While long recognized as a prevalent infection among HIV+ persons, it is only within the last 2 years that mucosal herpes simplex virus (HSV) infections have become recognized as important factors in the transmission and clinical progression of HIV (1) . HIV virions are shed in genital lesions and in subclinical ulcerations (2) . The high frequency of HSV reactivation (>50% of days) and the multiple anatomic sites of reactivation in HIV+ persons influence HIV-1 RNA levels and subsequent disease progression (3-5) . Our initial studies of the immune response to HSV among HIV+ persons suggested that those with low frequencies of HSV-specific CD8+ T cell precursors (pCTL) as measured by limiting dilution analysis (LDA) had more severe HSV episodes than those who had high precursor frequencies (6) . In the initial funding period of this proposal, we proposed the hypothesis that this was likely due to inadequate CD4+ T cell help, and that like other opportunistic infections (OIs), increasing memory CD4 + T cell responses associated with HAART therapy would alter HSV reactivation rates. We were surprised to see that this was not the case; HAART therapy appears to have no discernible influence on HSV reactivation rates despite being associated with increases in HSV-specific CD4+ T cell responses. However, what has consistently emerged from both cross-sectional and longitudinal studies is the association between low numbers of pCTL and frequent HSV reactivation. This project is directed at the relationship between HSV - specific CD8+ T cell responses and mucosal reactivation rates of HSV.
