By Michael Smith, North American Correspondent, MedPage Today
Published: May 20, 2013
There was no fanfare on May 20, 1983 when Science published what is undoubtedly among the most important medical papers of the 20th century.
In the usual dry prose, researchers from the Institut Pasteur in Paris described a new retrovirus, which they dubbed lymphoadenopathy associated virus, or LAV.
It was, they reported, a "typical type-C RNA tumor virus" with a tropism for T-lymphocytes and was similar to -- but clearly distinct from -- human T-cell leukemia viruses, which had recently been discovered.
Today, we know it simply as HIV.
That paper made very little immediate impression, according to Françoise Barré-Sinoussi, PhD, of the Pasteur institute, who was the lead author and who later shared the 2008 Nobel prize in medicine for the discovery with the senior author Luc Montagnier, PhD.
Partly that was because HIV/AIDS -- although mysterious and deadly -- was not yet seen as a global threat.
Finding the virus "was not just an academic problem," Barré-Sinoussi told MedPage Today. "But there were only a few cases and we did not yet have the idea of the magnitude of the infection, the magnitude of the epidemic."
And the scientific community wanted more before breaking out the champagne. "We had to accumulate more data about the links between the virus itself and the disease," she said.
For those studying the issue, "it was a very important paper," commented Anthony Fauci, MD, director of the National Institute for Allergy and Infectious Diseases.
But it wasn't a "slam-dunk," he told MedPage Today. "Although it was clear they had isolated the virus ... there was no way to definitively diagnose people who were presenting at hospitals" so there was a missing link.
It was still necessary to demonstrate epidemiological links between the virus and people with AIDS, a demonstration that came the next year with papers by Robert Gallo, MD, then at the National Cancer Institute, and colleagues, Fauci said.
That research provided "epidemiological and serological proof that the virus was unequivocally associated with the disease that we were just then starting to call AIDS," he said.
But as that data accumulated, it became evident that French discovery was indeed significant -- the cause of the disease was finally known. Researchers optimistically talked about vaccines and cures as if they would be -- not easy, perhaps -- but not out of reach.
This week in Paris, the Pasteur institute will play host to an international symposium to mark the 30th anniversary of that discovery and there is a renewed sense of optimism about the pandemic.
But there is also an understanding that HIV remains a tough challenge, Fauci said. He is to deliver a keynote talk and part of its title sums up the past three decades of HIV/AIDS research: "much accomplished, much to do."
Among the "much to do," Fauci said, is to crack the tough problems of a vaccine and a cure -- the same tough problems that have dogged the field since 1983.
At that time, he said, "we didn't realize that HIV was such a difficult virus" and it wasn't yet clear that it would not easily surrender to medical science.
On the vaccine front, for instance, the usual approach is to try to mimic nature -- cause an immune response that first halts, then clears, and then protects against the disease.
But in HIV, that's not nature's way, Fauci noted. With vanishingly few exceptions, no one mounts an immune response that stops, clears, and protects against HIV.
"If you're going to develop a vaccine you're going to have to do better than nature," he said.
So far, of course, researchers have not managed to do that.
Along with the 20,000-foot view that Fauci brings to the table, the Paris symposium will hear more about the basic science of HIV and its interaction with the immune system, which 30 years later, is still not completely understood, according to Barré-Sinoussi.
"We need to have some new discoveries in the field of immunology," she said. "There are still some missing pieces of the puzzle."
Barré-Sinoussi said she's also expecting to hear more about the so-called "functional cures" that made headlines earlier this year. In a functional cure, patients still remain infected, but they can control the virus without the aid of antiretroviral medications.
Exactly how that can be made to happen reliably remains an open question that -- if it could be answered -- would change the face of the HIV/AIDS pandemic.
She's looking forward to reports on the mechanisms by which HIV establishes itself in the body and then persists despite antiretroviral medications that prevent it from replicating.
And there will be more details at the symposium about vaccine research, including a debate on the best way to move forward after the partial success of a major trial 4 years ago and the recent failure of another.
What Barré-Sinoussi is not expecting is anything dramatic. An announcement of a breakthrough "would be wonderful, but I don't think we will have that."
On the other hand, no one immediately recognized the breakthrough by her and her colleagues 30 years ago, so time may tell.
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