"It isn't that we're going to completely stop and turn around 180 degrees, but we're going to torque or turn the knob on the system much more toward asking and answering some of the fundamental questions that we have not been able to answer up to now," Fauci says.

Worldwide, an estimated 33.2 million people are living with HIV/AIDS, and at least 25 million people have died from the disease, which is transmitted through sex or infected blood.

The disease, which erodes the body's immunity against infections, is fatal for those who don't take life-prolonging drugs. Its social and economic impact is especially profound because it strikes young adults in their prime earning and parenting years. The disease has carved huge holes in communities across large parts of Africa and Asia.

Improvements in drug therapy have extended life expectancy and in the absence of a vaccine, the current fight against HIV/AIDS focuses on increasing access to affordable drugs, and raising awareness of preventive measures like the use of condoms.

The biennial international AIDS conference will be held next month in Mexico City. Fauci, who will attend, stresses the need to "bring expectations down to realistic levels".

"We have to understand how difficult the situation is, and not expect that ... tomorrow we're going to start a large vaccine trial and we're going to get the answer in a couple of years," he says. "It is extremely unlikely that that will happen."

The traditional approach to creating vaccines - using the live virus to induce antibodies, and thus stimulating natural immunity in patients without causing the illness - has not worked with HIV. This is because the virus has an astonishing ability to change and disguise itself from the body's defenses.

Instead, the research focus in recent years has been on alternative approaches, in order to at least get something onto the market.

The PAVE and Merck vaccines represented an attempt to create a cellular immunity response, in other words to program the body's T-cells to search out and destroy virus-infected cells.

The goal was to reduce the HIV virus count in the body, slow down the progression of the disease and reduce the possibility of transmission from an infected person, even without completely eliminating the presence of the virus.

Hope for this approach rose two years ago, as the PAVE and Merck vaccines headed toward advanced trials in humans. However, trial results were disappointing.

Like the dead end with the Vaxgen vaccine in Thailand in 2003, the failure dashed soaring expectations.

Fauci says that his main goal has not changed since he began in the field of HIV research in the 1980s. He wants to crack the code and "identify that part of the virus that actually is capable of inducing a (broadly) neutralizing antibody".

Ten percent of the world population appears to have a natural immunity but scientists haven't figured out how it works.

Among the keys to the mystery are what scientists call the "correlates of immunity".

In normal virus infections, this refers to the antibodies that can be tested for and would indicate immunity to, say, influenza, rubella, polio or measles.

But with HIV, the presence of antibodies does not protect against the disease. Scientists are still searching for a correlate that will neutralize a range of HIV strains.

As part of current efforts, Fauci's institute will spend more money on basic HIV research in the hopes of luring younger scientists who think "outside the box" and are willing to pursue "innovative, high risk, high impact" work, according to the NIAID documents about the new programs.

"We'd like to bring into the fold and embrace new people, young investigators ... who have no preconceived notions," Fauci says.

(China Daily July 31,2008)