Latest news with #SayeKhoo
Medscape
7 days ago
- Health
- Medscape
What Comes Next After Failure of Injectable HIV Medication?
While the injectable HIV treatment regimen cabotegravir/rilpivirine (Cabenuva) is an increasingly important option, including for people who have struggled with adherence to daily tablets, it comes with a caution that must be discussed with each patient. Around 1.5% of people who switch to the injections experience virologic failure, often despite perfect adherence to the injection schedule. While this rate is not higher than for daily oral HIV regimens, failures are frequently accompanied by resistance-associated mutations. Since cabotegravir is an integrase inhibitor — as are dolutegravir and bictegravir, the most frequently used anchor drugs in modern HIV treatment — the development of resistance to integrase inhibitors risks significantly limiting future HIV treatment options. Virologic failure on cabotegravir/rilpivirine is therefore considered 'a low incidence, but high consequence event' (a phrase shared by Saye Khoo at the Conference on Retroviruses and Opportunistic Infections earlier this year). But there is limited data and a lack of guidance on the most effective regimens to use following failure associated with resistance. 'In reality, what people do in case of failures with cabotegravir/rilpivirine is that they base their therapy on genotypic results,' explained Pierre Giguère, MSc, clinical pharmacy specialist at the Ottawa Hospital, Ottawa, Ontario, Canada. 'We like to go with agents for which there are no mutations that could predict treatment failure. And in situations with cabotegravir/rilpivirine, when you have dual-class resistance mutations, like in our cases, what's left are the protease inhibitors.' The protease inhibitor darunavir — typically boosted with cobicistat or ritonavir — has become 'the pillar of therapy' in these situations, he said in an interview. However, he and his colleagues reported an unusual case series of six patients at the International AIDS Society Conference on HIV Science this week. Each one was successfully treated with bictegravir/emtricitabine/tenofovir alafenamide (Biktarvy), a single-tablet daily regimen based on an integrase inhibitor. All patients had major mutations associated with both integrase inhibitors and non-nucleoside reverse transcriptase inhibitors. Despite this, all achieved viral suppression to below 20 copies/mL after switching to the bictegravir-based regimen and have maintained this for between 6 and 18 months. This approach emerged unexpectedly during clinical practice. The first patient was a woman who initially chose to switch to the bictegravir-based regimen because she could not tolerate the pain she experienced at the injection site. However, samples taken at the time of her switch subsequently revealed that she had a virologic breakthrough with resistance to integrase inhibitors (148R) and reverse transcriptase (101E). Given that this regimen would not normally be recommended in these circumstances, her clinicians considered taking her off the bictegravir she had already started but decided against it as she was now virally suppressed. 'What would be the motivation to change therapy in a patient who is currently on a simple regimen that is working?' asked Giguère. 'So, the decision was to keep following this patient closely, making sure that she remains suppressed. And that was our patient zero.' The next five patients to go on the regimen were the next five patients to experience virologic failure on cabotegravir/rilpivirine at the hospital. 'We decided just to keep going with the Biktarvy, based on that n of one experience, which ended up being an n of two, and now is an n of six,' Giguère said. Three of the subsequent patients had mutations at both positions 138 and 148. While cabotegravir frequently selects for these mutations, and they rapidly confer a significant loss of susceptibility to cabotegravir, that is not the case for bictegravir. 'From an in vitro perspective, you would not suspect that these mutations would much impact bictegravir susceptibility,' Giguère said. 'But what has been lacking has been clinical data.' Laura Waters, MD, consultant physician in sexual health and HIV medicine at Central and North West London NHS Foundation Trust, London, England, described the approach as 'brave.' She noted that while other cases of patients switching to integrase inhibitors after failure of cabotegravir/rilpivirine have been reported, they did not generally involve people who had integrase inhibitor resistance mutations. 'But as we're learning more and more, resistance isn't absolute, and both our second-generation integrase inhibitors have high inhibitory quotients, and so we would expect that virologic suppression would be possible for many individuals,' she told Medscape Medical News. She said she would be worried about the durability of the response. For three of the five cases reported, follow-up was for less than 1 year, while the patient observed the longest had 20 months of follow-up. 'The concern is around forgiveness: What happens if somebody misses a dose? What happens if somebody takes a cation-containing treatment or supplement that reduces integrase concentrations further?' For his part, Giguère stresses the importance of defining a safe approach that can be implemented when virologic failure on cabotegravir/rilpivirine occurs. 'I think we have to be able to come up with a simple, well-tolerated backup regimen in the case of failure,' he said. For the moment, it's not clear that the bictegravir-based regimen is the right one, but he hopes other clinicians will try to replicate the experience. 'Time will tell if the effect is long-lasting, and we need more people to confirm it.' The study received no funding. Giguère reported having no relevant financial relationships. Waters had received speaker and advisory fees from Merck Sharp & Dohme (MSD), ViiV Healthcare, Janssen Pharmaceuticals, and AbbVie. She is also an investigator on trials funded by Gilead Sciences, MSD, and ViiV Healthcare with funding provided to her institution.
Yahoo
25-04-2025
- Health
- Yahoo
Uni study trials new treatment for deadly disease
A clinical trial of a new treatment for one of the world's deadliest parasitic diseases is under way in Liverpool. Visceral leishmaniasis is a neglected tropical disease found in parts of Asia, East Africa, and Brazil, and is transmitted through the bites of infected sand flies. It causes flu-like symptoms including fever, fatigue and weight loss, and is almost always fatal if left untreated - but has been the subject of limited research in recent years. Current treatments require daily injections for up to 17 days which can cause pain, nausea and vomiting, and the new study is trialling an oral drug that could overcome these barriers by being easier to store, transport, and administer. The trial is a collaboration between the University Hospitals of Liverpool Group (UHLG), the University of Liverpool and the Drugs for Neglected Diseases initiative (DNDi), a medical research non-profit organisation. It is being conducted at the Royal Liverpool University Hospital. Professor Richard Fitzgerald, principal investigator of the study, said: "Visceral leishmaniasis claims thousands of lives every year, and current treatments are often inaccessible to those who need them most, particularly in low-income regions where healthcare systems are limited. "This trial offers hope for a more practical and effective solution, one that could reach those most at risk and save countless lives. "It also reflects the skills and expertise here in Liverpool, showing that we are at the forefront of developing new medicines for a disease that affects people on the other side of the world." The trial is currently recruiting volunteers from Liverpool and the surrounding areas, with several participants already having completed a screening process. It will take place over two weeks, with volunteers closely monitored by clinical specialists. Fellow researcher Professor Saye Khoo added: "We aim to develop a treatment that can be stored in varying conditions, delivered directly to vulnerable communities, and administered easily, without the need for hospitalisation." Dr Fabiana Alves, director of leishmaniasis programme at the DNDi, said: "An estimated 50,000 to 90,000 new cases occur every year – most of them in Eastern Africa, where half of those infected are children under 15. "We urgently need better, effective, safe and patient-friendly medicines, and this trial in Liverpool is playing a critical role toward that goal." Listen to the best of BBC Radio Merseyside on Sounds and follow BBC Merseyside on Facebook, X, and Instagram and watch BBC North West Tonight on BBC iPlayer. You can also send story ideas via Whatsapp to 0808 100 2230. One drug is 'new hope' for three killers Urgent action needed as malaria resists key drug The Liverpool team preparing for future pandemics University of Liverpool University Hospitals of Liverpool Group Drugs for Neglected Diseases initiative
BBC News
25-04-2025
- Health
- BBC News
Liverpool University study trials new treatment for deadly disease
A clinical trial of a new treatment for one of the world's deadliest parasitic diseases is under way in leishmaniasis is a neglected tropical disease found in parts of Asia, East Africa, and Brazil, and is transmitted through the bites of infected sand flies. It causes flu-like symptoms including fever, fatigue and weight loss, and is almost always fatal if left untreated - but has been the subject of limited research in recent treatments require daily injections for up to 17 days which can cause pain, nausea and vomiting, and the new study is trialling an oral drug that could overcome these barriers by being easier to store, transport, and administer. The trial is a collaboration between the University Hospitals of Liverpool Group (UHLG), the University of Liverpool and the Drugs for Neglected Diseases initiative (DNDi), a medical research non-profit is being conducted at the Royal Liverpool University Hospital. 'Save countless lives' Professor Richard Fitzgerald, principal investigator of the study, said: "Visceral leishmaniasis claims thousands of lives every year, and current treatments are often inaccessible to those who need them most, particularly in low-income regions where healthcare systems are limited."This trial offers hope for a more practical and effective solution, one that could reach those most at risk and save countless lives."It also reflects the skills and expertise here in Liverpool, showing that we are at the forefront of developing new medicines for a disease that affects people on the other side of the world."The trial is currently recruiting volunteers from Liverpool and the surrounding areas, with several participants already having completed a screening process. It will take place over two weeks, with volunteers closely monitored by clinical researcher Professor Saye Khoo added: "We aim to develop a treatment that can be stored in varying conditions, delivered directly to vulnerable communities, and administered easily, without the need for hospitalisation."Dr Fabiana Alves, director of leishmaniasis programme at the DNDi, said: "An estimated 50,000 to 90,000 new cases occur every year – most of them in Eastern Africa, where half of those infected are children under 15. "We urgently need better, effective, safe and patient-friendly medicines, and this trial in Liverpool is playing a critical role toward that goal." Listen to the best of BBC Radio Merseyside on Sounds and follow BBC Merseyside on Facebook, X, and Instagram and watch BBC North West Tonight on BBC iPlayer. You can also send story ideas via Whatsapp to 0808 100 2230.
