July 11, 2001
Bruce Walker and his colleagues at Massachussetts General Hospital have added immensely to our understanding of how the immune system can control HIV. He gave another outstanding talk that both reviewed ongoing studies of acute seroconverters, and showed some fascinating new data on the importance of viral mutations that lead to escape from immune control.
By studying long-term non-progressors, Dr. Walker observed that maintaining HIV-specific CD4 help response is essential to maintain and effective cytotoxic T lymphocyte response (CTL). These CD4 help responses are lost early after primary infections.
Dr. Walker reviewed studies that he and Dr. Eric Rosenberg have been doing to study the effect of very early HAART in patients diagnosed during primary infection. As published earlier this year, when these patients underwent one or more treatment interruptions after more than a year of continuous suppression, a substantial proportion were able to control their viremia at very low levels. This control was associated with intact and broad CD4 help response and CTL responses.
In the second portion of the talk, Dr. Walker presented new information on the role of HLA-restricted immune responses and viral escape mutants. HLA B27 is associated with a good outcome in HIV infection, perhaps because B27 positive individuals target an important peptide epitope in gag. He reasoned that when a mother was B27-positive, her virus would have a chance to evolve into escape mutants. Since infants receive an allele for B27 from either the mother or the father, they reasoned that if the infant inherited B27 from the father, the virus would not have escaped from B27-directed CTL. Conversely, if they inherited the B27 allele from the mother, the virus they were infected with would have mutated to escape from this response. In fact, this is exactly what they found. Children who inherited B27 from the mother were rapid progressors; those who inherited B27 from the father were slow progressors.
This is one of the most striking demonstrations of the clinical impact of viral evolution to escape from immune control. The work needs to be confirmed across a variety of HLA loci and ethnic groups. Over time, the virus may evolve in specific regions to more effectively escape from immune control. However, the implications for vaccine development are potentially striking. Moreover, since HLA loci vary by ethnic group and region, it may effect the response of specific vaccines in different parts of the world.
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