Long-term protease inhibitor-containing therapy results in limited improvement in T cell function but not restoration of interleukin-12 production in pediatric patients with AIDS.
This study investigated whether immune restoration occurred in 26 human immunodeficiency virus (HIV) type 1-infected children treated first with indinavir for 16 weeks and then with combination antiretroviral therapy for >2 years. Compared with baseline, a significant, although modest, decrease in virus loads (maximum median, -0.86 log(10)) and increase in the number of CD4(+) lymphocytes, especially naive cells, were observed at several time points after 2 years. A maximum of 7% of treated children achieved undetectable viremia. There was a marked increase in the proliferative response and skin reactivity to recall antigens. However, responses to an HIV antigen remained depressed, and the production of interleukin-12 remained unchanged and abnormally low. The magnitude of virus suppression did not correlate with these measures of functional immune reconstitution. These findings suggest that long-term nonsuppressive antiretroviral therapy can induce limited improvement in immune function in pediatric AIDS patients and that the effect of suppressive treatments should be investigated.
Chougnet
C
C
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA. chougnet@ihmi.edu
Jankelevich
S
S
Fowke
K
K
Liewehr
D
D
Steinberg
S M
SM
Mueller
B U
BU
Pizzo
P A
PA
Yarchoan
R
R
Shearer
G M
GM
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology; D000293:Adolescent; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D015488:HIV Antigens / Q000097:blood; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D006801:Humans; D019469:Indinavir / Q000627:therapeutic use; D018664:Interleukin-12 / Q000096:biosynthesis*; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D010835:Phytohemagglutinins / Q000097:blood; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load; D015215:Zidovudine / Q000627:therapeutic use
D019380:Anti-HIV Agents; D015488:HIV Antigens; D017320:HIV Protease Inhibitors; D010835:Phytohemagglutinins; D018664:Interleukin-12; D019259:Lamivudine; D015215:Zidovudine; D019469:Indinavir