Women in South Africa bear a disproportionate burden of the HIV pandemic. According to UNAids figures, of the more than 7.7 million adults living with HIV in South Africa, 62.7% are women and new HIV infections among young women aged 15-24 were more than double than those among young men. It’s for this reason that a group of Southern African young women were chosen for a study, known as the HPTN084 trial, headed by a research professor at the University of the Witwatersrand, Dr Sinead Delany-Moretlwe, to trial an injection called cabotegravir that is manufactured by Viiv Healthcare. The jab administered every eight weeks was found to be more effective than a daily pill to prevent HIV infection. Dr Delany-Moretlwe told BizNews that this breakthrough was a very important additional HIV-prevention option for women, and it could potentially cut the cost of the HIV burden for the country. According to UNAids data from 2019, South Africa is the largest consumer of generic anti-retroviral drugs in the world, and spends $1.54bn (R24bn) annually to run its HIV-programmes.- Linda van Tilburg
Well, we’re very excited about this result because I think it’s a really good news story for women. What we were able to show, is that an injection every eight weeks is nine times better than a daily oral pill in preventing HIV infection in women.We think the reason for this is that the injections have overcome a lot of the barriers that women experience taking a pill daily.
There’s the obvious habit issue, but in addition to that, I think women in particular, experience a lot of social pressure. There have been lots of reports of women experiencing stigma because they’re presumed to be HIV-positive and maybe because people make judgments about their sexual activity. I think they get pressure from partners who think they may be unfaithful. So, this is a discreet and convenient method that women can incorporate into their lives pretty much the way that many women use contraception. It’s a really important step forward for beginning to turn the tide on HIV infections in women on the continent.
This was a large trial and women from all over Southern Africa participated.
That’s right. You know, generally these large licensure trials are large. We evaluate new products in populations that would potentially use them, and by their nature, they are large. We enrolled over 3,200 women in 20 sites in seven countries – Botswana, eSwatini, Kenya, Malawi, Uganda, Zimbabwe and South Africa.
There are a couple of things. One, I think it’s represents a really fantastic Pan-African effort and reflects the good science that can come out of Africa. Two, I think it shows just how many women in sub-Saharan Africa recognise their HIV risk and want new prevention methods. We were able to keep the trial going during Covid-19 precisely because of the commitment of staff and participants.
What impact did the Covid-19 pandemic have on the trial?
We were really fortunate to be able to observe what was happening in the Northern Hemisphere and react early to put plans in place at site level to protect both staff and participants. Sites were very creative with how they ensured the safety of participants, to bring them to site, provide them with masks, provide them with a means for hand washing and hand sanitization. When lockdowns got very hard, they linked people to other agencies that were able to address things like food and security. So, there was a lot of attention paid to that.
The second concern was that we would potentially undermine the integrity of our data. But we had fantastic statisticians who worked with us to develop an approach on how we could manage the data. We monitored it and didn’t have to censor any of our data. We’re really pleased that despite the impact of the pandemic on the trial, there was relatively little impact and that’s why we’ve been able to generate the result that we have.
What is the current rate of HIV-infection in South Africa? What are you trying to prevent?
I think the statistics often quoted is that probably about 250,000 young women between the ages of 15 and 24 are infected with HIV annually. That translates to a rate of about 5,000 new infections in that age group a week. Earlier this year a vaccine trial reported results of an incidence of 4% of HIV infection. So, I think the reason that people are so excited about these results as well, is that in our trial, the overall incidence was 1%.
Obviously, the incidence was much lower in the cabotegravir group, but both Truvada and cabotegravir were effective in protecting women against HIV. And, so this tells us that these antiretrovirals are highly effective in protecting women. This should give us confidence that a range of methods available to women, could really turn the tide on HIV infections, particularly in young women.
So, this breakthrough is really pat on the back for Wits and recognition of the leading role it is playing in HIV research in the world?
Yes, and what I like to remind people is that, this was the work of many people both globally and across the continent. The HIV Prevention Trials Network has obviously played an incredibly important role. For Wits, it has been important that we’ve had this trial led by women and my co-chair is also a woman, women from the continent. At times in the trial, it was incredibly important to reflect the voices of the people who would use these products. Women and women from Africa had to reflect the context in which these products would be delivered, so that we make sure that they are able to eventually reach the people who need them.
This was a study focused mainly on younger women. Are you going to expand the cabotegravir injection to other groups?
This was a trial in women aged 18 to 45, of which 57% of the trial population was 25 or younger. So, they were largely young women. There are some additional studies in adolescents that are aimed at collecting safety and acceptability data in a population under the age of 18. That’s because we know, that women as young as 15, may be at risk for HIV.
So, it’s important that we have that additional data when we go to the regulatory authorities. There have also been similar trials in cisgender men and transwomen with very similar results. We hope the data, of men, women and younger populations, can be used for registration and it will be possible to deliver the product to the people who need it.
You stopped what’s called the blinded phase of the study. What does that mean?
There is an independent data and safety monitoring board. That’s an independent group of experts whose task is to monitor the trial in terms of its progress, its conduct and the safety of participants. They review the data on roughly a six-monthly basis and they had reviewed the data in May, when the sibling study in cisgender men was stopped for benefit. They reviewed again in November and saw was an obvious trend of benefits in the people who had the cabotegravir. The benefits exceeded statistical significance and it was now in the interests of participants to potentially have access to that product. They recommended that we unblind, that we inform participants of the results, and that we work towards potentially offering those people who were on the Truvada trial, the potential to switch to cabotegravir.
What will happen to the women in this study, now? Will they all be getting this preventative injection?
There’s obviously a process. I know everyone is excited and there’s a huge desire to make everything happen rapidly, but there are a number of steps that we have to follow. The first thing is, we have to understand the few infections in the cabotegravir trial and we have to understand what the drug concentrations were, what the HIV resistance patterns are, so that we can counsel women about their choices when they have the potential to accept cabotegravir.
So, our next steps are really, first of all, to let people know about their study trial, but to also ask them to continue in the study. Once we’ve gone through the changes necessary to offer participants cabotegravir, including access to study medication, we then go through a process to offer people in the Truvada study, the potential to switch to cabotegravir.
We’re interested in, in this open label phase, in the preferences and choices that people make about access to these products. It’s really important to emphasize that we are not interested in pitting one prevention method against another. What we want, is to expand the range of prevention options for women and understanding how people make choices about which medicines they want to use.
We also need to understand, in an open label environment, what this means when women become pregnant and also of ongoing HIV prevention effects. For us, it’s incredibly important to keep the study going, and to keep following up participants. It also ensures that participants can have some post-trial access and reap the benefits of access to prevention, while the much longer processes for licensure and registration and potential access to these products, takes place.
If the injection is such a game-changer, when would this product be available?
Well, that is the big question, and it’s not entirely in the hands of the researchers. The next steps that we understand from Viiv Healthcare who make cabotegravir, is that they hope to submit a licensure package to the U.S Federal Drug Administration (FDA) in early 2021. If they get an expedited review, that would mean that they have a response from the FDA by the end of 2021, which would allow launch in 2022.
That’s the FDA and we obviously want registration in African countries. Those timelines may take a little bit longer and there’s also work to be done with the World Health Organisation and other normative agencies to develop guidelines on implementation issues, particularly in resource-constrained settings. Once there’s licensure, work needs to be done at country-level to negotiate price and access. That’s going to be the work of many people to ensure we can ultimately realise the success of this product for the women who need it most in the countries where HIV is a significant burden.
What is the cost of introducing the CAB-injection (cabotegravir) into South Africa and if this could be rolled out widely, could it lead to a saving for the fiscus as it would mean less people on lifelong anti-retroviral treatment that is paid for by the state?
That’s a great question. And again, we’ve got no sense yet of what the cost will be. There’s discussions to model the potential introduction of an injection into a place like South Africa. It was part of the calculus that a country, like South Africa with one of the largest antiretroviral treatment programs in the world, it’s not sustainable to keep putting people onto treatment.
Treatment is lifelong. It’s a significant cost to the public fiscus and we need to invest in prevention. So, that was one of the reasons why we introduced oral prep into the public sector. The idea that an injectable, which is going to be more effective in preventing HIV, certainly suggests that it would be an important addition to our fight against HIV. But more analysis and more data will be forthcoming around the sort of precise estimates around cost and impact.