Hiv Reservoirs - control or Cure Is an urgency

Current Haart (highly active antiretroviral therapy) regimens for Hiv infection requires life-long supervision of drugs. This implies long term adherence, toxicities and cost. Despite these combinations, Hiv persists in "viral reservoirs" and each time therapy is stopped, the infection rekindles. New therapeutic approaches are mandatory to target these viral reservoirs and allow one day an Hiv drug-free remission. First, we need to good study the mechanisms complicated in Hiv persistence and then screen new drugs capable to reach the virus in its latent state and anatomic reservoirs where Haart does not have good diffusion. Some scientific breakthrough have already been obtained over the last 2 years, making the hope for a 'cure' no longer a dirty word... We have launched a scientific society to boost this study with the target of seeing a cure in the next decade.

The most common want for anything and any country that is dealing with the spread of the Hiv virus is a cure for those infected and a vaccine to preclude it from spreading. We want to understandably eradicate the disease off the face of the planet much like what has been fulfilled, with Small Pox on a world wide scale today. Unfortunately it is easier said than done in today's global environment. But not all hope on seeing a cure is lost.

Hiv Antiretroviral Drugs

In fact, we are much closer today than we have ever been before. The cost of treating those infected with the virus are huge. The antiviral drugs used in the treatment are highly expensive and with the new recommendations from Who, treatment in a whole of countries of the world is started much earlier. This is greatly increasing the cost of treatment worldwide because more people infected with Hiv are seeking this helpful treatment earlier in their disease. This fact alone makes a cure even more needful for us to find. The burden of treatment cost for each personel infected with Hiv is astronomical. Some estimations of pharmaceutical treatments are a high as ,787.00 per year in the United States which is more than a lot of people's annual salaries in that country. As scientists complicated in the study of Hiv reservoirs for more than 10 years, we call for an international, coordinated force, to decipher the last mechanisms of Hiv persistence.

Hiv Reservoirs - control or Cure Is an urgency

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Hiv Reservoirs Part 5: Purging the Hiv reservoir

As Hiv persists in latently infected T cells in patients on long term antiretroviral therapy (Art), one strategy to flush out this residual Hiv disease is to activate and "purge" the Hiv reservoir.

In vitro support

Hiv Antiretroviral Drugs

Several experiments in cell lines models of Hiv latency have in case,granted information on the mechanisms involved in the maintenance of Hiv latency. One of the most studied mechanism is histone deacetylation. Several compounds called Histone Deacetylase Inhibitors (Hdaci) have been shown capable to wake up Hiv in vitro from its latent state. The strategy is, therefore, to use such compounds in aggregate with Art, in order to safe uninfected cells, and activate latently infected cells and let them die of this productive infection.

Initial Disappointment

The first attempts at activating residual Hiv disease from its latent forms were unsuccessful. Use of cytokines, like Interleukin-2, or Okt3 antibodies, led to a broad activation of the immune system, like a cytokine storm, which was toxic for the patient with no convincing proof of any Hiv stockroom decline. Valproic acid is an agent used against epilepsy that has Hdaci activity. Combined to Art and a fusion inhibitor, T-20, it was initially shown to be able to cut the Hiv reservoir. However, subsequent studied were unable to confirm these preliminary results. It was then demonstrated that this Hdaci was weak and, in particular, not exact of the type of Histone Deacetylase involved in Hiv latency.

New Drugs on the Horizon

With a great characterization of the Histone Deacetylase sub-types, Several compounds have been screened with promising activity. One of then is vorinostat, or Saha, which is already on the shop for a rare kind of hematopoietic malignancy. However, other issues are slowing testing of this drug to purge the Hiv reservoirs, which are more ethical than scientific. The dilemma is to use potentially toxic drugs in patients on long term Art which are well and live general lives...

There are other molecules able to reactivate Hiv in vitro that act via other pathways than histone deacetylation. Such a aggregate is Prostratin. Although its improvement was initially impaired by the fact that it was extracted from a rare plant, its chemical synthesis has been thriving and will allow clinical testing in protocols.

How to Move Forward?

The next urgent step is to test these potentially "purging" drugs in animal models of Hiv infection. Several macaque models are available, which reflect both the establishment of Hiv reservoirs and anatomic compartments. There is some concern that these purging approaches would be too potent in sanctuaries like the brain where Art diffusion is impaired.

Once animal models will have validated the approach, small pilot studies in humans will be mandatory.

There is a possibility that Several agents will have to be combined or sequenced to reactivate the Hiv reservoir, as some molecules will act on some cells and others in other subsets of the reservoir.

A large international plan is needed to coordinate this research.

Hiv Reservoirs Part 5: Purging the Hiv reservoir

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Hiv Reservoirs Part 7: New Biological Tools

As antiretroviral therapy (Art) is able to block viral replication, more sensitive tests than those used in the clinic are vital to quantify the viral reservoir and assess the action of new eradication strategies. First measures of latently-infected cells used cell dilution techniques which are time appealing and wish a large quantity of blood. Pcr techniques allow to test smaller samples with better sensitivity.

Ultra-sensitive Plasma Viremia Assays

Hiv Antiretroviral Drugs

Hiv Reservoirs Part 7: New Biological Tools

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