Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.

Reuters NewMedia - Wednesday June 2, 1999
Tony Munroe

The three were infected with a weakened form of HIV in Australia before May 1985 when universal screening for HIV blood was introduced in the country, said a report in Thursday's edition of the New England Journal of Medicine.

The three are part of a group of six infected with the weakened virus -- a blood donor and five surviving transfusion recipients.

They have lived AIDS-free from 14 to 18 years, which is longer than most HIV-positive groups, giving researchers hope that weakened strains of the virus could be used to develop vaccines against AIDS.

The new report on the six, known as the Sydney Blood Bank Cohort, showed that three members of the group were developing signs of immunological damage. The study, headed by Jennifer Learmont of the Australian Red Cross Blood Service-New South Wales, has followed the blood donor and transfusion recipients.

The cohort, first reported on in 1992, was infected with an attenuated, or weakened version of type 1 HIV (HIV-1), lacking a functional "Nef" genome and with a mutation in one of its regulatory sequences.

Two other members of the cohort died of non-HIV related causes, and one died of causes possibly related to HIV.

The authors concluded that the slow progress of HIV in the living cohort -- 14 to 18 years without symptoms -- was attributable to the specific mutation in their HIV.

Researchers suggested a drug inhibiting the actions of the Nef protein might prove effective in stemming the progression of HIV.

But the Sydney study corroborated other evidence showing that while the attenuation in the virus may slow its progress, immunodeficiency ultimately develops, posing challenges to its effectiveness as the basis for a vaccine.

"The problem facing researchers is that some low-level continuing replication of the virus is required to develop and sustain a protective immune response," Learmont's team wrote.

"Finding a balance between replication of the virus and protection is a critical issue if attenuated strains of HIV-1 are to be considered as the basis of a live attenuated vaccine," they wrote.

In an accompanying editorial Dr. Kathleen Collins of the University of Michigan and Dr. Gary Nabel of the National Institutes of Health wrote that the key remaining question was whether a further-attenuated version of HIV could be effective as a vaccine.

In a Reuters interview, Collins said the Sydney study "adds to the evidence that's out there already that attenuated viruses as vaccines are going to be more complicated than we had originally expected."
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