A quarter of a century since the virus that causes AIDS was identified, a vaccine against the deadly disease remains frustratingly out of reach despite a well-funded global effort to find a cure.
"Nearly a billion dollars is spent globally on HIV/AIDS research annually, and yet the sobering reality is that at present there are no promising candidates for an HIV vaccine," Bruce Walker of Harvard Medical School wrote in the May 9 edition of the journal Science.
The research community was dealt a heavy blow in September when the clinical trials of the most promising and widely tested HIV vaccine candidate were halted after it turned out to be a failure.
Early results showed that, rather than preventing HIV or reducing the viral load in people who received it, the experimental vaccine may have increased their chances of become infected.
"We share in the disappointment of the research and HIV communities today. Sadly, developing an effective AIDS vaccine remains one of the most challenging tasks facing modern medicine," Peter Kim, president of Merck Research Laboratories, which developed the candidate, said at the time.
Merck's vaccine aimed to stimulate T cells, a type of white blood cell key to the body's immune response, taking a different approach than numerous more traditional vaccines already tested without success.
"The (research) community is depressed because we see no hopeful route to success," American biologist and Nobel prize laureate David Baltimore said of the quest for an AIDS vaccine, at the opening of the latest conference of the American Association for the Advancement of Science, in February.
"Knowing how critical it is to get a vaccine for HIV, developers are moving ahead, even recognizing the long odds for success," he added.
The unique qualities of the HIV pathogen make developing a vaccine particularly challenging, Walker explained.
It has an enormous diversity of genetic sequences, and a great capacity to mutate and adapt, he said.
HIV strains can be divided into three different groups, of which the first, M, is itself divided into nine subtypes, with an undetermined number of variants.
One of the sub-type viruses can vary from 20 to 38 percent in Africa, where multiple variants exist.
Moreover, the retrovirus can undergo more mutations during the infection of a single individual than the entire world flu epidemic, which requires development of a new vaccine every year, Walker said.
With 33 million people living with HIV worldwide, developing a vaccine to protect simultaneously against all the pathogen's variants is a considerable challenge, Walker said.
And the fact that HIV is an infection of the immune system makes the task even more complicated, since traditional vaccines work by boosting the immune system to fight pathogens.
"There are so many things we do not know in this field of HIV vaccines," Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, said at a summit his organization hosted in March to evaluate the situation going forward following the failure of the Merck vaccine.
At the summit, leading AIDS specialists discussed avenues of research that remain largely unexplored, such as protection at the level of the mucous membranes, and the natural immunity of certain species of monkey to the primate equivalent of HIV, Simian immunodeficiency virus (SIV).