As we progress towards 2030, the goal post for UNAIDS’ 95-95-95 targets, it is becoming increasingly evident that in order to advance efforts against HIV we need to take an equitable approach that supports all people living with HIV across all demographics. Inspired by this, Dr Cristina Mussini and I revisited our discussions around Real-World Evidence to delve deeper into the importance of representative research for HIV treatment to ensure challenges faced by marginalised groups can be reduced.
Transcript of the conversation
Please note that this transcript has been edited for clarity
VV: Dr Vani Vannappagari
CM: Dr Cristina Mussini
VV: Greetings everybody, I am Vani Vannappagari, Global Head of Epidemiology and Real-World Evidence at ViiV Healthcare. It is my pleasure to discuss the critical and important role that real-world evidence plays in the overall data generation aspects of research in HIV and antiretrovirals with Dr Cristina Mussini. Cristina – hello! It’s a pleasure to talk to you again. Could you please introduce yourself for our audience?
CM: Hi Vani, it’s a pleasure for me to speak to you too. I am Cristina Mussini, I am Professor of Infectious Diseases at the University of Modena and Reggio Emilia in Italy, I’m also a member of the governing board of EACS for about 20 years, and I’m a member of the governing council of the International AIDS Society, so HIV has been my main field of interest for all my career, I have to say.
VV: Cristina, we have just had the IDWeek and HIV Glasgow, two premier conferences where we saw a great amount of real-world data presented. We saw data from studies that looked at effectiveness, safety, patient-reported outcomes, all of them on antiretrovirals and across numerous populations in real-life clinical settings, including women, adolescents, people aged 50 and older, and some data on minorities. So, tell us why studies like these are so important?
CM: I have to say that in most of the cases when we talk about randomised clinical trials, for many reasons, one is that you have to enrol patients in a very short period of time so it’s very difficult to select people from different populations – you just enrol the ones that fulfil the inclusion criteria. The other thing is that usually they enrol the ‘blond, blue-eyed perfect patient’, and in our clinic this isn’t what we really see – only a minority of people have these ‘perfect criteria’; usually they have to deal with people with comorbidities, with older ages, with many other problems that are excluded from clinical trials.
VV: Which then leads me to the next question – yes, we do try to include women in clinical trials but generally it is much lower than what we see with respect to participation of men, especially white men, in these clinical trials. So, women living with HIV, and especially those of post-menopausal age, don’t have a whole lot of data to help them decide what would be the best treatment strategy for their health – so, what do you think the role of real-world evidence can be in changing this?
CM: I have to say that what you are saying is really, really important because in some switch studies, some switch clinical trials we have seen a percentage of women, around 26-27%, so there is attention by pharma companies in including women in studies. The problem is that when we look at treatment-naïve populations and those who are at risk, really we see women very rarely at our latitude. So that’s why if we collect data from different approaches with women, we can compare them and we can see what could be the best care for women, post-menopausal but also younger women, adolescents and teen women, who acquire HIV vertically.
VV: That brings me to our next population, very important. These are the children and adolescents living with HIV. Given that there are an estimated 2 million young people living with HIV across the globe1, how can real-world studies be used to support treatment decisions for this population?
CM: I really think that having core data from this population is crucial. Because if we go outside of Africa, for example, all centres are following a small number of this group, fortunately, because vertical transmission in high-income countries is now very, very low, so it’s important that we put together the data. Now, one of the things we have to understand is about breastfeeding. It’s not possible to conduct a randomised clinical trial on breastfeeding, especially at our latitude – it would be impossible. But also, while in some countries and in all the guidelines, we say if a woman wants to breastfeed, we have to perform tests on the baby every month we have to follow the woman. Putting together all this data can give the possibility to have evidence that we could also use in our clinical practice.
VV: Let me briefly touch on clinical trials, because for all new ARVs, clinical trials are the starting point. And we have been scrutinised for only recruiting participants matching certain criteria, and predominantly they are white men. But if clinical trials need to progress to include more women living with HIV, more minority groups and more marginalised groups, i.e. people who have not traditionally been part of clinical trials so far, what is it that we as researchers across multiple groups can do to make clinical trials be more representative of the population living with HIV, and how can real-world evidence help us in doing that?
CM: The question is very important, because if you ask yourself a question like this, you mean that this is a relevant programme. And also the fact that, for example, the FDA or EMA now need data on women means that it’s something that is there. Everybody understands this. But what is possible is to go where these minorities are. For example, conducting a study on transgender people in Thailand or in Malaysia would be very important, because to conduct a study on transgender people in Italy would be very complicated. This is really a population that we don’t see, they are hiding. Very, very rarely we see them. And they don’t have a network like gay men. We could gather data on drug-drug interactions or hormone replacement; now that there are injectables, it would be important to see if it’s possible to give these drugs to transgender people and see the effect of silicone, for example. I think that we should go and look for these minorities and these populations where they are.
VV: Cristina, it has been such a pleasure. The two of us could spend the whole day talking and I feel like we have only touched the tip of the iceberg. There is so much more we could continue to discuss and this is only the treatment, we have not even touched prevention so maybe that is something for a future discussion. So, do you have any last thoughts?
CM: You are the head of ViiV’s epidemiology and real-world evidence function – what are you as ViiV doing to address the issues relating to women, minorities and paediatric populations?
VV: We have a diversity and inclusion initiative specifically for addressing participation and representation of women and minority populations in clinical trials, through which we are aiming to get enough women and minority groups for meaningful analysis of clinical trial data so that when the drugs are coming to the market, we will have data for most of the groups, and where we have data gaps, we can identify and proactively put together real-world evidence study plans and we conduct those studies throughout the lifecycle of the drugs. That’s a really important piece. The second one that we are also doing is, when it comes to pharmacovigilance and especially focusing on the paediatric population, we are now working and in discussion with multiple stakeholders across the spectrum, especially working with our partners at the PENTA Foundation who, as you know, are the experts on paediatric studies, and also some collaborators in sub-Saharan Africa, so we are generating data that will help the paediatric population in their treatment choices. And finally, I do want to mention that ViiV now has a framework for accelerating data generation in clinical trials for ARV use in pregnancy also. So, there are multiple initiatives across various groups within ViiV that we are continuing to push forward to make sure that there is not only representation in clinical trials but also representation in how we conduct our real-world evidence, and focusing data generation in the groups that are traditionally not the focus of research. All in all, we are hoping that for all the newer ARVs we are bringing to the market, we will have much more data accessible to HCPs like you.
CM: That would be fantastic Vani because we have fantastic drugs, and really no one should be left behind. I really believe this, so it’s our duty to reach everybody and to have evidence for everybody.
VV: On that note, thank you Cristina. It’s always a pleasure to talk to you.
CM: For me too Vani, thank you very much.