Potent antiretroviral therapy of primary human immunodeficiency virus type 1 (HIV-1) infection: partial normalization of T lymphocyte subsets and limited reduction of HIV-1 DNA despite clearance of plasma viremia.
Antiretroviral therapy commenced during primary human immunodeficiency virus type 1 (HIV-1) infection (PHI) may limit the extent of viral replication and prevent early loss of HIV-specific CD4 lymphocyte function. We studied the effect of current standard therapy (2 nucleoside analogues and a protease inhibitor) in 16 patients with symptomatic PHI. In the 13 patients who completed 1 year of treatment, plasma HIV RNA was <50 copies/mL and median CD4 cell counts were comparable to HIV-uninfected controls, with naive (CD45RA+CD62L+), primed (CD45RO+), and T cell receptor Vbeta subsets all within normal ranges. However, HIV-1 DNA levels in treated and untreated PHI patients were similar. Furthermore, CD8 cell counts remained elevated, including activated (CD38+HLA-DR+), replicating (Ki-67+), and cytotoxic (perforin+CD28-) lymphocytes. In conclusion, early antiretroviral therapy resulted in clearance of viremia and prevented loss of crucial CD4 subsets. The persistence of HIV-1 DNA together with increased CD8 T lymphocyte turnover and activation indicate continued expression of viral antigens.
Centre for Immunology, St. Vincent's Hospital, UNSW, Darlinghurst, Australia 2010 Australia. J.Zaunders@cfi.unsw.edu.au
J J
JJ
Zaunders
P H
PH
Cunningham
A D
AD
Kelleher
G R
GR
Kaufmann
A B
AB
Jaramillo
R
R
Wright
D
D
Smith
P
P
Grey
J
J
Vizzard
A
A
Carr
D A
DA
Cooper
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015331:Cohort Studies; D004279:DNA, Viral / Q000097:blood; D004359:Drug Therapy, Combination; D015483:HIV Antibodies / Q000097:blood; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D019469:Indinavir / Q000627:therapeutic use; D019259:Lamivudine / Q000627:therapeutic use; D007963:Leukocytes, Mononuclear / Q000821:virology; D008213:Lymphocyte Activation; D008297:Male; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014766:Viremia / Q000188:drug therapy / Q000821:virology; D015215:Zidovudine / Q000627:therapeutic use
D019380:Anti-HIV Agents; D004279:DNA, Viral; D015483:HIV Antibodies; D012367:RNA, Viral; D019259:Lamivudine; D015215:Zidovudine; D019469:Indinavir