Severe genital herpes infections in HIV-infected individuals with impaired herpes simplex virus-specific CD8+ cytotoxic T lymphocyte responses

The specific mechanisms underlying the varied susceptibility of HIV-infected (HIV+) individuals to opportunistic infections (OI) are still incompletely understood, One hypothesis is that quantitative differences in specific T cell responses to a colonizing organism determine the development of an AIDS-defining OI, We evaluated this hypothesis for herpes simplex virus (HSV) infection, a common OI in HIVS patients, Using limiting dilution analyses, the frequency of HSV-specific CD8(+) cytotoxic T lymphocyte precursors (pCTL) and proliferative precursors were quantitated in peripheral blood mononuclear cells from 20 patients coinfected with HIV and HSV-2. The frequency of HSV-specific CD8(+) pCTL in HSV+HIV+ individuals was significantly lower than in HSV+HIV- individuals (1 in 77,000 vs, 1 in 6,000, P = .0005) and was not different than in HSV-HIV- individuals (1 in 100,000, P = .24), HIV+ patients who suffered more severe genital herpes recurrences had significantly lower HSV-specific CD8(+) pCTL frequencies than those patients with mild recurrences (1 in 170,000 vs, 1 in 26,000, P = .03), In contrast, no significant difference was seen in proliferative precursor frequencies between those patients with mild vs, severe genital herpes (1 in 3,800 vs, 1 in 6,600, P > .5). Quantitative differences in pCTL frequency to HSV appear to be the most important host factor influencing the frequency and severity of HSV reactivation in HIV+ patients, Studies to reconstitute such immunity, especially in people with acyclovir-resistant HSV, appear warranted.