BBC News - August 20, 2006

HIV disarms the T cells sent by the body to fight it by flicking a molecular switch on the cells.

In the laboratory, the researchers were able to block this switch and restore T cell function, Nature reports.

Drugs are already available that can do the same, but the scientists say more safety studies are needed.

"Risky"

The drugs may not be specific enough and could cause nasty side-effects, they cautioned.

Lead researcher Bruce Walker, a Howard Hughes Medical Institute researcher at Massachusetts General Hospital in the US, said: "One has to proceed with real caution because if you turn back on an immune regulatory switch that the body has decided to turn off, you could trigger serious immunological problems."

Ideally, a treatment would only target the HIV-specific T cells, but techniques for such a targeted approach do not yet exist, he said.

The T cell switch controls a pathway of cellular events called programmed death-1 or PD-1.

The US researchers, working with colleagues at the Doris Duke Medical Research Institute in Durban, studied blood samples from 71 people who had recently contracted HIV but who had not yet commenced anti-HIV treatment.

They also looked at samples from four HIV-positive individuals taken before and after they had begun antiretroviral therapy.

HIV appeared to turn the T cell switch off, triggering the inhibitory PD-1 pathway.

"Turn off"

Furthermore, higher PD-1 expression was associated with more severe functional impairment of T cells.

PD-1 expression dropped when HIV treatment began, however. Blocking the PD-1 pathway restored T cell function.

He said the next step would be to see if the T cells can be turned back on in HIV-infected people in a way that will benefit them without incurring any serious side effects.

The researchers are also exploring whether PD-1 measurements could be used to guide treatment.

Dr Walker said: "Currently, we just count the number of T cells to decide when to treat someone, but we are excited about the possibility that adding PD-1 measurement might tell us more about the likelihood of progression of the disease and need for treatment in infected people."

Roger Pebody, treatment specialist for Terrence Higgins Trust, said: "This study is promising, and we hope that it will help researchers develop new therapies that may be available over the next decade."

A spokeswoman from the international HIV and Aids charity AVERT said: "This research is certainly encouraging, and fills another gap in scientists' knowledge about how HIV functions.

"However, as the researchers themselves say, further trials and studies are needed before we can hope to turn this knowledge into a new therapy for HIV, particularly if there is a risk of triggering any sort of auto-immune disease in the individual concerned."

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