TY - JOUR
T1 - Cytotoxic-T-cell responses, viral load, and disease progression in early human immunodeficiency virus type 1 infection
AU - Musey, Luwy
AU - Hughes, James
AU - Schacker, Timothy
AU - Shea, Theresa
AU - Corey, Lawrence
AU - Juliana Mcelrath, M.
PY - 1997/10/30
Y1 - 1997/10/30
N2 - Background: Early in human immunodeficiency virus type 1 (HIV-1) infection there is a decline in viral replication that has been attributed to host immunity, but the components of this response, particularly the ability of cytotoxic T lymphocytes to control viral burden and influence the outcome of disease, are poorly understood. Methods: We prospectively studied 33 patients with primary HIV-1 infection for HIV-specific activated cytotoxic T lymphocytes and memory cytotoxic T lymphocytes and compared these lymphocyte responses with changes in viral load and clinical status over the subsequent 18 to 24 months. Results: Soon after infection, activated HIV-specific cytotoxic T lymphocytes, mediated primarily by CD8+ cells, were detected in 17 of 23 patients (74 percent). Memory cytotoxic T lymphocytes were found in 6 of 6 patients tested (100 percent) during the first three months of infection and in 17 of 21 patients (81 percent) tested during the first six months. The frequencies of memory cytotoxic T lymphocytes varied markedly over time, but overall they declined over the first 6 to 8 months and then stabilized over the next 12 to 18 months. The patients with higher frequencies 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 frequencies median number of RNA copies per milliliter, 22,000 vs. 62,000; P=0.006. Patients with low frequencies of Env-specific memory cytotoxic T lymphocytes (or none) in early infection had a more rapid decline to less than 300 CD4+ cells per cubic millimeter (P = 0.05). Conclusions: In early HIV-1 infection, the induction of memory cytotoxic T lymphocytes, particularly those specific for Env, helps control viral replication and is associated with slower declines in CD4+ cell counts. Host cytolytic effector responses appear to delay the progression of HIV-1 disease.
AB - Background: Early in human immunodeficiency virus type 1 (HIV-1) infection there is a decline in viral replication that has been attributed to host immunity, but the components of this response, particularly the ability of cytotoxic T lymphocytes to control viral burden and influence the outcome of disease, are poorly understood. Methods: We prospectively studied 33 patients with primary HIV-1 infection for HIV-specific activated cytotoxic T lymphocytes and memory cytotoxic T lymphocytes and compared these lymphocyte responses with changes in viral load and clinical status over the subsequent 18 to 24 months. Results: Soon after infection, activated HIV-specific cytotoxic T lymphocytes, mediated primarily by CD8+ cells, were detected in 17 of 23 patients (74 percent). Memory cytotoxic T lymphocytes were found in 6 of 6 patients tested (100 percent) during the first three months of infection and in 17 of 21 patients (81 percent) tested during the first six months. The frequencies of memory cytotoxic T lymphocytes varied markedly over time, but overall they declined over the first 6 to 8 months and then stabilized over the next 12 to 18 months. The patients with higher frequencies 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 frequencies median number of RNA copies per milliliter, 22,000 vs. 62,000; P=0.006. Patients with low frequencies of Env-specific memory cytotoxic T lymphocytes (or none) in early infection had a more rapid decline to less than 300 CD4+ cells per cubic millimeter (P = 0.05). Conclusions: In early HIV-1 infection, the induction of memory cytotoxic T lymphocytes, particularly those specific for Env, helps control viral replication and is associated with slower declines in CD4+ cell counts. Host cytolytic effector responses appear to delay the progression of HIV-1 disease.
UR - http://www.scopus.com/inward/record.url?scp=0030831656&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030831656&partnerID=8YFLogxK
U2 - 10.1056/NEJM199710303371803
DO - 10.1056/NEJM199710303371803
M3 - Article
C2 - 9345075
AN - SCOPUS:0030831656
SN - 0028-4793
VL - 337
SP - 1267
EP - 1274
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 18
ER -