CYTOTOXIC-T-CELL RESPONSES, VIRAL LOAD, AND DISEASE PROGRESSION IN EARLY HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION

Background Early in human immunodeficiency virus type 1 (HIV-1) infect ion there is a decline in viral replication that has been attributed t o host immunity, but the components of this response, particularly the ability of cytotoxic T lymphocytes to control viral burden and influe nce the outcome of disease, are poorly understood. Methods We prospect ively studied 33 patients with primary HIV-1 infection for HIV-specifi c activated cytotoxic T lymphocytes and memory cytotoxic T lymphocytes and compared these lymphocyte responses with changes in viral load an d clinical status over the subsequent 18 to 24 months. Results Soon af ter infection, activated HIV-specific cytotoxic T lymphocytes, mediate d primarily by CD8+ cells, were detected in 17 of 23 patients (74 perc ent). Memory cytotoxic T lymphocytes were found in 6 of 6 patients tes ted (100 percent) during the first three months of infection and in 17 of 21 patients (81 percent) tested during the first six months. The f requencies of memory cytotoxic T lymphocytes varied markedly over time , but overall they declined over the first 6 to 8 months and then stab ilized over the next 12 to 18 months. The patients with higher frequen cies of Env-specific memory cytotoxic T lymphocytes had a median level of plasma HIV-1 RNA about one third that of the patients with lower f requencies (median number of RNA copies per milliliter, 22,000 vs. 62, 000; P=0.006). Patients with low frequencies of Env-specific memory cy totoxic T lymphocytes (or none) in early infection had a more rapid de cline to less than 300 CD4+ cells per cubic millimeter (P=0.05). Concl usions In early HIV-1 infection, the induction of memory cytotoxic T l ymphocytes, particularly those specific for Env, helps control viral r eplication and is associated with slower declines in CD4+ cell counts. Host cytolytic effector responses appear to delay the progression of HIV-1 disease. (C) 1997, Massachusetts Medical Society.