The scientists discovered that HIV disarms the T cells sent by the body to fight it by activating a molecular switch on the cells.
The discovery is a positive step in producing more targeted drug therapies. While drugs are already available, which can block this switch and restore T cell function the danger of reversing an immune regulatory switch that the body has turned off could trigger serious immunological problems.
Researchers commented that the drugs may not be specific enough and could cause nasty side effects.
In the study, the researchers from the US, working in conjunction with colleagues at the Doris Duke Medical Research Institute in Durban, studied blood samples from 71 HIV-positive people who had not started an anti-HIV treatment.
Their research 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 a molecular pathway involving a receptor called PD-1 (Programmed Death-1). The pathway inhibits the immune system in chronic viral infections - those in which the immune system does not completely clear the virus.
"It has been thought that the ineffectiveness of HIV-specific T cells resulted from progressive, irreversible damage or bad cellular 'programming'," said Daniel Kaufmann, of PARC and the MGH Infectious Disease Unit, a co-first author of the paper.
"While this might still be partially the case, our finding that defects in important functions of exhausted T cells can be reversed demonstrates that active inhibitory mechanisms may play a major role in blocking T cell function. In other words, the cells may be turned off but not permanently disabled."
Higher PD-1 expression has been associated with more severe functional impairment of T cells. The researchers found that PD-1 expression dropped when HIV treatment began. Blocking the PD-1 pathway restored T cell function.
The researchers said the next step would be to see if the T cells could be turned back on in HIV-infected people in a way that will benefit them without incurring any serious side effects.
Additionally, the avenue of exploring PD-1 measurements and whether they could be used to guide treatment is also a possibility.
"Natural regulatory systems that help control the immune system appear to be shutting it down before its work is done," said co-first author Cheryl Day.
"One of the next questions we need to answer is whether we can turn it back on for HIV-infected patients in a way that will benefit them without incurring serious side effects."
The study appears in an early online publication of Nature.