Romas Geleziunas has been working in HIV research since the mid-80s, when HIV infection invariably led to AIDS and death, and he believes the development of effective HIV treatment is one of the standout achievements of modern medicine. “Technologically it’s an amazing story,” says the senior director of biology at Gilead Sciences – a biopharmaceutical company – and world leading developer of HIV therapies. “HIV was identified in 1982. By the mid-80s, the first antiretroviral drugs had already started to materialise. Then in the 90s the combination therapies arrived and by the mid-2000’s, HIV could be treated with one tablet once a day. We’ve moved from the virus being a death sentence, to a situation where for the vast majority of people who can access treatment, they can wake up in the morning and manage their condition effectively.”
While a single tablet is a far less demanding regime to follow than the multiple doses a day required of the first HIV patients back in the 90s, antiretroviral therapies only prevent an active virus from copying itself and spreading throughout the body. They do not cure the infection altogether, and patients must continue to take those medicines.
Adherence is the number one mission in HIV treatment,” Geleziunas explains. “If patients do not take their medication every day, they can develop viral resistance, which can basically render that regimen useless. As a result, potential treatment options begin to diminish.” At the same time, providing access to these treatments around the world has been a public health success story. Today, it is estimated that nearly 21 million people living with HIV are accessing antiretroviral therapy globally, with the majority living in low and middle-income countries. According to Sarah Fidler, professor of HIV medicine at Imperial College London, this progress is thanks to a combination of international co-operation and dedicated funding from organisations such as the Global Fund and PEPFAR. Most important, she says, is to continue to sustain that strong political will, in order to bring treatment to the many millions still in need.
From a research perspective, the ultimate aim is to find a way to remove the virus from the body altogether. The challenge is that while HIV typically hijacks the cellular machinery in a person’s immune system in order to copy itself, the virus may also lay dormant inside certain cells as well. These reservoirs of latent HIV can linger for the lifetime of a patient and they are extremely difficult to detect. At any time, cells in the latent reservoir can become active again and start making more HIV. “Getting rid of these viral reservoirs is the central issue,” explains Geleziunas. “If we could eradicate these, we could potentially achieve a cure.”
The most promising approach, according to both Geleziunas and Fidler, is what is known as “kick and kill.”
“The ‘kick’ is a compound that reactivates the latent virus to make it show itself,” Geleziunas explains. “And the ‘kill’, for example, are antibodies that engage the exposed infected cells and attract immune cells to kill them.”
In research supported by the Bill & Melinda Gates Foundation and presented at a recent scientific meeting, scientists from the Beth Israel Deaconess Medical Center showed that 45 per cent of monkeys infected with a virus very similar to HIV, and treated with two of Gilead’s investigational agents, a TLR7 agonist and an antibody, were able to prevent the virus from rebounding in their blood once antiretroviral therapy was withdrawn. Gilead will test these in clinical trials and is funding research at Aarhus University in Denmark to test similar agents in human trials.
While a search for a cure continues, scientists are also focused on longeracting antiretroviral therapies which could be injectable. “The next frontier,” Geleziunas says, “is to get to a point where patients could have an injection just two, maybe four times a year, rather than daily treatments.”
“Nowadays, HIV is a treatable and manageable disease for many like me,” says Winnie Ssanyu-Sseruma, an international development consultant who has lived with the disease for 30 years. “As long as I take my treatment properly, I should not have to worry about spreading the disease to other people. However, the epidemic is not over and there is still a need for this continuing research.”
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