SEVERE GENITAL HERPES INFECTIONS IN HIV-INFECTED INDIVIDUALS WITH IMPAIRED HERPES-SIMPLEX VIRUS-SPECIFIC CD8-LYMPHOCYTE RESPONSES( CYTOTOXIC T)

The specific mechanisms underlying the varied susceptibility of HIV-in fected (HIV+) individuals to opportunistic infections (OI) are still i ncompletely understood, One hypothesis is that quantitative difference s in specific T cell responses to a colonizing organism determine the development of an AIDS-defining OI, We evaluated this hypothesis for h erpes simplex virus (HSV) infection, a common OI in HIVS patients, Usi ng limiting dilution analyses, the frequency of HSV-specific CD8(+) cy totoxic T lymphocyte precursors (pCTL) and proliferative precursors we re quantitated in peripheral blood mononuclear cells from 20 patients coinfected with HIV and HSV-2. The frequency of HSV-specific CD8(+) pC TL in HSV+HIV+ individuals was significantly lower than in HSV+HIV- in dividuals (1 in 77,000 vs, 1 in 6,000, P = .0005) and was not differen t 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 mi ld recurrences (1 in 170,000 vs, 1 in 26,000, P = .03), In contrast, n o significant difference was seen in proliferative precursor frequenci es between those patients with mild vs, severe genital herpes (1 in 3, 800 vs, 1 in 6,600, P > .5). Quantitative differences in pCTL frequenc y to HSV appear to be the most important host factor influencing the f requency and severity of HSV reactivation in HIV+ patients, Studies to reconstitute such immunity, especially in people with acyclovir-resis tant HSV, appear warranted.