Editor's Note: Pediatric care and treatment for children with HIV infection have always been a critical component in the global fight against AIDS. Recently, at the AIDS2024 conference, Dr. Anna Turkova from University College London shared her insights with Infectious Diseases Frontier(IIDF) on the breakthrough advancements in pediatric HIV care. She highlighted that the detection and diagnosis of undiagnosed children with HIV remain a major challenge that requires ongoing effort and investment. While the use of dolutegravir-based triple oral therapy has led to significant success in treating pediatric HIV, the development and application of innovative therapies such as long-acting injectables are still in progress. Additionally, psychosocial support is crucial in pediatric HIV care. Looking to the future, Dr. Turkova envisions long-acting injectable preventive treatments, painting a hopeful picture for the global pediatric HIV care landscape.01
IIDF: Could you elaborate on some of the most exciting breakthroughs achieved in recent years in paediatric HIV care that you find particularly noteworthy?
Dr Turkova: The most exciting breakthrough I think is access to a very effective treatment. For many years, and even still now, children are left behind in terms of the best treatment available for them. One of the studies we have done, that has been done for a decade, has been evaluation and continued development of a pediatric formulation of drugs called dolutegravir. Dolutegravir, not only alone but as dolutegravir-based treatment, is now currently one of the most effective treatments. I am really pleased that we have contributed to the rollout with our study, other studies and, of course, a huge amount of joint effort from all the different stakeholders. At the moment, there are 95 countries where 99% of children living with HIV reside can procure and are procuring dolutegravir. We have already seen a better virological response and we know that work has been worth it, however, there is still a way to go. It is a good oral treatment. We know resistance is developing, so we will need a good second-line. We also know that lots of children and adolescents have problems and difficulties with adherence, so novel methods of delivery, like injectables, are needed. Access to a good second-line therapy, particularly tenofovir alafenamide, is challenging, because there is no generic formulation, and access to the long-acting injectables is not approved yet, and there is no clear plan. So there is still a way to go in terms of achieving the same treatment outcomes as in adults, which means achieving 95% biological suppression and treatment. We have a gap there. I think the most significant gap is for us to find the missing children, because that gap is unknown. A lot of children out there have not been diagnosed, therefore we cannot start them on treatment and save their lives. There is a high mortality rate in the first few years of life. As I quoted in my Plenary speech, the peak of mortality happens in the first month if a child is undiagnosed, and 50% will die by two years of age if not diagnosed. The problem is that another 50% will survive and may not have symptoms. There is a myth that children with HIV need to be ill but many of them are not sick and have no symptoms. To find those children and have a strategy for where and how to test many people, and overcome stigma and discrimination of people coming forward to test their children, and governments not contributing financially – that is the problem. This is the biggest gap – finding undiagnosed children.
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IIDF: Early diagnosis of HIV infection in children is crucial for timely treatment and improved outcomes. What are the major challenges we face currently, and what innovative diagnostic tools or methods are being developed or already in use in clinical practice to address these?
Dr Turkova: There has been a lot of effort and a lot of different initiatives ongoing across the world, exploring different ways and different modalities. Currently, there is a very nice document produced by UNICEF that is a technical brief on finding undiagnosed children. The Global Alliance has aimed to end pediatric HIV, signed by twelve African countries, also highlighting that finding children is one of the main strategies towards ending HIV in children.
There are lots of interesting modalities. It depends on the country’s epidemiology. It depends on a country’s HIV prevalence. It depends on the age of estimated distribution of undiagnosed children in that country. So countries need to know their own epidemiology, and then they can combine different modalities to ensure resources are used wisely. You can test children in high income countries in pediatric clinics, along with TB and malnutrition, but also have access to emergency wards and casualty departments. If a child comes in with a broken arm and nothing to do with HIV, if you still test, it has been shown to have a high yield for picking up children who have no symptoms yet, therefore giving the option for an early diagnosis. If you diagnose them when they already have symptoms of advanced HIV, the outcomes are poor, mortality is high, and recovery is not that great. So we try to pick them up before developing symptoms. The other modality is to diagnose children though the family index case findings. For example, if an adult is diagnosed with HIV, we ask if they have children in the family, and then try to reach out to those children, and try to persuade adults to test children. Even, for example, if there are families that look after children who are orphans, they are at high risk because there is the potential that their parents died with HIV and that is why they are orphaned. So it is important to know your community situation, and know how to read that community and use the community knowledge to reach out to these sometimes hard-to-reach populations and families. There are well child clinics. I explained in my Plenary, that around a quarter of new mothers will acquire new HIV during pregnancy or while breastfeeding, so even if you test mothers during pregnancy sometimes you might still be missing quite a few who acquire HIV during the last trimester of pregnancy or during breastfeeding. So we can pick up cases by testing in so-called well child clinics. When a mother brings a child in for vaccination, for example, or medical checkup, we should check a mother’s status if she doesn’t know her status already, and then pick up an infant potentially at risk. If the mother is not around, and a carer comes, you could get consent to test the infant. That is for younger children, under one year or two years old, because these are the ages that tend to be seen at well child clinics.
We know the majority of undiagnosed children are well over 2 years of age and 60% are aged above 5 years. So how do we pick up those children? That is a big question. That is why community input is really important, and getting testing done through the community services. There was an interesting project in Zambia, for example, where they were developing a pilot for doing HIV tests as a requirement for preschool, so as a medical examination and part of medical assessment, HIV could be tested. They don’t need to disclose the result of the test, but there is a way to say this child was tested. I understand this hasn’t been piloted yet, but the idea was developed. For adolescents, for example, different ways might be through reproductive health clinics, or through male circumcision clinics, or any other health services. They can integrate HIV testing through any health services that adolescents are attending. Apart from health services, you could reach them through social networks, through their peers. There is also mobile testing as well.
There are many interesting initiatives ongoing that are showing promise. So I think we are living in a very interesting time. We know we have a lot of tools that can work. We need more implementation to indicate which approach in which country works best. We need to encourage that, and of course, funding is important.
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IIDF: Regarding pharmacotherapeutics, what are the latest advancements in treatment regimens for paediatric HIV-infected individuals? Particularly, those aimed at simplifying treatment, reducing side effects, and enhancing the quality of life for these children.
Dr Turkova: For the public health approach, we need to understand that the pediatric population is very small compared to adults. If you start to introduce an individualized approach, it is very difficult to then deliver that approach consistently when reaching out to all children in rural and urban settings and so on. We really need a more universal regimen that works for all. So far, it is a triple oral therapy, dolutegravir-based triple therapy. What simplification means is that there is a tablet combining the three agents into one. We call it pALD – pediatric abacavir/lamivudine/dolutegravir. It is a triple fixed combination which provides the preferred recommended pediatric treatment regimen for first-line. This simplifies treatment for healthcare professionals, because the dosing is very simple – you adjust the number of tablets according to weight band. It is simpler for carers because they don’t need to have 2 or 3 bottles at home and to remember how many of each tablet is needed. It is one bottle, one label. Much fewer errors. We think this is the best way to go – a fixed dose triple combination that we know works very well for the majority.
We are also evaluating dual treatment. It has been shown that this works very well for adults as a simplification for virologically suppressed adults and also as first-line starting therapy for adults. There is a study called D3 – D stands for dolutegravir, 3 stands for 3TC. It is dual – two drugs in one. It is a randomized controlled trial comparing triple dolutegravir to dual dolutegravir in children who are virologically suppressed. The idea is, first of all, it is a smaller tablet; and secondly, it is one drug less, which potentially leads to better safety in the long term. This study is ongoing. It is nearly completely recruited. We will hopefully be presenting the results in 2026.
Of course, we are very much looking forward to injectables in children, because a lot of families have issues with adherence and difficulties in giving in oral tablets every day. I think it will work, especially for the families having difficulty administering medicines every day. But we don’t have them yet. The studies are ongoing evaluating this, but it will still be a bit of a wait to ensure they are accessible for most kids. There is actually quite a long way to go.
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IIDF: Apart from pharmacotherapy, how do you view the role of psychosocial support in paediatric HIV care? Are there any successful case studies or programs that you can share to demonstrate the significance of psychosocial support for HIV-infected children and their families?
Dr Turkova: In my Plenary, I said that treatment alone is not enough. We see it again and again. When I was trained and learned how to treat and manage children with HIV, the treatment is the simplest thing out of everything else. Everything else is much more difficult. We have shown again and again that without actual psychosocial support, outcomes are not great. We see this starting from an early age. If you start treatment early, there is a little bit of benefit from early treatment. There is less mortality with early treatment, but the benefit disappears, because most of the families involved come from vulnerable backgrounds, and without extra support with nutrition, with livelihood, with food, with adherence support, with supporting the mothers, there are mental health issues, addressing domestic violence, addressing the living environment, the treatment alone is not enough. You need to provide support to keep these kids alive. Even once starting treatment, the mortality is still very high by two years of age.
There have been studies, for example, SEARCH Youth, which was a randomized cluster trial looking at non-therapeutic, so non-treatment, intervention. What they found was there are four components to these interventions. The first component was discussion about life events that young people want to talk about, the important things that happen in their lives. It is not about adherence to ART. It is about what is happening at home, what is happening in college, a recent marriage, a recent broken relationship. The program gives you a structure for what to cover, how to prepare questions, and then to focus on those questions. This improves the rapport between the adolescent and the healthcare provider, and his been shown to improve retention in care. It has been shown to improve virological suppression, because being engaged and understood can translate into being better with your medicine. Especially, this has been shown to lead to higher rates of re-engagement for those who might be lost to follow-up. It has also shown to have lower symptoms and signs of depression, which is really important for mental health. So yes, that is one the real examples you asked about. It is not my trial, but one of my favorite trials.
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IIDF: Looking into the future, what is your vision for the development of paediatric HIV care? What are the most significant changes or breakthroughs you foresee in this field in the coming years?
Dr Turkova: First of all, my dream is that long-acting injectables be available for prevention for women of reproductive age who are at risk in high prevalence countries in order not to acquire HIV. And for pregnant women in particular, because they are at high risk. For infants for postnatal prophylaxis, we are far away from being there, but potentially we could be looking at twice yearly injections. This is when many cases, nearly all, are getting infected, during pregnancy and breastfeeding, with a little transmission occurring through other routes (healthcare settings, horizontal transmission, sexual abuse). It is mostly mother-to-child transmission, what we call vertical transmission. Prevention is about protecting mothers and then protecting infants during breastfeeding. We would only need 2 or 3 injections to cover the breastfeeding period, but that is when it would have the most impact. Many adolescent say they need a choice. Probably not 100% will say they want injectables, because some people may not like injectables. Many say it is just too difficult to take tablets every day. It is a problem that their tablets remind them of their HIV status. For adolescents finding out about their diagnosis, it takes time to accept their diagnosis. You need time, and oral daily treatment is a reminder. There is also a stigma. You see your friends, you are going out, having sleepovers and attending parties – you don’t want to carry your tablets around. It is a way to provide them freedom. So long-acting injectables are the way to go, especially for those who can make that choice. This may help a lot of people. If you really want to achieve targets and end pediatric HIV, we need these new modalities. I hope that we could find every single child who is yet undiagnosed to make sure there is an option for them to be on treatment. I would like to have really successful effective prevention that doesn’t depend on people taking oral drugs. Twice a year injections would be fantastic. Choice for adolescents is very important. They really want the long-acting injectables. We will see it. It will be nice to see more new ideas and more implementation.
