Some HIV patients can live a healthy and drug-free life controlling the infection on their own. Who are they and how they do what they do?

On October 2015 Robert Gallo’s team from the Institute of Human Virology, University of Maryland, is going to launch the phase I clinical trial for his first HIV vaccine.

HIV (Human Immunodeficiency Virus) attacks the immune system and weakens our defence by causing a strong loss of immune cells called CD4+ Lymphocytes, thus leading to AIDS (Acquired Immune Deficiency Syndrome). The obtainment of an effective vaccine would be a landmark progress in the battle against HIV. It would mean to be able to eradicate the virus for good rather than just “keep it quiet”.

Unfortunately, the truth is that after a 15-years preclinical study, Gallo’s vaccine has still a long and arduous way to go before it can be approved.

But how are HIV patients currently treated and how do they respond to therapies? While I was researching about it, I came across something that deeply caught my attention and tells us about how our body can be unpredictable and sophisticated.

Few people know that apart from the majority of patients, there are two rare classes of them that seem to be able to suppress the virus and live a healthy life without taking drugs for several years. These people are called Post-treatment Controllers and Elite Controllers.

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Chart displaying all the antiretroviral drugs available in the UK grouped in different classes. Each class of drugs attacks HIV in a different way. Generally drugs from two or (sometimes three) classes are combined together to ensure a powerful attack on HIV. From the booklet of anti-hiv drugs, aidsmap.com

 

Normally, HIV patients must undergo a chronic antiretroviral therapy (ART) to reduce the level of HIV in the body and help the immune system to work properly. That means that they have to take several drugs, that attack HIV virus in different ways, combined together for their entire lives.

Last summer, Asier Sáez-Cirión, an epidemiologist from the Pasteur Institute in Paris, reported about a French girl that is alive and healthy twelve years after HIV treatments that she had started at birth were stopped. The girl is not cured, HIV DNA has been found in her immune cells, but the virus is at undetectable levels in her blood. How is it possible? No one knows.

What is known is that she is not alone. Sáez-Cirión himself published a paper in 2013 describing 14 patients, known as the Visconti cohort, which, like the French girl, underwent an ART shortly after HIV infection and remained healthy for several years after they ceased their treatments. These patients have been included in the class of Post-treatment Controllers and today there are 20 of them.

Elite and Post-treatment Controllers have a quite similar condition that paradoxically seems to derive from opposite genetic backgrounds. Elite Controllers have high levels of CD8 lymphocytes, cells that eliminate HIV infected cells, which gives a hint on why their immune system is so effective. On the other hand, Post-treatment Controllers seem genetically less protected. Their genetic background predisposes them to a weak immune response to the virus. The immune system rapidly deteriorates and high virus levels are detected shortly after infection.

As explained on Science, Sáez-Cirión depicts three possible alternative causes. These patients are maybe helped by their innate immune system that could work together with the ART, quickly started after the infection, in limiting the HIV reservoirs (HIV viruses accumulated inside infected cells). Another hypothesis is that post-treatment controllers could have been infected with a weaker mutant form of the virus. To me, the most interesting one is that this particular weakness could help them limit the size of the reservoir before the drugs are even started.

The existence of these patients tells us something about how important a prompt therapy-based response after a HIV diagnosis can be. Since the achievement of a vaccine is still far, collecting a clear and vast knowledge of cases and genetic backgrounds seems the best way to go. Elite and Post-treatment Controllers show us how deeply significant this goal is and how complex and unpredictable the body’s response to HIV can be.

Header image: Scanning electron micrograph of HIV-1 budding (in green) from cultured lymphocyte. From wikimedia commons.