Anti-ACTH (7-23) (Polyclonal), ALEXA Fluor 594
Helen Bygrave is a GP in London and serves as the Non-communicable Disease Advisor for the MSF Access Campaign.
Swaziland’s results were announced by the director of the country’s antiretroviral therapy (ART) programme at a recent symposium, Fixed dose combination (FDC) pills for cardiovascular disease and hypertension: perspectives and lessons learned from HIV/AIDS and TB, which sought to draw on the experience underlying such successes to tackle the growing public health challenges of CVD and hypertension. In stark contrast to the results seen for HIV, the analogous 90-90-90 figures for hypertension, a disease affecting over 1 billion people globally, portray a far gloomier picture. Global awareness of hypertension is 47%, self-reported use of treatment 37%, and control for those on treatment a mere 14%. Access to treatment for secondary prevention for CVD does not fare any better.
So how could we use the lessons learned from the scale-up of ART to improve programmes for secondary prevention of CVD and treatment of hypertension? One important word that springs to mind is simplification. Many still see treatment of CVD as complex, requiring hospital-level doctors performing individualised fine-tuning of dosage and combination of therapeutic classes. This was the same challenge facing treatment of HIV a decade ago but, through taking a public health approach and working towards treatment optimisation, including the use of fixed dose combinations (FDCs), ART is no longer only for the privileged few who have access to specialist medical care but is available to many of those who need it throughout the developing world.
This was made possible through clinicians and patients alike developing clear requests for researchers and drug developers on how they wanted their treatments to be formulated: one pill, once a day, with minimal toxicity, and in a formulation that could be used across populations at an affordable price. The possibility of a therapy ever meeting their criteria might have seemed far-fetched two decades ago, but today these characteristics are almost taken for granted in HIV programming in resource-rich and resource-poor settings alike. With WHO providing guidance on this optimised first-choice combination, governments have demonstrated the programmatic benefits of simplified procurement, supply chain, storage, and prescriber practice as well as the cost benefits. For the patient, adherence is easier and has, therefore, improved. In conflict and unstable settings where Médecins Sans Frontières (MSF) works, FDCs also provide a simpler option for provision of care when contingency planning is needed. While one size does not have to fit all, this approach allows simplification for the vast majority, with alternatives made available for the minority who have medical contraindications or side-effects.
The other cornerstone enabling scale-up of ART delivery has been the development and dissemination of WHO guidelines on HIV, shaped by public health principles. The HIV community over the last decade has taken an evidence-based but pragmatic approach to introducing ART into health systems that on the surface may have appeared ill-equipped to successfully manage this disease. This has been made possible through simplification of treatment protocols to allow for decentralisation and task-sharing between different cadres of health-care workers.
Given these successes, why not take a similar approach for hypertension and secondary prevention of CVD? The results of the TRIUMPH study, a clinical trial for a low-dose triple combination of telmisartan, amlodipine, and chlorthalidone to treat hypertension, caught my attention earlier this year. In this study, 68% of the cohort achieved control of their hypertension within 6 weeks, with a single, once-a-day combination tablet that was well tolerated. This would leave just 32% of patients in the cohort requiring treatment modifications, potentially placing a simplified, decentralised and task-shared model of care within reach. Could these modifications also be simplified by taking two pills out from the same pot? This would streamline the supply chain, prescribing, and dispensing alike. Likewise, a fixed-dose combination for secondary prevention that is “good enough” to achieve a public health benefit may also alleviate the burden on the health-care worker who currently struggles to prescribe and dispense multiple tablets.
So, are these formulations currently included in the current WHO Essential Medicines List (EML)? To date, the answer is no. The WHO’s Expert Committee on the Selection and Use of Essential Medicines has turned down three successive applications, citing the complexities of clinical management and the challenges of either too many or too few combinations submitted. Without WHO’s guidance on the programmatic use of such combinations, their role in programmes and market potential – even if included on the EML – are not clear.
But what about the patients? I recently spoke with Pambeyi Mbeure, a patient on ART with MSF in Zimbabwe. Pambeyi lives in Chipinge, a rural village where he travels 15 km to his nearest clinic. He is typical of many people living with HIV in that he also suffers from other chronic conditions. In Pambeyi’s case, they are diabetes and hypertension. He told me that he was first diagnosed with HIV in 2006 and that taking just one pill a day has been manageable to control his disease. With the diagnosis of his other conditions in 2016, he now takes a total of 11 pills a day. “I feel like I’m overdosing when I take all these pills – I just want to sleep. I am used to one pill a day for my HIV, why can’t it be the same for these other diseases?”
MSF, the London School for Hygiene and Tropical Medicine, and the George Institute, Sydney, co-hosted this symposium and are now working with stakeholders from the meeting to define how FDCs may support access to treatment for both hypertension and secondary prevention of CVD.