Billions of dollars later and still no Aids 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 is only the latest setback to 26 years of effort.
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 is safe and effective.
An autopsy on the past four big bids to make an HIV vaccine has informed the field as to what does not work, the latest casualty being a trial of HVTN 505 that was halted early because it did not prevent HIV.
"It leaves us with a gap of several years before we [can expect to] have another HIV vaccine-efficacy trial under way and that is unfortunate," said 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, that of STEP, ended unsuccessfully in 2007 - both revealed what appeared to be increases in the number of vaccinated patients who got HIV.
With HVTN 505, 41 cases of HIV were recorded in the vaccinated group, compared to 31 in the placebo group. Among some 2500 participants, the difference was not statistically significant, so researchers found no harm was caused by the trial.
"But the number is in the wrong direction," said trial leader Scott Hammer, who described the trial's outcome as "a disappointment". Researchers are still investigating why this happened but some suggest that the common-cold virus, Ad5, which was used as a vector for delivering the vaccine, might have caused more HIV infections by making it easier for the virus to enter the body.
Hammer, a professor of medicine at Columbia University, said that the use of Ad5 might now be considered too risky and other options are being investigated.
The key puzzle in the vaccine search has been the nature of the HIV (human immunodeficiency virus), which has managed to fool modern medicine by changing its genetic make-up so often that a single weapon cannot silence it.
"The virus is a very elusive foe," said Wayne Koff, chief scientific officer at the International Aids Vaccine Initiative.
"It is more variable than almost any other virus for which a vaccine has been attempted," he said.
A small number of HIV-positive people have produced 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.
About 34million people are infected with HIV worldwide and Aids has killed 30million people since it surfaced 30 years ago.
The sole success story to date has been a trial in Thailand of RV144, which in 2009 produced a modest, 31% rate of protection, still far below the 50% threshold needed to license a vaccine.
Researchers continue to study test results for clues as to why it worked in some cases but not others, and why it appears the protective effects have waned over time.
A similar vaccine modelled for South Africans is expected to enter human trials in the next few years.
"I am an optimist. I think we are at least halfway there - I hope further," said Hammer. "The world needs a vaccine."