Natural HIV immunity

An international, multi-institutional research consortium is seeking to discover how a few HIV-infected individuals are naturally able to suppress replication of the virus.

The Elite Controller Collaborative Study, the first large-scale haplotype-mapping study in people infected with HIV, is searching for genetic factors that may explain these individuals' unique ability to control the virus without treatment, sometimes as long as 25 years after infection.

"If we could discover how these individuals can coexist with this virus without damage to their immune system and could find a way to replicate that ability in others, we would have a recipe for halting the HIV epidemic," says Bruce Walker, MD, director of Partners AIDS Research Center (PARC) at Massachusetts General Hospital and an initial organizer of the Elite Controller Collaborative Study. Walker discussed the project in a media briefing today at the 16th International AIDS Conference in Toronto.

Most people infected with HIV cannot control replication of the virus with their immune systems alone. Unless antiviral medications are used, the virus continues to reproduce until it overwhelms the CD4 T helper cells, suppressing the immune response and leading to AIDS. In the early 1990s, it was recognized that a small minority of HIV-positive people remained healthy and did not progress to AIDS despite many years of infection. The term "long-term nonprogressors" was used to refer to this group. With today's more sensitive techniques for measuring viral levels in the bloodstream, individuals who are able to maintain low levels of HIV replication can be identified soon after their infection is diagnosed. Some of these viremic controllers can maintain viral loads below 2,000 copies/ml, while an even smaller group, called elite controllers, have viral loads too low to be detected by currently available assays.

"The primary goal of the Elite Controller Collaborative Study is to identify the mechanism that explains control of viral replication in both of these groups, " says Florencia Pereyra, MD, of PARC, lead coordinator of the research team. "We want to use that knowledge to develop a first-generation HIV vaccine, which may not cure or prevent infection but could successfully suppress viral levels. Since this natural ability is so rare, we need to work with collaborators around the world to recruit the number of participants we will need to determine what is going on.

"We expect to need data from at least 1,000 such individuals in order to define the genetic factors associated with this extraordinary outcome," she adds. "This effort will only be possible with the collaboration of HIV researchers, providers, advocacy groups and most important the HIV-infected individuals that fall in this category."

Those eligible to participate in the Elite Controller Collaborative Study are HIV-positive adults, aged 18 to 75, who have maintained viral loads below 2,000 copies without taking HIV antiviral medications. Participation involves having a single blood sample taken, which can be done by participants' local healthcare providers. Those located near a participating research center may choose to be followed over time and provide additional blood samples.