Paul Goepfert, MD, is an infectious diseases researcher largely focused on T cell immune responses in HIV infected patients. It is clear that CD8 T cells, and to perhaps a lesser extent CD4 T cells, are essential for control of HIV infection in infected individuals. Nevertheless, there are vast differences in the quality of HIV-specific T cells with patients exhibiting varying degrees of viral control.

We were among the first group to demonstrate that HIV-specific CD8 T cells were relatively dysfunctional in patients with progressive disease and among the first to demonstrate that CD8 T cell targeting conserved HIV proteins was associated with a better prognosis. We have determined that HIV has a more difficult time mutating at conserved regions. While the association between viral adaptation and lack of viral control is well established, we recently definitively demonstrated that viral adaptation to CD8 T cells actually predicted loss of viral control.

In fact, individuals infected with HIV more pre-adapted to their CD8 T cells fair worse in terms of set point viral load and CD4 T cell decline. Furthermore, in situations where the virus is able to mutate at conserved sites, the resultant mutation in many cases results in a virus that is less able to replicate in vivo. Our laboratory has also recently demonstrated the importance of CD4 T cell responses in shaping the evolutionary changes seen HIV infection. In total our findings have led into further insight for therapeutic and preventative HIV vaccine development.

Dr. Goepfert has also amassed a great deal of clinical trial experience especially relating to the clinical testing of preventative HIV vaccines and have done so for almost 20 years. During this time, we have assisted in the enrollment of over 50 phase I, 5 phase II, and 4 HIV vaccine efficacy studies.


Human leukocyte antigen class I (HLA)-restricted CD8+ T lymphocyte (CTL) responses are crucial to HIV-1 control. Although HIV can evade these responses, the longer-term impact of viral escape mutants remains unclear, as these variants can also reduce intrinsic viral fitness. To address this, we here developed a metric to determine the degree of HIV adaptation to an HLA profile. We demonstrate that transmission of viruses that are pre-adapted to the HLA molecules expressed in the recipient is associated with impaired immunogenicity, elevated viral load and accelerated CD4+ T cell decline.

Furthermore, the extent of pre-adaptation among circulating viruses explains much of the variation in outcomes attributed to the expression of certain HLA alleles. Thus, viral pre-adaptation exploits 'holes' in the immune response. Accounting for these holes may be key for vaccine strategies seeking to elicit functional responses from viral variants, and to HIV cure strategies that require broad CTL responses to achieve successful eradication of HIV reservoirs.

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