Last year it was reported that pilot projects testing out a new HIV prevention injection and a vaginal ring in South Africa would start early in 2023. Yet, as delegates gathered for the 11th SA Aids Conference in Durban recently, those pilots hadn't even begun, write Alicestine October and Elri Voigt for Spotlight.
The latest estimates from Thembisa, the leading mathematical model of HIV in South Africa, show new HIV infections are declining, but at 164 000 in 2022, are still high.
At the conference, several delegates called for a basket of prevention options suited to people’s (especially young women’s) needs.
The most recent alternative is pre-exposure prophylaxis (PrEP), which can be via a daily pill, a monthly vaginal ring, or an injection every two months.
Where we are with PrEP
Thus far, oral PrEP, approved by the South African Health Products Regulatory Authority (Sahpra) in 2015, has been rolled out in more than 2 000 public healthcare sites countrywide at last count in November 2022. But uptake has been slow.
Thembisa reports that only 0.8% of sexually active people were taking oral PrEP in 2022 – up from 0.1% in 2018.
Sahpra approved the dapivirine vaginal ring in March 2022, and implementation studies are planned to determine its feasibility here.
Nicolette Naidoo, technical head of research for implementation science at the Wits Reproductive Health and HIV Institute (Wits RHI), told Spotlight the studies are only expected to start on 1 July this year.
In December 2022, Sahpra authorised the use of the long-acting HIV prevention injection containing the antiretroviral medication cabotegravir (CAB-LA). The shot is administered every two months and has been extremely effective in two large trials.
The high efficacy of the injection compared with pills or the ring is thought to be largely driven by the higher levels of treatment adherence associated with the jab. But how good adherence will be outside a study context is not known.
To roll out the injection, as with the vaginal ring, implementation studies or pilot projects are needed to assess how they will perform in South Africa.
Spotlight previously reported that CAB LA pilots were expected to start early in 2023.
However, Dr Sandile Buthulezi, director-general in the National Department of Health, said there had been delays and that a technical working group was still finalising protocols.
Importance of pilots
“A number of PrEP introduction studies have been planned this year to introduce cabotegravir and the dapivirine ring in SA,” Professor Sinead Delany-Moretlwe, director of Research at Wits RHI, told delegates at the SA Aids conference.
These will show how to deliver CAB-LA and the ring in the local health system, how to deliver differentiated and simplified services for various populations, how to deliver HIV testing as well as reveal more information on the cost and benefits for HIV infections averted, and what the demand for the products will be.
There are still some key questions around CAB-LA that need to be answered in a study setting, Naidoo said, like the potential for HIV drug resistance and what the most sensitive testing algorithms would be for detecting infection.
“But also, it is an intramuscular injection, so the questions around feasibility are also important. Does it (the injection) need to only be done in a facility? Can it be done in a community?”
CAB-LA delays
National health spokesperson Foster Mohale said the CAB-LA pilot studies are awaiting donations from manufacturer ViiV.
“There have been challenges with the packaging of the donated product not meeting South African regulatory requirements,” he said.
When Sahpra approves a product, certain specifications are required for packaging.
Since the donated product does not meet these specs, the originally intended pilots as implementation science studies, which are real-life study environments, may have to be changed to 3B studies –more like a clinical trial and different from what was initially envisaged.
He said ideally, the department prefers a study, which is closest to real life and where it can actually offer oral PrEP, with the dapivirine ring, and CAB-LA together, so people have a choice.
Mohale said the delay is not caused by the development of the protocols and training materials. “These are already in draft form and being reviewed.”
Professor Linda-Gail Bekker, Desmond Tutu Health Foundation CEO and director of the Desmond Tutu HIV Centre at the University of Cape Town, conceded the South African pilots that will use CAB-LA “hit a bit of a roadblock on getting the product here because we still need to get it labelled for SA”.
“ViiV is making available enough CAB-LA for the pilots so each of us (research organisations involved in the pilots) have had to say how much we need … that’s all gone through,” she said.
The Foundation and Wits RHI are among the entities involved in the pilots, which were expected to start around July this year. “But it’s more like September now.”
Cost concerns
The other issue is the price of both CAB-LA and the ring.
Mohale said the national essential medicines list committee considered both the dapivirine ring and CAB-LA as pre-exposure prophylaxis interventions.
When this committee considers whether something needs to be included on the national essential medicines list, it looks at various things, including cost.
“Because of the costs of the dapivirine ring – quite astronomical – they weighed it against oral PrEP, which costs R52 for a month’s supply whereas the dapivirine ring costs more than R300.”
So, for the dapivirine ring, the committee did not recommend inclusion on the list, but they will reconsider this once the price is comparable to oral PrEP.
With CAB-LA, however, the department still does not have an absolute price at which we would get CAB-LA, he said.
“Right now we’re still talking about the donated product, but the actual price at which we’re going to get it …we don’t know.”
Another factor is the limited global supply of CAB-LA, with only one company making it: ViiV.
“The Medicines Patent Pool got involved now so there will be an opportunity for generic companies to at least fill and finish or even start manufacturing, but there’s going to be a lead time to that,” Bekker said. “But hopefully, the pilots will start soon … It is worth knowing the treatment injectables are already being used in a number of implementation science projects and at least we are learning valuable information there.”
A representative from the Medicines Patent Pool last year told Spotlight that it is expected to take three to five years before generic versions of CAB-LA will become available.
ViiV responds
A ViiV spokesperson told Spotlight this week that the company had committed to offer a not-for-profit price for public programmes in low-income, least developed, and all sub-Saharan African countries until a generic is available, including South Africa.
“We are also working with major global partners with a shared ambition to enable access to cabotegravir LA for PrEP. Additionally, we recently announced progress on our new voluntary licence with Medicines Patent Pool to help enable access as MPP signed sub-licenses with Aurobindo, Cipla, and Viatris to produce generic versions of CAB- LA for PrEP. ViiV and MPP will be working with these partners to enable generic product development, manufacturing, and supply of cabotegravir LA for PrEP as quickly as possible.”
Ring projects ready
Meanwhile, said Mohale, the dapivirine ring pilots were due to start in June but there was a delay for the post-importation testing.
“But we should start in July. We have trained all the people who will be implementing this and right now, the rings that were donated are being distributed to the study sites.”
The department has already received 38 400 dapivirine vaginal rings from USAID for implementation science pilot projects that have approved ethical and IRB approval.
The department has identified 10 such projects – in nine provinces – that meet the requirements to utilise these.
Naidoo said at the study sites the ring will be offered alongside oral PrEP. People must enrol in one of the studies, which will provide useful data like what the preference is for the ring and whether participants will switch between the ring and oral PrEP.
“They are implementation science studies, so they will be happening in local clinics and real-world settings in communities and will answer the key questions regarding acceptability, feasibility and so on.”
See more from MedicalBrief archives:
SAHPRA approves ‘game-changer’ vaginal ring but DoH still undecided
Cipla to produce anti-HIV injection in Benoni, Durban
Cost and uncertainty over uptake bedevil Africa’s uptake of injectable PrEp