Functional T cell reconstitution and human immunodeficiency virus-1-specific cell-mediated immunity during highly active antiretroviral therapy.
Lymphoproliferative responses (LPRs) to recall antigens (Ags) and human immunodeficiency virus type 1 (HIV-1) Gag and frequencies of circulating HIV-1-specific cytotoxic T lymphocyte precursors (CTLps) were measured in 12 patients undergoing highly active antiretroviral therapy (HAART) after long-standing HIV-1 infection. LPRs to at least 1 recall Ag became detectable or increased in all patients during HAART. No significant LPRs to Gag-p24 were observed, whereas 4 of 8 patients tested presented with Gag-p17-specific LPRs. HIV-1-specific CTLp frequencies became measurable or increased early during therapy in 6 of 10 patients tested and were maintained or decreased thereafter. Increasing HIV-1-specific CTLp frequencies were seen only in association with partial HAART failure in 1 patient. In conclusion, restoration of CD4+ T lymphocyte responsiveness to recall Ags is achieved during HAART. The data provide evidence for limited HIV-1-specific CD4+ memory T cells during advanced HIV-1 infection and suggest that both CD4+ and CD8+ HIV-1-specific T cells are poorly stimulated when viral load is suppressed.
Pontesilli
O
O
Institute of Virology, Erasmus University Rotterdam, 3000 DR Rotterdam, The Netherlands. pontesilli@viro.fgg.eur.nl
Kerkhof-Garde
S
S
Notermans
D W
DW
Foudraine
N A
NA
Roos
M T
MT
Klein
M R
MR
Danner
S A
SA
Lange
J M
JM
Miedema
F
F
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015683:Gene Products, gag / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D054303:HIV Reverse Transcriptase / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D019380:Anti-HIV Agents; D015683:Gene Products, gag; D054303:HIV Reverse Transcriptase