PARIS: Variations in two key genes help determine how swiftly an individual infected with HIV progresses to AIDS, according to a study published on Sunday in the journal Nature Immunology.

The finding challenges quarter-century-old wisdom that what chiefly drives the advance to AIDS is "viral load," the amount of HIV in the blood, whose relentless rise bludgeons the immune system, the researchers say.

Instead, they argue, the situation is more complex. An individual's genetic profile can greatly affect replication of the human immunodeficiency virus (HIV) as well as the body's response to the intruder.

The interaction between the virus and the immune system switches "an otherwise benign infection to a lethal one," they say. The genes in question are called CCR5 and CCL3L1, although other genes, still not fully explored, may also play a part.

CCR5 controls a key receptor, or docking point, on the surface of the CD4 immune cell onto which HIV latches. CCL3L1, meanwhile, controls an immune system signalling molecule called a chemokine that prevents the virus attaching itself to the CCR5 receptor.

Previous work has already established that certain genetic variants in CCR5 appear to give a shield against viral entry.

In 2005, the same team that reports on Sunday, led by Sunil Ahuja of the University of Texas Health Science Center in San Antonio, found that the number of copies of the CCL3L1 genes is also a factor.

People with extra copies of this gene - the number of copies varies according to the individual from zero to five and more - are less likely to become infected by HIV.

In the latest work, Ahuja's team determined several genetic "risk groups," based on the combination of favourable or unfavourable CCR5 mutations and the number of CCL3L1 copies.

They then analysed a cohort of 3,500 HIV-infected US patients and healthy individuals to see at what stage those with the virus advanced to full-blown disease, and compared this to their "risk group" profile and immune response.

The viral load at the early stages of infection accounted for only 9% of the difference in speed at which HIV-infected people progressed to AIDS.

Just as important was the sort of combination of the two genes. "The genetic variations contribute nearly as much to the extent of inter-individual variability in AIDS progression rates as does HIV-1 viral load," Ahuja said.

"Even after accounting for the detrimental effects of a high viral burden, these genetic factors influence the pace of HIV-1 disease progression," said Hemant Kulkarni, co-first author of the paper and assistant professor of medicine at the Health Science Center.

The CCR5-CCL3L1 profile also has an effect on the immune responses among healthy people, which suggest that this combination might play a role in how the body responds to other infectious diseases, the paper suggests.

The other co-first author, Matthew Dolan, from America's San Antonio Military Medical Center, said the finding could have some major implications.

It strengthens the goal, still distant, of tailoring HIV drugs and vaccines to an individual's genetic ID, Dolan said.

Similar research in the field of genetic variation and HIV has looked at differences among three genes that control signalling molecules called human leucocyte antigens (HLA), which tag an intruder for destruction by the immune system.

A total of 39.5 million people were living with HIV or AIDS at the end of 2006, according to figures released last December by UNAIDS and the World Health Organisation (WHO). And this dreaded figure is constantly rising.