CD8-CELL-MEDIATED SUPPRESSION OF HIV REPLICATION IN THE FIRST YEAR OFLIFE - ASSOCIATION WITH LOWER VIRAL LOAD AND FAVORABLE EARLY SURVIVAL( T)

Objective and design: To study the role and development of non-cytotox ic CD8+ T-cell-mediated suppression of HIV replication in early perina tal HIV infection in a prospective study of vertically infected infant s. CD8 T-cell-mediated. HIV suppression was measured several times dur ing the first year of life and correlated with viral load, cytotoxic T -cell (CTL) activity, in vitro antibody production (IVAP) and clinical outcome. Methods: CD8+ T-cell-mediated HIV suppression was measured b y comparing the amount of p24 antigen produced by endogenously infecte d lymphocytes with cultures of the same number of autologous CD4+ T ce lls from which CD8+ cells were removed immunomagnetically. CD8 viral s uppressive activity (VSA) was defined as a greater than or equal to 50 % reduction in p24 antigen in the cultures containing CD8+ cells. Resu lts: CD8+ T-cell-mediated HIV VSA was detected, in 11/16 infants in th e first year of life, including six/nine infants studied before 6 mont hs and as early as 3 weeks of age. Infants who demonstrated CD8 VSA ha d a lower early peak and 6-month 'setpoint' plasma HIV RNA concentrati on than infants who lacked CD8 VSA [1.51 versus 4.94 and 0.094 versus 0.639 x 10(6) copies/ml, respectively, and higher CD4 percentage at 1 year of age. Survival of infants lacking CD8 VSA (four/six were rapid progressors) was shorter than for infants who demonstrated CD8 VSA (no ne out of 10 were rapid progressors). CD8 VSA was present before CTL a nd before or at the same time as IVAP in two of two and 11 of 14 infan ts studied, respectively. Conclusions: CD8+ T-cell-mediated VSA can be demonstrated in a large proportion of HIV-infected infants early in t he course of infection. This non-cytolytic HIV-suppressive immune resp onse appears to play an important protective role in the early control of perinatal HIV infection at a time when other immune responses are either absent or deficient.