The short answer is ‘no’, despite the clamour of contending priorities that make personal health sometimes seem not worth the bother.

The recent fifth episode of the Women up to Know Good webinar series, “PrEParing for Change: The future of HIV management within a changing landscape”, discussed why the fight against HIV is far from over. It also revealed how innovations such as the GIFT (Genital Inflammation Test) can be used to detect inflammation associated with HIV and STI risk, and how choice and pre-exposure strategies are crucial safeguards.

To mark World Aids Day on 1 December, the GIFT team at the University of Cape Town (UCT) brought together two science rockstars who may make you consider starting a fanzine and even question your decision to leave X.

Professor Linda-Gail Bekker is director of the Desmond Tutu HIV Centre and CEO at the Desmond Tutu Health Foundation, and has published more than 700 peer-reviewed papers. Dr Dvora Davey is an associate professor at the University of California and an honorary associate professor in epidemiology at UCT.

Their message is the need for choice to maximise the impact of HIV prevention.

And they’re not talking about Choice, the Health Department’s rebranded condoms launched in 2004. In those days, the message was “Khomanani” (caring together) and the choice was simply: “Wear a condom or risk infection.”

Thankfully, 20 years later, there’s more choice around HIV prevention. This is particularly liberating for women who previously had to put their sexual health in the hands of a man’s willingness to use a condom. The reality is that women need more agency because, as Davey says: “Every week about 4,900 young women become infected, and girls 15 to 24 are twice as likely to be living with HIV than men. In South Africa we have the largest HIV epidemic in the world and women and girls accounted for 64% of all HIV in the last year.”

The high incidence of HIV among women inspired the GIFT team to develop a device that detects vaginal inflammation. The Genital Inflammation Test (GIFT) aims to identify inflammation associated with asymptomatic inflammatory STIs and bacterial vaginosis in women. Genital inflammation increases HIV risk in women, so testing for this identifies HIV risk. Davey sees GIFT as a useful tool: “I think GIFT can potentially serve as a point-of-care tool to flag women who may benefit from targeted PrEP (pre-exposure prophylaxis) strategies. Our team is currently exploring integrating GIFT into antenatal or reproductive health services and how this could significantly enhance our ability to prevent new HIV infections and protect mothers and their infants.”

Intervention and prevention of HIV infection are particularly important for pregnant and breastfeeding women because they are two to four times more likely to acquire HIV and there’s also a substantial risk of vertical transmission to their infant.

Why are pregnant and breastfeeding women more susceptible to HIV?

Davey attributes several biological and social factors that make pregnant and breastfeeding women more susceptible to HIV. Biological factors include hormonal changes, STIs, pregnancy-induced immune adaptations, macro and micro postpartum trauma to the vagina, and breastfeeding. Social-behavioural factors include the reduced likelihood of using a condom, sexual networks, stigma, IPV (intimate partner violence) and substance use.

In eastern southern Africa one in four infant infections with HIV is attributed to new maternal HIV acquisition. Davey emphasises: “If you only remember one thing today, it’s that we cannot effectively eliminate vertical transmission of HIV without addressing the incidence of HIV… So just by treatment alone, we will never be able to reduce and eliminate infant HIV.”

Navigating and managing HIV risk

Women need access to options to manage their HIV risk. Davey’s suggestion for pregnant and breastfeeding women is: “We need to do both primary prevention, which is preventing women from acquiring HIV during pregnancy and breastfeeding, and secondary prevention, which is getting women to take their antiretrovirals to become virally suppressed during pregnancy and breastfeeding.”

Fortunately, a recent groundbreaking study on subcutaneous lenacapavir could be a big weapon in the HIV prevention arsenal. The Purpose One and Purpose Two studies involved more than 4,000 young women (16 to 20) and among those who received subcutaneous lenacapavir over one year, there were just two infections. When Bekker presented the findings at the 2024 Aids conference in Munich she received a standing ovation, and the general mood was resolute optimism. At that moment there was a sense that HIV/Aids could be put to bed (literally and figuratively) and, “now we can move on to climate change”.

And of course, it’s difficult not to be jazzed about subcutaneous lenacapavir – the results of the Purpose One and Purpose Two studies are extremely exciting. However, Bekker and Davey agree that overenthusiasm is premature. Bekker reminds us: “I want to just temper that enthusiasm a little bit to say I think we do still need to think about bringing everything we know about primary prevention on board.”

Nevertheless, what Bekker calls a “prevention train” is a massive step: “Any method of prevention can roll up at your carriage in your station that may be applicable for you, and that might vary from time to time, depending on where you are.”

What are the PrEP choices and what role can GIFT play?

For most women, the primary concern is the safety of taking PrEP, and if they’re pregnant or breastfeeding, for the safety of their baby. The next worry is the side-effects. Both concerns can be mitigated with effective counselling from a clinician or medical professional. The third concern is stigma, and this is where the type of PrEP can make a big difference. Typically, daily PrEP pills are not very discreet, and this is one of the reasons pill adherence drops among women. Injectable PrEP is often preferable because you can get it privately at a clinic. However, they can result in pain or swelling. Whatever your preference, the overarching message is that if you’re at risk of HIV, any PrEP is better than no PrEP.

Oral PrEP is available to all South Africans and there are options. For example, TDF tenofovir and FTC is a well-established oral PrEP that’s effective if you take four tablets a week. Oral TDF/FTC is also effective as an event-driven protocol (taken around sex events) and this has been tested on men. Although event-driven protocols for TDF/FTC haven’t been tested on women, there are guidelines and recommendations. Currently, there’s work being done on a dual-purpose pill that combines oral contraception and oral PrEP and there’s also much anticipation around a new monthly pill called MK 8527.

The monthly dapivirine ring and the longer-acting DapiRing are vaginal rings to prevent HIV. Research on a fast-dissolving vaginal insert and a dapivirine vaginal film are also being trialled.

And then there’s One Ring to rule them all… The OneRing vaginal insert has two compartments, one each for contraception and HIV. They can be self-inserted, and the inserts can be changed as needed. There’s also a rectal douche with tenofovir for those having anal sex.

Cabotegravir, a long-acting two-monthly injection, works for men who have sex with men, transgender women and women who have sex with men. There’s also an ultra-long-acting version in the pipeline.

The big excitement, of course, is lenacapavir, the six-monthly subcutaneous injection. It’s currently undergoing approval from regulators and the other big news is that the Purpose One study shows that it is safe in adolescence, pregnancy and lactation.

The GIFT team plans to trial the device for PrEP adherence and uptake as well as in pregnancy for better birth outcomes.

More options and better coverage mean better efficacy

Options give us power and agency. However, the next crucial phase is access and roll-out. And, when it comes to roll-out, Bekker and her team are on a mission. They are getting PrEP into communities through mobile clinics, local clinics, schools, courier services, youth clubs and quick PrEP depots.

However, as we know, “all people” never really means all, and pregnant women are frequently left out of the equation. This is remiss given that globally there are about 213 million pregnancies each year and according to the World Health Organization (WHO) about 21 million of these are girls between 15 and 19.

Why do we need to include pregnant women in research?

Again, this comes down to choice and in the past five years there has been a shift to view pregnant women, not as a vulnerable group, but as a complex one. Davey asserts: “Instead of protection from research, what we want to advocate for is protection through research… And instead of presumptive exclusion, we want fair inclusion and informing women about availability of research studies, including implementation science studies, that are ongoing around PrEP.”

In a recent study, Davey says oral PrEP is safe to take while pregnant and breastfeeding, and this is extended by the findings around lenacapavir in the Purpose One study. Furthermore, in 2017 the WHO recommended that all women, including those who are pregnant and breastfeeding, should be given the choice to take PrEP. In South Africa, recent policy changes have meant that pregnant and breastfeeding women who were previously excluded from PrEP guidelines have been included. The GIFT team has also just submitted a new proposal to test the device in a randomised control trial with more than 8,000 pregnant women in Zimbabwe.

Bekker and Davey are staunch advocates that pregnant and breastfeeding women become part of PrEP implementation because of the double prevention benefit of mother and infant. Women now have an informed choice, based on clinical trials, which is based on the high risk of contracting HIV versus the low risk of taking PrEP.

Promoting prevention

Bekker’s image of a prevention train is loud and proud. It’s a symbol of groundbreaking science, national pride around HIV research, and the power of choice.

When HIV hit a crisis point in South Africa in the mid-Nineties it was seen as a death sentence and the response focused on the male condom and abstinence. A magic pill was just an idealistic dream. It’s worth pausing on the reality of having options that allow us to take control of our own sexual health and wellness and manage HIV risk.

As society, it’s our duty to encourage HIV prevention through choice promotion, education and communication. Everyone should know about PrEP, and because it’s only as effective as it’s used, we need to influence the perception around it. The reality is that we need to actively promote it because, according to Nora Rosenberg’s recent study, to get a quarter of a million infections diverted in our region, we need to offer PrEP to 26,000,000 adolescent girls and young women. The GIFT device can also be used as a valuable tool to indicate risk associated with vaginal inflammation and could lead to an increased uptake of PrEP.

And, as to when we’ll get broad access to lenacapavir? Well, a lot depends on Gilead Sciences, the production of a generic version, and government funding. But, Bekker has made it quite clear: “I won’t rest until it comes to South Africa.” And that’s a promise we can all stand behind. DM

Jaqui Hiltermann writes for Jive Media Africa, the communications partner of the GIFT project.