What’s going on in HIV cures?

 

About The Author

It was on the December 31, while I was looking for a job on the Internet, when my GP phoned to tell me that I was tested positive on HIV. Then I made the most rational decision I had ever made in my life, instead of fall in desperation and despair, I changed my search from jobs to HIV sites. I started to learn about HIV that day, I’m still learning, and I’ve planned carrying on.

I had to attend the classical New Year Eve party that night and I did. It was very hard pretending that everything was right while I had an inner turmoil. I shared my best wishes with everybody while I was thinking: “I’m sick, they aren’t”. As the year was ending and a new year was coming on, my life was changing from past to future.

After a while I changed my mind. Becoming positive was as a door that opened to different horizons in front to me. I crossed the threshold and began to think differently, and to act differently as well. First of all I felt the need to know how would be my future being “positive”. I knew about a lot of researches going on and very much of them are very promising. As I learnt more and more about HIV I got a personal perception of HIV. Now I believe that the first aim of any positive people is to be healthy to receive the new treatments that will be available in the next years. I hope I'll see the end of this movie.

M. Garcia

What’s going on in HIV cures?

Antiretrovirals already reduce HIV to undetectable levels in the bloodstream, even though a person taking the drugs is not cured.

To find lingering virus in a person taking anti-HIV drugs, scientists have to use painstaking methods to collect millions of blood and tissue cells and analyze them for residual HIV. These methods are not practical for use on the general HIV-positive population, particularly since HIV will become rarer and harder to find as methods for eradicating it get better. As a result, many researchers think that HIV cure research will be hampered until a better way of detecting residual HIV reservoirs is found.

It is also possible that it is unnecessary to completely eliminate HIV from the body that reducing it below a certain threshold will ensure HIV cannot rebound to cause a new infection. However, whether this is true, and if so, what that threshold is, are still unknown.

In the meantime, the definition of an HIV cure is likely to follow the path of cancer – people who show no evidence of the disease for a certain period of time, in the absence of antiretroviral drugs, would be declared cured.

Researchers are increasingly turning to the question of how HIV can be cured, or at least put into long-term or permanent remission without antiretrovirals. There are two strategies currently being investigated to cure HIV: sterilizing cures and functional cures. [1]

STERILIZING CURES

The sterilizing cure method aims to eliminate all HIV-infected cells, completely purging HIV from the body.

Sterilizing cure is one that reduces viral loads to less than 1 copy per milliliter of blood, either permanently or for an extended period of time.

The only current example of a sterilizing cure is from a case study of a man with HIV who had acute myeloid leukemia, a form of cancer that starts in the bone marrow.

HIV requires the CCR5 protein, which is on the surface of white blood cells, in order to attach to and infect the cell. People naturally born with an alternate form of the CCR5 gene are almost entirely immune to HIV.

A strategy of using bone marrow transplantation with a CCR5 mutant donor is not a realistic cure for HIV given the toxicity and complexity of the treatment. Additionally, it is still not clear why and

how HIV was eliminated in this patient, although scientists continue to study him.

FUNCTIONAL CURES

A functional cure aims for a remission state and long-term control of HIV, including low viral loads in the absence of antiretroviral therapy.

A functional cure is one that reduces viral loads to less than 50 copies per milliliter of blood, either permanently or for an extended period of time.

One natural example of a functional cure can be found in elite controllers. Elite controllers are individuals infected with HIV whose immune systems are able to naturally control the virus without antiretroviral drugs. These individuals successfully maintain stable CD4 (white blood) cell counts and low or undetectable viral loads.

Researchers are highly interested in further understanding how elite controllers manage HIV and avoid disease progression, since this could help with identification of new methods to treat people with HIV or development of an HIV vaccine.

How to get it?

1.- Using Gene Therapy To Make Cells Resistant To HIV

Gene therapy is an experimental approach that is currently in early stages of clinical testing. Gene therapy involves modifying the genetic information in a cell so that it becomes, for example, resistant to HIV infection.

In most cases, cells are taken from the patient’s body, genetically modified in the laboratory, and then injected back into the patient.

HIV requires the CCR5 protein, which is on the surface of white blood cells, in order to attach to and infect the cell. People naturally born with an alternate form of the CCR5 gene are almost entirely immune to HIV.

Since his transplant, no sign of HIV has been detected in The Berlin Patient.

In one recent high-profile Phase 2 gene therapy clinical trial, HIV-positive people on antiretrovirals were injected with modified immune cells lacking the CCR5 protein. The therapy did not eliminate HIV in these patients, but it did successfully raise CD4 counts in patients whose immune systems had failed to recover after starting antiretroviral therapy.

Another approach under investigation is an RNA-based gene therapy. This strategy works slightly differently but is also aimed at reducing or eliminating CCR5, as well as slowing HIV replication.

Results showed that the treatment was well tolerated and that the gene therapy was successful, although results faded after four weeks. Nonetheless, the study offered a proof-of-concept that RNA gene therapy is possible.

While gene therapy has potential, it may not be particularly practical in the long run. [2]

2.- Therapeutic Vaccines

Therapeutic HIV vaccines work by enhancing the body’s natural immune response, helping to control HIV in people already infected with the virus. This is in contrast to preventative vaccines, which are used in HIV-negative individuals to prevent infection.

Researchers hope that therapeutic vaccines could be used to reduce or eliminate the need for HIV treatment.

Results from two recent studies in Simian Immunodeficiency Virus (SIV)-infected monkeys have been promising. SIV is a retrovirus similar to HIV that infects primates; studying SIV can provide insight into potential therapies for HIV in humans.[3]

A British clinical trial of HIV vaccine demonstrates an approximately 90 percent difference in viral count in HIV-infected people, researchers say.

Gregory Stoloff, chief executive officer of Seek -- a privately owned biopharmaceutical company -- said this is the first time ever that a human immunodeficiency virus vaccine has shown such a meaningful result in a human clinical trial. [4]

3.- Latent HIV Activators

The major obstacle to a cure is latent HIV, HIV that lies dormant during treatment until treatment is stopped. Eradicating latent HIV is a top priority for scientists, and several drugs are currently being tested for their ability to reduce or eliminate this hidden reserve of virus. Since antiretroviral drugs usually work by blocking replication, they do not work on latent HIV.

Zolinza (vorinostat), a drug currently approved to treat a type of lymphoma, shown that successfully activates latent HIV in infected cells in the laboratory. Studies in other patient populations have suggested that Zolinza causes side effects when used long-term, but physicians hope that prolonged treatment with the drug would not be necessary.

Prostratin, a traditional Samoan treatment for hepatitis, also activates latent HIV in the laboratory. Prostratin is still in pre-clinical studies but may be too toxic for use in humans.

Another class of drugs under investigation is DNA methylation inhibitors. This class of drugs is used to treat cancer.

Dacogen (decitabine), a drug approved to treat a group of blood conditions that are often considered cancerous, has been shown to activate latent HIV in cells from people with HIV. Results from other studies showed that Dacogen was more effective when used in combination with prostratin and other drugs.

Finally, researchers are also investigating the protein IL-7, which helps immune cells develop and survive. In a recent study, results showed that IL-7 was well-tolerated, indicating that it may be successfully use to reactivate latent HIV. IL-7. [5]

4.- New Drugs

Researchers at the Massachusetts Institute of Technology’s Lincoln Laboratory have developed and demonstrated a novel broad-spectrum antiviral approach, called DRACO—which stands for double-stranded RNA activated caspase oligomerizer—that may prove to be effective against virtually all viruses, including HIV and hepatitis, according to a report published online by PLoS One. DRACO selectively induces cell suicide, in cells containing any viral double-stranded RNA, rapidly killing infected cells without harming uninfected cells.

In theory it should work against all viruses, says Todd Rider a senior staff scientist in MIT. Mr. Rider began to develop this project 11 years ago. [6]

Unknown Risks: Potential Safety Issues With Current Approaches [7]

Latent HIV Activators

For example, one of the ways scientists hope to cure HIV is by activating latent HIV, HIV that lies dormant during treatment until treatment is stopped. Many of the drugs that are being evaluated as latent HIV activators, including histone deacetylase (HDAC) inhibitors, work by affecting the way cells read and use DNA.

“A theoretical risk of HDACIs [HDAC inhibitors] is that they will induce activation of other retroviruses and/or DNA viruses including cytomegalovirus (CMV), hepatitis B virus (HBV), and JC [John Cunningham] viruses which has been demonstrated in vitro [in the laboratory],” wrote Dr. Lewin and Prof. Rouzioux in their review.

Using Gene Therapy To Make Cells Resistant To HIV

Another treatment that raises cancer concerns is gene therapy. Gene therapy also involves changing the way cells use DNA, often by inserting new genes. If this process does not work as it should – if the new gene is inserted in the wrong place, for example – it can cause tumors to develop instead. This has been observed in some gene therapy trials.

In the most advanced HIV gene therapy trial to date, a Phase 2 clinical trial targeting the CCR5 protein that HIV needs to infect cells, there has been no evidence so far of cancer or other major side effects. However, the researchers will continue to monitor the participants to make sure they do not develop any problems longer-term.

M. Garcia

References

[1] http://www.aidsbeacon.com/news/2011/05/12/advances-and-barriers-to-a-cure-for-hiv-part-1-types-of-hiv-aids-cures/

[2] http://www.aidsbeacon.com/news/2011/05/16/advances-and-barriers-to-a-cure-for-hiv-aids-part-3-gene-therapy-and-therapeutic-vaccines/

[3] http://www.aidsbeacon.com/news/2011/05/16/advances-and-barriers-to-a-cure-for-hiv-aids-part-3-gene-therapy-and-therapeutic-vaccines/

[4] http://www.upi.com/Health_News/2011/07/21/Injectable-HIV-vaccine-shows-promise/UPI-94461311221408/

[5] http://www.aidsbeacon.com/news/2011/05/13/advances-and-barriers-to-a-cure-for-hiv-part-2-targeting-the-latent-hiv-aids-reservoir/

[6] http://www.voanews.com/english/news/health/Drug-Compound-Wipes-Out-Multiple-Viral-Infections-127974633.html

[7] http://www.aidsbeacon.com/news/2011/05/18/advances-and-barriers-to-a-cure-for-hiv-aids-part-4-obstacles-in-finding-a-cure/

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