Why we need more women in HIV cure trials

As the search for the elusive cure for HIV continues, researchers must take a lesson from the humble car safety airbag. Just like the airbag, HIV impacts women differently to men.

The well-intentioned scientists who first developed the airbag initially tested it against crash test dummies based on the “average-sized male”. In the real world (which, *gasps*, includes women), these airbags did not provide enough protection. HIV also affects women differently to men.

There are multiple reasons why HIV infection in women is different. These reasons include different anatomy, microbiome, genetics, immunity, and epigenetics. The most outstanding difference, however, is that the innate immune response in women is stronger against HIV than in men. This could explain why women are more likely to be elite controllers (people who can keep HIV suppressed in their blood without medication) than men. And what’s even better than an elite controller? That would be an exceptional controller. Exceptional controllers can not only keep their HIV suppressed without medication, but when scientists study their immune cells, they can’t find any intact virus able to replicate. Very few people living with HIV, including women, are exceptional or even elite controllers. Globally, there are only two reports of exceptional controllers known as the San Francisco patient and the Esperanza patient – and both of these are women!

However, the importance of women in HIV cure research does not stop there. Women have, on average, lower levels of HIV in their bloodstream than men. Women also have lower levels of HIV able to replicate in their body. Despite this, women and men progress to advanced HIV at the same rate. It is unclear why this lower “dose” of HIV leads to the same outcome in women, and this is yet another reason why women being part of all HIV research is critical.

Another very important difference between men and women is that many vital protective immune system functions are coded on the X chromosome (women have two of these, men only have one). Normally, in women, one of these chromosomes is silenced – but there is increasing evidence that parts of the X chromosome can “escape” silencing. And here may lie the hidden key to unlocking a cure for HIV. But without women included in trials, we may never know.

But it is not just HIV cure trials where women need to be involved. HIV treatment trials need women participants too. While HIV treatments seem to be equally effective in men and women, women are more likely to experience side effects of antiretroviral medication. These side effects can also manifest more severely in women. For instance, women experience, on average, higher levels of weight gain on antiretroviral medication than men. Women also experience a greater risk to their cardiovascular and brain health from HIV compared to men. Another possible explanation for these differences might be that women have different levels of hormones, in particular, the sex hormone oestrogen, to men.

By analysing the effect of HIV on women, and in particular these elite and exceptional elite controllers, we have the opportunity to learn so much about HIV.

Currently, women make up less than 17 percent of HIV cure trial participants. Some studies report this number as low as 6 percent. We need to do better than the inventors of the airbag, who only started using crash test dummies resembling women in 2011. We need to recognise the unique insights women living with HIV have in the HIV cure space and call for equity in research. We urgently need to address the imbalance in representation and change the way we design cure trials so that 50 percent of participants are women. This is the only way to ensure that when we find a cure for HIV, it will be a cure for everyone.

Mihiri Weerasuria is an infectious diseases doctor at Monash Health and is studying her PhD in HIV cure with a focus on improving engagement of women in research.

Heather Ellis is a woman living with HIV, is the communications and engagement coordinator with Positive Women Victoria; a member of the HIV Cure Consortium Community Advisory Board; a board member with the International Community of Women Living With HIV – Asia Pacific (ICWAP); a member of the National Network of Women Living With HIV Australia; and a published author.