Francoise Barre-Sinoussi, Nobel Prize laureate and co-discoverer of HIV in 1983, said that in her opinion a cure for HIV “is almost an impossible mission,” but a “functional cure” and vaccine might be achievable.
In this article, KaleidoScot explores the issues at stake and outlines her substantive arguments in light of what is known so far.
Barre-Sinoussi made her statement, which has disappointed many, in response to questions posted by the public in an interview with CNN at the International AIDS Society Conference, in Vancouver.
The pioneering scientist who has been a leading edge researcher and long time vocal advocate of HIV treatment and rights, made this commentary in relation to recent various studies that claimed a cure may be possible.
“A cure for me is almost an impossible mission because the reservoir of cells is not only in the blood. How to eliminate all the cells which are reservoirs is why I say it’s an impossible mission. They are everywhere — in the gut, in the brain, in all the lymphoid tissue”, said Barre-Sinoussi.
“Even if you have a very efficient strategy, how you can make sure that there’s not one or two cells still there and if one is there the virus will reappear again? That’s why I say it’s an impossible mission.”
“But you never know”, she added.
Total cure unlikely
Her comments are consistent with last year’s findings regarding the “Boston patients” — two men who received bone marrow transplants to treat their blood cancer called lymphoma appeared to rid them completely of the HIV virus — had relapsed and gone back onto antiretroviral treatment. It seems the HIV virus was not eradicated completely and after a period where it was totally undetectable it appears the virus managed to hide and then replicate itself.
Further supporting this finding is a recent UK study, published late last week in EBioMedicine, which showed that HIV can continue to multiply in patients who are responding well to antiretroviral therapy.
“This research shows that sadly, the HIV virus has found yet another way to escape our treatments,” said study leader Anna Maria Geretti, a professor from the University of Liverpool in the United Kingdom, said in a university news release.
During treatment, the virus can avoid elimination by hiding in blood cells that trigger an immune response. HIV does this by integrating its own genetic information into the DNA of immune system cells called CD4 cells, explained investigators.
Researchers checked levels of integrated HIV in the CD4 cells of patients who had been receiving antiretroviral therapy for between one to 14 years, finding the levels were substantially the same in all of the patients.
Results indicate that whenever an HIV-tainted CD4 cell copies itself to produce more cells, it also copies the HIV genes. “We always knew HIV is difficult to suppress completely and that it hides inside CD4 cells, but we always hoped that as the body gradually renews its CD4 cells that the hidden HIV would die out. We were surprised to find that the levels of HIV integrated in the CD4 cells didn’t reduce over the 14-year period,” Geretti said.
“The good news is that we did not see any worsening over time, but the bad news is that these findings really cast doubt over whether HIV can be ‘cured’ by increasing immune cell responses against it — a strategy that now looks like it will eventually fail,” Geretti concluded.
Sharon Lewin, an HIV expert at Monash University in Australia, explaining such developments said: “We’ve learnt many things here – and one of the most important is that a tiny, tiny amount of virus can get the whole thing going again”.
In other words, this confirms the scepticism of Barre-Sinoussi regarding the possibility of a preferable solution to be able to eradicate HIV from the body of an infected person and cure the infection once and for all.
Functional cure is possible
Barre-Sinoussi, however, is more optimistic about a “functional cure” although she prefers the term “remission (when the virus is brought down to low levels in the body) … That’s possible”, she said. “I’m convinced one day — I don’t know when — we will have a strategy to induce durable remission.
Two “Berlin patients”, one remaining anonymous, the other being Timothy Ray Brown, an HIV positive American living in Berlin, were “functionally cured” as part of a treatment to acute myeloid leukaemia.
Brown received a stem cell transplant from a donor naturally resistant to HIV and has remained off antiretroviral therapy since the first day of his stem cell transplant. Their stories were chronicled in the 2014 book, Cured: The People who Defeated HIV. The study along with a second Emory University PLOS study on rhesus monkeys shows that the stem cell donation is probably responsible for the functional cure, while radiation therapy destroyed many of the infected cells. It is possible, but not proven, that Brown’s donor mutation simply left his immune system insulated against HIV, therefore probably providing the “functional cure”.
A small group of individuals have been “functionally cured” or “in remission” because they still harbour the virus within their bodies but it remains largely undetectable and they do not need to take antiretroviral therapy.
These include Brown and the Visconti cohort, a group of fourteen patients receiving early therapy for the virus. A child known as the Mississippi baby was once considered part of this small group but has since suffered a relapse.
Researchers are therefore hopeful regarding a two-pronged approach which aims to firmly suppress the virus while bolstering the immune system, this is probably the best way forward and may, in the near future, provide a “functional cure.”
“We need to attack in two ways – reduce the virus to very low levels and also to boost the immune response. We can’t do one without the other,” said Lewin.
“So we still have to think of other creative ways to control HIV. And it’s still early days… before we can say which approach is likely to be the winner.”
Vaccine is a possibility
With regards to a vaccine Barre-Sinoussi remains relatively helpful, “in the last six – seven years we are starting to see a lot of progress in the field of HIV vaccine.
“I think the field of vaccinology in general is moving and maybe I am too optimistic, but I like to think because of HIV the field of vaccinology globally is moving, not only for HIV.”
An initial pivotal research shows a promising new antibody treatment that reduces 300-fold HIV in positive people’s blood systems could potentially be developed into a vaccine.
The newly created antibody, named 3BNC117, by a team of top US and German scientists suppressed HIV in the blood without any harmful side effects for up to a month.
The lead author, Michel Nussenzweig, said that the “goal is a once-a-year shot for prevention and a combination approach for [functional] cure.” The antibody could also potentially offer an alternative treatment to the anti-retroviral drugs currently used.
In short there are encouraging studies that show HIV positive people may be able in the near future to undergo long-term remission without requiring lifelong therapies – “functional cure”, but total eradication of the virus from the body is unlikely (i.e. full cure).
Although so far researchers have been unsuccessful to come up with a vaccine, recent studies show that it may be possibility within the near future.
These studies along with new prevention approaches which could include PrEP may prove very effective in lowering infection rates and improving HIV positive people’s lives.
Other issues that Barre-Sinoussi is concerned about are prejudice and stigma that has still lingered on from the 80s, namely that the gay population and the intravenous (IV) drug users are the main suffers/carriers of HIV/AIDS.
The assumption is “it’s a disease that particularly affects those people that are vulnerable but that do not belong to the regular population…”
She adds “…not everybody is accepting of those populations. That makes me really mad. Really mad.”