7/30/2019 HIV Reservoirs and Viral Eradication Workshop to Reach HIV Cure

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HIV Reservoirs and Viral Eradication Workshop to Reach HIV Cure

The advent of combined antiretroviral therapy (cART) 15 years ago has dramatically changed the

outcome of HIV infection from a deadly to a chronic disease. However, patients still experienceproblems of compliance, resistance, toxicity and cost, as these therapies are not available worldwide.

If plasma viremia can remain under control (undetectable) in the majority of patients taking seriouslycART, HIV remains in hidden reservoirs allowing viremia to rekindle within a few weeks each time

therapy is stopped.

Over the past few years major advances have been made in understanding the nature and persistence

mechanisms of these reservoirs. It is currently believed that HIV remains latent in some memory T

cells, which have a very long life span. This reservoir of a few million cells in the body is considered asthe major obstacle towards HIV eradication in treated patients.

However, if a decade ago almost nobody dared to speak of curing HIV infection, scientific advanced

have allowed developing potential strategies for a cure, some of which have already reached clinical

trials.

This renewed optimism has been spurred by 3 clinical observations:

1-The Berlin patient:This case has been widely reported. It involves a man who developed acute leukemia during the course

of HIV infection and received bone marrow transplant from a donor with a genetic mutation that

protects against HIV infection. With now more than 5 years of follow-up, this patient is off cART andhas not experienced viremia rebound or immune deterioration.

2-The Mississippi child

Reported in early 2013, this case was born from an HIV-infected mother who was not followed, andconsequently not treated, for her infection. HIV infection was documented at birth in the child and

cART started as early as 31 hours after delivery. One year later, the mother and the child were lost of

follow up. When there were seen again in the clinic, the child was 23 months of age and had stoppedcART for at least 5 months. Unexpectedly, no detectable viremia was found in blood by using the most

sensitive assays, and the child was even seronegative for HIV.

3-The VISCONTI cohort

This French cohort (for Virological Sustained Control after Treatment initiated at acute Infection) has

collected 14 patients who were treated very early after HIV infection, for an average duration of 3years, and still have undetectable viremia despite cART cessation for an average duration of 7 years.

Although their body still harbor potentially replicating HIV, the virus remains under control without

drugs. The mechanisms of this functional cure remain unclear, but this situation could concern 10-15

percent of patients treated at acute infection.

What the first 2 cases show is the limits of our current biological tests to define a sterilizing cure. This

situation would be the total elimination of HIV from an infected person. However, the majority of HIVDNA integrated in cells is defective and unable to replicate. Therefore, a sterilizing cure is not

necessarily a situation where traces of HIV cannot be found. And this is the case in the Berlin patient

and the Mississippi child where, using the most advanced technology, traces of HIV could be found, insome tests, at the limit of detection of the assays.

These observations are seminal in the search of an HIV cure. Understanding the mechanisms at play

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can be of major importance for the 34 million people living worldwide with this virus.

All these issues will be discussed during the forthcoming International Workshop on HIV Persistence,

Reservoirs and Eradication Strategies to be held in Miami (Fl, USA), 3-6 December 2013. The

advanced program is available at: http://www.hiv-workshop.com

Contact:

Alain LafeuilladeDepartment of Infectious Diseases General Hospital

Toulon, France

Ph: +33 4 94145084lafeuillade@orange.fr

http://www.hiv-workshop.com

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