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Modern drugs are very effective in managing HIV infection but are unable to provide the cure. Some recent developments target the issue at the core of this problem. This allows to hope that curative drug for HIV is only few years away.

Human Immunodeficiency Virus (HIV) is behind the largest and deadliest pandemic in the recent human history. In 2011, 34 million people were living with HIV worldwide.

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In our age of advanced medicine, the situation when infectious disease spreads seemingly out of control is very rare. For the majority of common infectious diseases we have either medicine capable of curing them, or at least, medication making them manageable. Also, preventive measures such as vaccinations allow to put most infections under control.

Neither cure nor vaccination is developed for HIV so far.

But effective therapeutic management is now available. HAART (Highly Active AntiRetroviral Therapy) helps to eliminate the most of virus from the body of infected person, thus reducing to the minimum his or her chances to develop AIDS and suffer any other infection-related health problems. In fact, people receiving the antiretroviral therapy can now expect to live almost normal life, and their average life expectancy is almost the same as in the healthy population.

Advantages and problems of modern antiretroviral therapy

Modern drugs effectively reduce the level of virus in the blood (viral load) to almost undetectable level. The decrease in viral load not only improves the immune system of the patient but also decrease the risk of HIV transmission to healthy people.

The price to pay - take a pill every day. Like any other chronic disease, HIV needs to be treated by drugs on a daily basis. And there is always a danger of developing drug resistance thus making the medicines ineffective. On top of this, drugs do have both short-term and long-term side effects that in some cases can be severe.

Finally, the newest and most efficient drugs are costly and often unaffordable. The price of unsubsidized drug bill can easily reach $30,000 per year.

The problems of living with HIV make the development of cure very desirable. Lots of research is being done worldwide in the pursuit of this goal. But how achievable is this target? Can we expect any real breakthrough that is so eagerly anticipated by millions of infected people?

Although modern HAART therapy is hailed as a great success, the cure of HIV remains an elusive goal. There were, however, several reports of so-called functional cure of HIV infection in several individuals.

One HIV-positive patient received the bone marrow transplant from a donor with a rare natural genetically programmed resistance to HIV infection. The monitoring of this patient so far did not reveal any signs of disease return. He was declared completely free from HIV thus making him the first ever person to be cured of the disease.

Another very recent report described the case of a newborn baby who got infection from mother. Therapeutic intervention with HAART has started almost immediately after the baby was born and seemed to be successful in completely elimination of virus.  

Obviously, the above strategies are not viable for the overwhelming majority of patients. Something else has to be done.

Complete cure for HIV is difficult but not impossible to achieve

The problem lies with the mechanism of drug action: all modern drugs are active only against the actively replicating virus.

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When virus is inactive (dormant), the drugs have no possibility to kill it. Virus plays “hide and seek” with antiretroviral drugs.

The virus does become silenced in some situation. For example, the host cells of immune system can become dormant and shut down almost all replication mechanisms. In such cells virus can stay without showing any activity for very long time. As a result, this virus remains completely insensitive to all drugs. Once the cell wakes up, the virus starts to reproduce as well and easily replenish its population in the body if the drugs were discontinued.

There are also so-called anatomical reservoirs of the virus. HIV can hide at different anatomic locations such as gastrointestinal tract and brain of the patients receiving antiretroviral therapy. These sites have various kind of barriers limiting the ability of antiretroviral drugs to reach the infected cells. Again, when the treatment is stopped the virus from these places could cause re-infection.

Some researchers hypothesize that HIV can infect certain non-immune cells and survive there in dormant stages for many years.

Addressing the problem of latent viral pool

The logical answer to the problem of latent viruses lurking somewhere in the safe heavens around the body is to get them out of their hiding places. Two major strategies are currently being developed by researchers working in this field.

First strategy aims to activate the latent cells of immune system. Activation would also turn on the replication process of the virus .With the virus replicating inside the cell, the cell will ultimately die, and the released viruses could be get rid of using the traditional and highly effective antiretroviral therapy.

There are different agents which could potentially help in activating the latent T cells. One such agent, Interleukin-7 (IL7) is currently undergoing clinical trials. Prostratin is another compound that could do this but at present time only limited data is available for its safety profile and efficiency in humans. It will take several years to get enough data and see if these drugs serve the purpose.

The second strategy relies on turning on the HIV genes within the latent cells infected by virus. Histone deacetylase inhibitors (HDACI) seem to be able to do exactly this. These drugs could turn on the gene expression in the viruses present inside the silent T cells thus making them vulnerable for antiretroviral drugs. Further studies are needed to evaluate the efficiency of these drugs.

With the pace of developments in the HIV research, many scientists now believe that the cure for HIV is only few years away. The infection has already proven itself as a very difficult target to treat. Many drugs previously developed with curative intent have failed to their promises.

But this time the level of confidence among scientists and observers is higher than ever. Let’s hope that they are right.

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  • Stephen J Kent et al. (2013) The search for an HIV cure: tackling latent infection. The Lancet Infectious Diseases 13, 614-621
  • Shay Matalon et al. (2011) Histone Deacetylase Inhibitors for Purging HIV-1 from the Latent Reservoir. Mol Med. 17(5-6): 466–472
  • Sharon R. Lewin (15 June 2013) A cure for HIV: where we've been, and where we're headed. The Lancet 381, 2057 – 2058
  • Gabriel M. Ortiz et al. (1999) HIV-1–specific immune responses in subjects who temporarily contain virus replication after discontinuation of highly active antiretroviral therapy. J Clin Invest. 104(6): R13–R18.
  • Photo courtesy of Gates Foundation by Flickr : www.flickr.com/photos/gatesfoundation/5659545732/
  • Photo courtesy of Wheeler Cowperthwaite by Flickr : www.flickr.com/photos/wcowperthwaite/5774727034/

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