adminRoselyne Sachiti recently in Melbourne, Australia
A follower of one of the many Pentecostal churches in Zimbabwe hops and runs as he makes his way to the podium. It is a cool Sunday afternoon in March 2014 and he stands in front of over 30 000 other followers to announce that he has been cured of HIV and has his latest results to
prove it.
The man has been living with the disease for 11 years and attributes his cure to the powerful prayers from his pastor.
He has stopped taking antiretroviral drugs. But, a year later, the disease resurfaces. His faith was too weak, some people from his church tell him.
Not long afterwards, he dies.
Thousands of kilometres away, news that a baby from the United States, known as the Mississippi child, thought to be cured of HIV, had rebounded with detectable levels of the virus in her blood breaks.
The child was born to a mother who received no prenatal care and was not diagnosed as HIV positive herself until just before delivery. As such she missed out on the prevention of mother to child transmission intervention, which has saved lives of many babies the world over. In a frantic move to control the virus, doctors administered high doses of three antiretroviral drugs 30 hours after the girl was born, in case she was infected. At that time, the virus was not detectable but they had to protect the girl who remained on ARVs for about 18 months. For unknown reasons, her mother stopped taking her medication.
A few months later, doctors said there was no evidence of the little girl having HIV in her blood. The good news broke, the girl was the first child to be functionally cured of HIV.
A functional cure is when the presence of the virus is so small lifelong treatment is not necessary and standard clinical tests cannot detect the virus in the blood.
But at the beginning of July this year, bad news trickled in. Researchers explained the Mississippi infant remained virus free for 27 months as the cure was downgraded to remission. Thus, the issue of remission and fishing out HIV from the reservoir it hibernates in became one of the most talked about topics at the just ended 20th International Aids Conference in Melbourne, Australia. A top AIDS 2014 official and scientist Professor Sharon Lewin explained how latest research proved that HIV could hide in one single cell, making someone appear negative as in the Mississippi baby case.
She revealed how scientists also realised last year that the HIV virus can hang around for a long time and pop up at an unexpected time.
“This is what we found in the Mississippi baby. What we have learnt from that is we need better tools to measure virus while people are on treatment and once they stop. We need much better assays to know where that virus is hiding.
“The most recent cases of the Mississipi baby and the Boston patient who also rebounded after stopping treatment tell us that we should not only tackle the virus that persists on treatment but also need a good immune response ready to tackle any virus that emerges,” she added.
Prof Lewin added that their efforts for an HIV cure were currently on developing treatments leading to remission.
“Latest research and findings are significant in that they have shown us that we can wake up the virus reservoir and make enough of the virus to leave the cell, making it visible to an immune response.
“Although we know early treatment most likely significantly reduces the amount of virus that persists in patients on ART, most people get treated during the chronic establishment and we still need to understand how to eliminate those long lived reservoirs of the virus.
“At the moment we have talked largely about kick and kill strategies but we probably need to develop other approaches to those long lived reservoirs,” she said.
A researcher and professor of medicine at the University of California, San Francisco, Dr Steven Deeks said for scientists, failures were more important than successes. He described the Mississippi baby as a great success, scientifically.
“Scientifically, there are three big issues that should be tackled. We need to know which cell the virus is and where it resides.
“We should measure the virus better. There are dozens of cases in the world where people have no detectable virus and are on therapy and may claim to be cured. We need better ways to measure this.
“We should translate some of the early pilot studies into real clinical studies to see if we can actually advance the cure agenda,” he explained.
Dr Deeks also said it was clear that the international community was fully engaged in research.
“Funders are engaged, foundations, communities, most academic groups. There is a tremendous amount of interest. In future in terms of potential barriers to success, one major group not fully engaged is industry. We are not going to cure anyone unless we develop any drugs and that’s what industry does.
“There is a lot of effort in trying to identify the barriers that are preventing industry from getting engaged and I think we know what they are and how to overcome them.”
Researchers also revealed that an anti-cancer drug, romidepsin, could reactivate hidden HIV in patients to make it detectable in what they call the kick and kill approach. Researchers like Ole Schmeltz Sogaard said the kick and kill approach was a step in the right direction as it would fish out HIV from the cell in which it was archiving.
“There is still a long way to go and many obstacles to overcome before we can start talking about a cure for HIV,” Sogaard said.
Speaking to journalists, Sogaard, who led the research from Aarhus University Hospital in Denmark, said their team gave three once weekly infusions of anti-cancer drugs, romidepsin, to six HIV positive adult patients of five males and one female who were already taking antiretroviral drugs and whose “viral load” was undetectable over nine and a half years. Their findings indicated that romidepsin increased the virus production in HIV infected cells; between 2.1 and 3.9 times above normal and the viral load in the blood increased to measurable levels in one out of six patients.
“We infused romidepsin three times over a period of 40 days and what we saw was a significant release of viral particles from latently infected cells into the bloodstream of these six patients despite them being on treatment. These viral particles were easily detectable with standard clinical analysis.
“We wanted to find out if we could see a significant reduction in the size of the reservoir of these patients. But from our preliminary findings, it does not look like there is a significant reduction in the size of the reservoir. What this tells us is that we can activate cells and induce the release of viral particles into the blood of the patients but this is not enough to make a difference on the size of the reservoir,” he said.
He also explained how the virus was activated and moved toward the bloodstream, leaving a trace on the outside of the infected CD4 cells. In principle, this means killer T-cells would be able to trace and destroy the HIV-infected CD4 cells.
“These results are being seen as a promising step to show that latent HIV can be activated but just not sufficiently to cause the death of latently infected cells and reduce the reservoir,” he said.
Sogaard added that the next step was a larger trial where the Danish researchers would combine romidepsin activation of hidden HIV with an experimental vaccine called Vacc-4x being developed by the Norwegian biotech firm Bionor Pharma to strengthen the ability of T-cells to fight HIV.
An assistant member and a principal investigator at the Vaccine & Gene Therapy Institute of Florida, Dr Nicholas Chomont, said it was the scientific priority of the International Aids Society to develop novellas to measure the size of the reservoir.
“It is important because we want to find ways to measure the efficacy of eradication strategies. The ones we currently have are expensive and require a lot of blood and not exactly sure what they measure. We spent a lot of time during the past few years trying to find novellas that can be used in dose eradication trials. We came up with TILDA, which requires 10mml of blood and can be run in two days and can be implemented in any lab in the world,” he said.
In an overview lecture on cure and vaccine research, Dr Anthony Fauci, head of the US National Institute of Allergy and Infectious Diseases (NIAID) since 1984, highlighted the Mississippi baby as an optimistic case of prolonged virological remission that was just not sustained.
“Given the lack of antibody response, we need to know what maintained that suppression for so long and what triggered the rebound. For a future cure to be effective in a global context, he noted that it “needs to be simple, safe and generally applicable”.
He remains hopeful for a vaccine, following recent discovery of broadly neutralising antibodies and new research into B-cell lineage vaccine design.
The researchers also called for the engagement of low income countries in the search for an HIV cure as 80 percent of people living with the virus are from such nations. Prof Lewin said: “There is need for more engagement with the pharmaceutical industry through the creation of public-private-partnerships. Some companies have already been actively involved in this area and this should be extended in their efforts to towards developing a public-private partnership.”
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