HIV antiretroviral therapy: Getting to the heart of the matter

The HIV landscape has completely transformed since the start of the pandemic. A HIV diagnosis in the 1980s was considered fatal, as people usually progressed to AIDS due to the lack of available treatments. 42 years later, we have an array of different drug options and as a result, people diagnosed with HIV today can now expect to have near-normal life expectancies. Here, Dr Akif Khawaja from the National Heart & Lung Institute (NHLI), highlights the impact of HIV treatment over the last 42 years and how it influences cardiovascular research today.

HIV Treatment: from AZT to U=U

At the start of the pandemic, there were no available treatments. Patients would progress to AIDS and were only offered palliative care. It wasn’t until 1987 that the first antiretroviral drug, zidovudine (AZT), was licenced for the treatment of HIV. A major challenge with HIV treatment soon became apparent, as the virus can rapidly mutate and change its genetic code to become resistant to the drug supressing its replication. This challenge was quickly seen by clinicians as their patients would start to rebound from antiretroviral monotherapy (one drug regimens) as HIV became drug resistant and was able to replicate again. The introduction of combination antiretroviral therapy in 1996 has been monumental to HIV management. A change in treatment guidelines meant that patients who would have previously been given one drug, were now given three drug combinations, each targeting different parts of the HIV life cycle. This approach meant that patients could suppress HIV replication and achieve a sustained undetectable viral load, meaning that the level of virus in their blood is so low, it can no longer be detected by diagnostic tests.

Many studies have explored this undetectable status, two key ones being the PARTNER and PARTNER2 studies. Here, researchers looked at couples where one partner was living with HIV and on treatment and one partner was HIV-negative. Both studies found no HIV transmissions between partners, with the scientists predicting that you would need to have condomless sex for the equivalent of 435 years before you’d see HIV transmission. Studies like these have been vital in demonstrating that when on effective treatment (having an undetectable viral load) you can no longer pass on the virus, which has been central to the Undetectable = Untransmittable (U=U) message.

The Future of Antiretroviral Therapy

HIV antiretroviral therapy continues to be an active area of research. We’ve seen huge progress over the decades regarding both drug burden and drug options. When talking about drug burden, we mean the number of pills needed each day. Early combination therapies required multiple dosing during the day and meant some people needed to take up to 22 pills a day. This number of pills could easily result in pill fatigue and the loss of motivation to take medication. With continued research and development of more effective drugs, patients today can be prescribed single-tablet regimens so only need to take one pill a day to manage HIV.

We are also seeing the development of new therapies. New classes of antiretroviral drugs are undergoing clinical trials to determine their effectiveness. We are starting to see injectable antiretroviral drugs being introduced to clinics, which would remove the need for patients to take daily pills in favour of an injection every two months. This area of research aims to provide patients with as many options to manage HIV and make it as easy as possible to take their medications.

From Bedside to Bench: Understanding Heart Disease in The Context of HIV

The availability of effective antiretroviral therapy has caused a dramatic drop in AIDS-related deaths and an ageing population of people living with HIV, who seem to have an increased risk of heart disease. Why this is interesting from a cardiovascular research point of view is that we have a growing population of people exposed to long-term antiretrovirals, but have very little understanding how this exposure might impact the risk of heart disease.

Here at the NHLI, the Emerson group has been working to understand how antiretrovirals impact this risk of heart disease by looking at how antiretroviral drugs influence cells of the cardiovascular system. We have shown that some commonly prescribed drugs alter endothelial cell (the cells lining the veins and arteries that regulate blood pressure) and platelet (the cells responsible for clotting and heart attacks) behaviour. We have recently been awarded a British Heart Foundation-funded project grant to take this work further, and look at how platelets behave in people accessing HIV treatment at clinics within Chelsea and Westminster Hospital NHS Foundation Trust. We hope that this work will help us better understand how certain antiretroviral drugs change platelet behaviour and if certain drugs could be increasing the risk of heart disease. We hope that through this work, clinicians will be able to provide personalised approaches to managing heart disease in people living with HIV, by tailoring antiretroviral therapy to minimise cardiovascular risk.

Dr Khawaja is a Research Associate in the Cardio-Respiratory Interface section of the National Heart and Lung Institute (NHLI).

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