Incomplete immune reconstitution after initiation of highly active antiretroviral therapy in human immunodeficiency virus-infected patients with severe CD4+ cell depletion.
Immune function was observed for 144 weeks in 643 human immunodeficiency virus (HIV)-infected subjects who (1) had nadir CD4+ cell counts of <50 cells/mm3, followed by a sustained increase to > or =100 cells/mm3 after the initiation of HAART, and (2) were enrolled in a randomized trial of continued azithromycin prophylaxis versus withdrawal for prevention of Mycobacterium avium complex disease. The median CD4+ cell count was 226 cells/mm3 at entry and 358 cells/mm3 at week 144. Anergy (80.2% of patients) and lack of lymphoproliferative response to tetanus toxoid (TT; 73%) after immunization and impaired antibody responses after receipt of hepatitis A (54%) and TT (86%) vaccines were considered to be evidence of impaired immune reconstitution. Receipt of azithromycin did not have an effect on CD4+ cell count but was associated with higher rates of delayed-type hypersensitivity responses to TT (25% of subjects who received azithromycin vs. 15% of those who did not; P=.009) and mumps skin test antigen (29% vs. 17%; P=.001). Although the subjects had only partial responses to immune function testing, the rate of opportunistic infections was very low, and none of the tests was predictive of risk.
Lederman
Howard M
HM
Eudowood Division of Pediatric Allergy and Immunology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. hlederm1@jhem.jhmi.edu
Williams
Paige L
PL
Wu
Julia W
JW
Evans
Thomas G
TG
Cohn
Susan E
SE
McCutchan
J Allen
JA
Koletar
Susan L
SL
Hafner
Richard
R
Connick
Elizabeth
E
Valentine
Fred T
FT
McElrath
M Juliana
MJ
Roberts
Norbert J
NJ
Currier
Judith S
JS
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000276:immunology; D000328:Adult; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000907:Antibodies, Bacterial / Q000097:blood; D023241:Antiretroviral Therapy, Highly Active; D000998:Antiviral Agents / Q000627:therapeutic use*; D017963:Azithromycin / Q000627:therapeutic use; D015415:Biomarkers / Q000032:analysis; D018791:CD4 Lymphocyte Count; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000276:immunology*; D015497:HIV-1 / Q000302:isolation & purification; D035922:Hepatitis A Antibodies / Q000097:blood; D022362:Hepatitis A Vaccines / Q000008:administration & dosage; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009109:Mumps virus / Q000276:immunology; D015270:Mycobacterium avium-intracellulare Infection / Q000209:etiology / Q000517:prevention & control; D012367:RNA, Viral / Q000097:blood; D013745:Tetanus Toxoid / Q000008:administration & dosage / Q000276:immunology
D000900:Anti-Bacterial Agents; D000907:Antibodies, Bacterial; D000998:Antiviral Agents; D015415:Biomarkers; D035922:Hepatitis A Antibodies; D022362:Hepatitis A Vaccines; D012367:RNA, Viral; D013745:Tetanus Toxoid; D017963:Azithromycin