The new HIV-prevention injection is now available to a select number of people in South Africa, with the fact that a single shot provides two months of protection being one of the jab’s major selling points, writes Elri Voigt for Spotlight.
Earlier this month, a young Capetonian became one of the first people in the country to have the injection – containing a long-acting formulation of the antiretroviral drug cabotegravir (CAB-LA) – outside a clinical trial.
The recipient had responded well and said the injection was less painful than a sexually transmitted infection (STI) injection they had received in the past.
While it is not readily available for most people just yet, a select number of South Africans will be able to access it via several implementation studies. One of these pilot projects is called FAST PrEP, conducted by the Desmond Tutu Health Foundation (DTHF) in Cape Town.
Technically, access to the injection is limited to a FAST PrEP sub study called Prepare to Choose.
Other forms of pre-exposure prophylaxis (PrEP) are vaginal rings and injections.
Elzette Rousseau, a social behavioural scientist and lead co-investigator in the implementation team for FAST PrEP, said that on the first day it was offered, five people opted for the CAB-LA shot.
By 21 February, 19 injections in total had been administered.
‘Real-world experience’
Professor Linda-Gail Bekker, CEO of the DTHF and principal investigator of the study, said after CAB-LA had demonstrated efficacy in phase three clinical trials, it was decided to first do some implementation science studies in SA, alongside the other new PrEP option – the dapivirine vaginal ring (DPV-VR) – before rolling it out in the public sector.
Both the CAB-LA injection and the dapivirine ring have been approved by the South African Health Products Regulatory Authority (SAHPRA).
The implementation studies can help transition the product from the clinical trial setting to a real-world roll-out in the public sector, she added, and detect any potential issues or safety concerns possibly not spotted in the clinical trials.
Pilot projects also help gauge the demand for products like CAB-LA and the DPV-VR, which can help with advocacy efforts and give the manufacturers and companies who create generic products an idea of whether they are worth investment.
“There really are limited pilots in the country so far,” she said. The pilots offering CAB-LA in addition to the DTHF are being conducted by Ezintsha and Africa Health Research Institute (AHRI), as well as the Wits Reproductive Health and HIV Institute (Wits RHI).
CAB-LA delays
Bekker told Spotlight the volumes of CAB-LA available in SA remain constrained for now.
While SAHPRA approved the injection in late 2022, limited supply and the product’s high price resulted in limited global uptake. A recent HIV investment case for South Africa found the injection not to be cost-effective at its current price, compared with PrEP pills.
For now, the only supplier of CAB-LA is ViiV Healthcare. Generic products are anticipated to enter the market in three to four years.
Despite SAHPRA approval for the product, the pilot projects have experienced delays in getting CAB-LA to their participants including that packaging did not meet South African regulatory requirements.
Bekker said that an alternative is to import CAB-LA through a phase 3b study (in this case, the Prepare to Choose study), approved by SAHPRA’s Clinical Trial committee.
Writing up protocols and having the study approved by an ethics committee and SAHPRA took some time, and once approved, CAB-LA still needed to be imported and ViiV Healthcare had to ramp up manufacturing to meet demand.
Thus far, CAB-LA has not yet been bought by the National Department of Health for public distribution, and the only other way to get the drug into the country will be through a donation by the US President’s Emergency Plan for Aids Relief (PEPFAR).
“PEPFAR has been able to import the product into Zambia and Malawi…as the first two PEPFAR countries to get it in a donated public roll-out, and we hope South Africa is in that queue,” she said.
Prepare to Choose study
At the moment, Prepare to Choose can only offer CAB-LA to a few hundred people. Bekker said ideally, they would have wanted to offer all of their FAST PrEP clients a three-way choice of either the vaginal ring, oral PrEP pills or CAB-LA. But for now, CAB-LA is only being offered within Prepare to Choose – a single-nested sub-study within FAST PrEP.
Mapukata, who was present during the first CAB-LA injection in the implementation study, said it would be interesting to see what participants choose now that that they have an additional PrEP option.
“People have been waiting for an injection for the longest time, so we are seeing lots of excitement,” she said.
Prepare to Choose currently has enough CAB-LA doses for 900 participants over an 18-month period.
So far those who have chosen CAB-LA are primarily adolescent girls and young women – average age 22. Some have been on PrEP before, others are starting PrEP for the first time.
Trends in FAST PrEP
FAST PrEP is being implemented at 12 public sector health facilities in the Klipfontein and Mitchells Plain Health Sub-Districts in the Western Cape, and in four mobile clinics.
Nearly 11 000 participants have enrolled, Rousseau said, meaning 11 000 people have accessed either prevention pills or the DPV-VR through the study.
When FAST PrEP started, the assumption was that the study would enrol between 20 000 and 23 000 participants, but it is not necessarily targeting to enrol that exact number. The study currently has funding to continue offering PrEP until late next year but access to these options might continue beyond that.
The study reaches participants in public sector healthcare facilities by having two peer navigators in each facility – young people trained and employed by the study co-ordinators, who can educate and counsel young people about FAST PrEP.
The study co-ordinators also offer training, particularly sensitisation training, to nurses and other staff.
The four mobile clinics travel around the Klipfontein and Mitchells Plain Health Sub-Districts, including 16 secondary schools, where they have permission to enter the school grounds.
Demand for the DPV-VR
So far, just under 200 women in the study have chosen to use the DPV-VR. (Not everyone is eligible to use the ring: it is offered to women over 18, who are not pregnant and not breastfeeding).
For participants eligible for both the ring and oral PrEP, the pill is still more popular – with a rough estimate of around 15% of eligible participants choosing the ring.
Most participants, at this stage, who choose the ring, have either tried oral PrEP first and struggle to take pills daily or found it doesn’t suit their lifestyle. Very few have started on the ring and then switched to the daily pill.
Counselling for Choice
While the ring was found to be effective in two phase 3 trials, its efficacy in those trials was far from 100%, and evidence for its efficacy is generally less impressive than for the pills and the injection. Interpreting findings from PrEP trials is also somewhat muddied by whether or not pills are taken as prescribed, and the ring is used and replaced as prescribed.
Compared to placebo, there was a 30% reduction in HIV infection for ring users in phase three trials, and a 50% to 60% reduction in infection when the ring went to open-label, Bekker noted.
She said clinical trial efficacy results can differ from real-world results, particularly regarding HIV prevention. For instance, oral PrEP in clinical trials initially showed no evidence of efficacy in the prevention of HIV in women. Yet, real-world evidence showed it works in all populations if taken as prescribed.
What both these cases have shown, she added, was that it’s not necessarily that the product isn’t working, it’s that the product isn’t always being used as intended.
Regarding the ring, the drug within the ring is efficacious and will kill the virus, but the ring must be present when the individual is exposed to HIV. “Once you take the ring out, the (prevention) effect is lost,” she said.
See more from MedicalBrief archives:
Health Department slams cost of anti-HIV CAB-LA shot
HIV prevention pill uptake in SA climbs to 1m users
Zimbabwe the first to green-light injectable HIV prevention drug
Cost and uncertainty over uptake bedevil Africa’s uptake of injectable PrEp
SA firm to produce contraceptive anti-HIV vaginal rings