AmfAR funds 'bold' viral eradication studies

Edwin J. Bernard
Published: 04 July 2006

The American Foundation for AIDS Research (amfAR) have announced that they are funding a dozen different studies that explore the eradication of HIV from the body. The studies include further investigation into the potential of valproic acid in flushing out HIV from viral reservoirs, as well as several novel explorations of viral and host factors affecting HIV latency and control. One of the grant recipients, Dr Paul Bieniasz, of the Aaron Diamond AIDS Research Center in New York, who will utilise genetic engineering to create viral latency in the test tube, said that "amfAR's decision to pursue viral eradication is a bold one."

Current drugs may be able to reduce HIV to 'undetectable' levels in the blood, they cannot remove HIV's genes that are integrated in the DNA of our own cells. Although scientists have been working on eradicating HIV from the body for more than a decade, and knowledge is increasing incrementally, their work has ultimately been disappointing.

It has now been established that a small proportion of HIV-infected cells do not die, but become dormant all over the body in places known as 'sanctuary sites' or 'viral reservoirs', which include lymph nodes and lymphatic tissue; the gastrointestinal tract, from the tonsils to the rectum; the central nervous system; the thymus, where T-cells are educated, mature and multiply; and the testicles.

"The problem of viral reservoirs is a truly daunting one and research on strategies for eliminating viral reservoirs is clearly essential," . Dr Robert Siliciano, of Johns Hopkins University, told AIDS Treatment Update earlier this year. Dr Siliciano was one of the scientists who discovered viral reservoirs in the mid-1990s. "Even if a cure cannot be achieved," he adds, "understanding viral reservoirs can contribute to the management of HIV infection."

Last year, a small proof-of-concept study by Dr Jean-Pierre Routy, of McGill University Health Centre in Montreal, Canada, which showed that valproic acid may be able to flush dormant HIV out of these viral reservoirs, created much excitement. Dr Routy has received an amfAR grant to extend the study in order to pursue more in-depth analyses of the effects of valproic acid on different types of infected immune cells. Comparisons will be made between cells collected from the blood and gastrointestinal tract, and between cells that have copies of the virus integrated into their DNA and cells with virus outside the DNA.

Other eradication studies funded by amfAR include:

  • genetic mutations in long-term HIV controllers. Do certain mutations prevent HIV from replicating, and can replication-incompetent HIV be created?
  • understanding gastrointestinal tract reservoirs. How HIV infects gut immune cells and why current anti-HIV therapy does not affect gut HIV reservoirs.
  • the role of dendritic cells in HIV infection. Do they promote latent infection of other immune cells?
  • HIV and the brain. Measuring brain function before and after anti-HIV therapy; crossing the blood-brain barrier in order to eradicate HIV in the brain.
  • understanding SIV reservoirs in monkeys. Why do some Chinese rhesus macaques not progress to simian AIDS and what can we learn from this?

"A quarter-century of dashed hopes make even the most optimistic scientific minds reluctant to imagine a body free of HIV," notes amfAR's research programme director, Dr. Rowena Johnston. Indeed, Dr Siliciano feels there is a long way to go before any of these studies - or others - bear fruit. "We have been working on this problem for ten years and have made no real progress," he told ATU. My feeling is that [the eradication of HIV] will not be possible in the next 10-20 years."

However, Dr Johnston believes funding this kind of research is necessary and important. "In terms of what is considered achievable, the climate is beginning to change in AIDS research," she says. "While it is important that scientists continue to pursue new ways to halt viral replication and devise new therapies to treat infected people, the need to actively investigate how to rid the body of HIV once and for all has finally been introduced as a reasonable goal for the epidemic's second quarter-century."

Community Consensus Statement on Access to HIV Treatment and its Use for Prevention

Together, we can make it happen

We can end HIV soon if people have equal access to HIV drugs as treatment and as PrEP, and have free choice over whether to take them.

Launched today, the Community Consensus Statement is a basic set of principles aimed at making sure that happens.

The Community Consensus Statement is a joint initiative of AVAC, EATG, MSMGF, GNP+, HIV i-Base, the International HIV/AIDS Alliance, ITPC and NAM/aidsmap
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