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The road to HIV cure; exploring HIV functional cure

Written by  Winnie Agnes Botha

As the world all over is looking forward to a day when scientists will announce that finally there’s a permanent HIV and AIDS cure, scientists at the HIV Research for Prevention Conference-HIVR4P- in Madrid Spain, present evidence that shows how difficult it is to get a permanent HIV cure at the moment.

Ananworanich: Copies of the virus hide in reservoirs Ananworanich: Copies of the virus hide in reservoirs
25
October

Although a number of cure strategies are under investigation today in different parts of the world, a sterilizing cure, to completely eliminate HIV in a human body, seems to be difficult to achieve.


Dr. Zaza Ndhlovu, an Instructor in Medicine at Harvard Medical School, argues that this is difficult because of how HIV behaves in humans.


“The virus makes different copies of itself, attacks the CD4 cells and imitates the CD4 cells to get into all parts of the body even into places where it cannot be eliminated,” Dr. Ndhlovu said.


According to Ndhlovu, there are parts of the human body where the virus hides after replicating itself and imitating the human immunity cells and in these parts the human immune system the virus is very safe and cannot be eliminated.


The deadlock of permanent HIV cure “hits at this point, how to get rid of the virus reservoirs and there´s no clear way to measure the amount of HIV reservoirs,” Ndhlovu said.


Understanding the HIV reservoir

Jantanat Ananworanich of the US Military research program describes the viral reservoir as copies of the virus which are hiding quietly in different areas of the body.


“These copies are sleeping and hidden and they can´t be fought and treated unless they´re stimulated so that they become active,” Ananworanich said.


Human tissues and cells in parts like the central nervous system, eye cells and lymph nodes are some of the highlighted hosts of HIV reservoirs and so far there´s no existing therapy which can eliminate or treat HIV at that reservoir level.


Eradication/permanent cure versus functional cure

Even though the search for an HIV cure sounds more challenging than other HIV interventions currently, scientists are continuing to examine if a cure is possible.

Ndhlovu: Our focus now is the functional cure 
Scientist Zaza Ndhlovu says for now, the attention is on what is called a functional cure, not eradication.


“Functional cure is about eradicating as much of the virus as possible from the body and taming the virus reservoirs so that they don´t cause problems in the human body while eradication cure is about successfully cleaning the HIV reservoir and making the DNA completely free from HIV,” he argues.


According to Ndhlovu, a functional cure is realistic at least for now but scientists are quick to point out that a functional cure is as well a challenge to achieve with viral suppression as the best option for now.


Cure research/strategies underway

With lots of scientific debates going on how to define cure in the field of HIV and AIDS, different research strategies are underway. Most of the cure research results show that although the HIV reservoir cannot be dealt with, some cases of remission, up to 10 months, have been recorded. (Jantanat Ananworanich of the US Military research program defines remission as the maintenance of low or undetectable viral load in an HIV positive person for a reasonable period after discontinuation of therapy).


Scientists look at remission as a positive thing as the search for a functional cure continues however almost all cases of remission have rebounded.


Jessica Salzwedel Program Manager for AVAC, a global advocacy for HIV prevention organization, highlights that so far three functional cures are being investigated.


“A lot is being done out there. We have the Shock and Kill, Gene therapy/manipulation and immune modulation as active research strategies on cure underway” she said.


Cure research strategies explained:

Shock and kill strategy


Jessica Salzwedel explains that this strategy has two steps through which researchers aim at shocking the virus from the sleeping cells using drug intervention. The shock and kill strategy copies the cancer chemotherapy styles but researchers are trying to explore other procedures of performing it.

Gene therapy/Manipulation


Salzwedel highlights that genetic alteration of immune cells is what scientists focus on in this strategy.


“This will be carried out using three strategies, the first is to change the immune cell, the CD4 T cell, to protect them from HIV infection, then the immune cells will be enabled to find and fight HIV more effectively and the last step is removing HIV from the DNA of the infected cells,” she adds.


She was however quick to point out that this is a very complex procedure and challenging.

Immune modulation

According to Jessica Salzwedel, this strategy introduces drugs into an HIV infected person to cause some type of sustained change in the immune system to effectively fight the virus.


“Immune modulation will focus on identifying cells holding the virus before the cells reactivate and kill the virus before replication,” she explains.


Reference case stories in cure research

Although cure research has not lived up to what the world may have loved to be the general outcome (Eradication cure) so far there are just two cases of success reference in the history of research for HIV and AIDS cure.


The Mississippi baby

The Mississippi baby is one of the references that researchers refer to as a positive story of remission.


“Although we´ve had viral rebounds after having these cases on remission for about 10 months, the case of Mississippi baby is another positive thing to refer to on the possibilities of having a longer period of remission, however a lot of factors have to be checked in that case too” said Jintanat Ananworanich of the US Military research program.


The Mississippi baby was born to an HIV positive mother and was put on ART within 30 hours of birth. After several months of no therapy it was discovered that her viral load was undetectable however she had a viral rebound after 28 months of remission.

Timothy Brown “the Berlin patient”

The New England Journal of Medicine published that in 2006, apart from being HIV Positive Timothy was diagnosed with acute myeloid leukemia. His doctor arranged for a stem cell transplant. Timothy received two stem cell transplants from one donor in 2008 and 2007 and he stopped taking his antiretroviral medication on the day of his first transplant.


Three months after the first stem cell transplant, levels of HIV rapidly dropped to undetectable levels while his CD4 T cell count increased. In addition, blood and tissue samples from areas of the body where HIV is known to hide were tested and showed no existence of the virus.


Today, Timothy still remains off antiretroviral therapy and is considered cured.


The researchers and scientists are trying to imitate this procedure through gene therapy/manipulation strategy. However it has been argued to be the most time consuming, life threatening and expensive strategy.


For countries like Malawi, where HIV burden is still high and people are dying from AIDS related illnesses, any positive news on cure is a source of hope that one day the HIV epidemic will be history.

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