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A recent small scale study – carried out on cultured cells – offers tentative hope of one day being able to ‘activate’ latent HIV so that it can be totally eradicated from the body.

While current HIV treatment regimes – collectively referred to as Highly Active Antiretroviral Therapy (HAART) – are generally extremely effective at bringing the virus under control and reducing viral loads to undetectable levels, HIV still remains inside apparently healthy cells. These cells provide HIV reservoirs inside the body, meaning that despite being brought under control the virus is never eradicated. Should HAART be stopped, these reservoirs ‘activate’ and release more virus into the body. Such reactivation is what leads to the reappearance of HIV in patients who have undergone bone marrow transplants.

However, if these reservoirs could all be somehow ‘activated’ on demand, the virus hidden in latent cells would be released. This would allow other treatments and the individual’s own immune system to remove the remaining HIV from the body, resulting in a true cure. Hope that this can be achieved comes from a recent study reported in PLOS Pathogens which investigated how two drugs affect cells infected with HIV.

Researchers applied the two drugs – PEP005 and JQ1 – to both cultured cells and the extracted blood of individuals with HIV. They found the two drugs worked together to activate latent HIV within the cells; “We are excited to have identified an outstanding candidate for HIV reactivation and eradication” said lead author Satya Dandekar.

One of the drugs – PEP005 – is already licensed in the United States for skin application as a cancer treatment. This means that getting the drug into clinical trials should be relatively easy.

However, while these findings are encouraging, a number of caveats need to be borne in mind.

First, although this drug combination was effective in activating HIV reservoirs, this is useless as a treatment unless the released virus can be effectively destroyed. Commented Dandekar, “we must help patients clear these reactivated cells. Just reactivating the HIV from latency won’t be enough”. Additional studies to develop different drugs will be needed to make this a viable treatment option.

Second, HIV reservoirs can be distributed widely throughout the body in different organs and tissues, and drugs are often not available to all parts of the body equally – if at all. As this was a study performed on cells outside the body, it’s impossible to know for sure how effective the drugs will be in accessing all the areas they need to access.

A related problem is that to truly eradicate HIV, all reservoirs must be destroyed. If the virus persists in just a few cells, they could reactivate.

Only by conducting further trials in animals and eventually humans will these final two questions be answered. Sadly, treatments which appear promising in cell culture studies often turn out to be dead ends once it comes to real world humans. While this study offers a degree of hope, it must be hope tempered by this unfortunate reality.

Phil Hoggart Header

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