HIV/AIDS: 30 years of success and setbacks
AIDS: 30 years on Big names in medicine are set to give an upbeat assessment of the war on AIDS this week, 30 years after French researchers identified the virus that causes the disease.
But meanwhile, researchers are scratching their head over the failure of recent vaccine trials.
At a conference in Paris, scientists will pay tribute to the astonishing success of AIDS drugs and highlight steps being taken towards a cure - a goal once deemed all but out of reach.
The three-day 30 years of HIV science: Imagine the future conference builds on the 30th anniversary on Monday of the Nobel-winning isolation of the human immunodeficiency virus (HIV) by Dr Luc Montagnier of France's Pasteur Institute, and colleagues.
"The discovery of HIV in 1983 and the proof that it was the cause of AIDS in 1984 were the first major scientific breakthroughs that provided a specific target for blood-screening tests and opened the doorway to the development of antiretroviral medications," says Dr Anthony Fauci, director of the US National Institute of Allergy and Infectious Diseases.
Introduced in 1996, after many years of frantic drug research, antiretrovirals are saving the lives of millions of people infected with HIV and helping to contain the virus' spread, says Fauci.
By suppressing viral levels, antiretrovirals can prevent HIV being transmitted by pregnant women to their unborn children, and by infected people to their sexual partners.
'Gap' for HIV vaccine efforts after latest setback
But there have also been setbacks, particularly in the quest for a vaccine.
The hunt for an HIV vaccine has gobbled up $8 billion in the past decade, and the failure of the most recent efficacy trial has delivered yet another setback to 26 years of efforts.
With the next attempts expected to be years away, top researchers now say there is a "void" or a "gap" in current clinical trial efforts to test whether a vaccine may be safe and effective in people.
A kind of ongoing autopsy of the last four major bids to make an HIV vaccine has informed the field as to what does not work, with the latest casualty being a trial called HVTN 505 that was halted early because it did not prevent HIV.
"It leaves us with a gap in several years before we have another HIV vaccine efficacy trial under way, and that is unfortunate," says Dr James Kublin, executive director of the HIV Vaccine Trials Network.
Another concern for researchers is that two vaccine trials - HVTN 505 and a previous trial known as STEP that ended unsuccessfully in 2007 - both revealed apparent increases in the number of vaccinated patients who got HIV.
HVTN 505 showed 41 cases of HIV were acquired in the vaccine group, compared to 31 in the placebo group. Among some 2,500 participants, the difference was not statistically significant, and so researchers found that no harm was caused by the trial.
"But the number is in the wrong direction," says trial leader Dr Scott Hammer of Columbia University, who described the trial's outcome as a "disappointment".
The key puzzle in the vaccine search has been the nature of the human immunodeficiency virus itself, which has managed to fool modern medicine by changing its genetic makeup so often that a single weapon cannot silence it.
"It is more variable than almost any other virus that a vaccine has been attempted for. So if one wants to make antibodies against a virus that is variable, one has to have a broadly reactive antibody," says Dr Wayne Koff, chief scientific officer at the International AIDS Vaccine Initiative (IAVI).
A small number of HIV-positive people have been found to produce antibodies that can neutralise a broad range of HIV variants, but scientists have not yet figured out how to make a vaccine from that information.
The sole success story to date has been a trial in Thailand known as RV144, which in 2009 saw a modest, 31 percent rate of protection, still far below the 50 percent threshold needed in order to license a vaccine.
Researchers are continuing to study the results for clues as to why it worked in some cases but not others, and why it appears the protective effects may have waned over time.
A similar vaccine modelled for South Africans is expected to enter human trials in the next couple of years. Other approaches for increasing T cell immunity are also on the horizon.
Cure is the main hope
Counter-intuitively, the main hope nowadays seems to rest on a cure.
Three years ago, Dr Francoise Barre-Sinoussi - a 2008 Nobel co-recipient with Montagnier - mapped a strategy for attacking HIV's 'reservoir.'
This is the cellular bolthole where the virus lurks after being pounded with antiretrovirals. Once the drugs are stopped, the virus re-emerges and spreads once more through the bloodstream.
"The great challenge will be to fully understand where the virus hides, how it manages to stay hidden so effectively and how to lure it out of its hiding place. We've learnt a lot about this in the past few years," says Australian researcher, Dr Sharon Lewin, a professor at Monash University in Melbourne.
Lewin is part of a team cautiously experimenting with an anti-cancer drug to flush out the virus that destroys the immune system and exposes infected people to pneumonia, TB, and other opportunistic diseases.
In trials on 20 patients, the cancer drug awoke the dormant virus in 90 per cent of volunteers. The ultimate goal is to kill the newly-exposed virus, leaving the cell it hid in to die eventually of old age.
"We do have drugs that seem to wake up the virus but these are only the first steps in ultimately clearing it out completely," says Lewin.
About 34 million people are infected with HIV worldwide, and AIDS has killed 30 million people since the epidemic began 30 years ago.