivirine ring in the pipeline, healthcare workers will have to change the way they think — and talk about prevention choice to patients and communities.
“Our providers have never had to counsel around the choice of biomedical options,” she added. “The choice aspect is really important because what we've learned from family planning programmes is that the more choices you have, the more coverage and impact you're going to get.”
Correction: This article was amended on 7 November 2022. The previous version stated that cabotegravir requires refrigeration.