Partial treatment interruption of protease inhibitors augments HIV-specific immune responses in vertically infected pediatric patients.
BACKGROUND
Although highly active antiretroviral therapy has significantly reduced morbidity and mortality in HIV-infected children, it often fails to completely suppress viral replication, thereby allowing the emergence of drug-resistant variants. Protease inhibitor (PI) based therapy has been hypothesized to depress cell-mediated immune responses by reducing antigen presentation.


OBJECTIVE
To determine the effects of partial treatment interruption (PTI) of PI on HIV-specific cellular immune responses in children.


METHODS
We conducted a retrospective longitudinal study of HIV-specific cellular immune responses in 13 children who were vertically infected with HIV. All had detectable plasma viremia and had undergone PTI for a median of 1.0 year (range, 0.41-3.35 years) while continuing nucleoside reverse transcriptase inhibitor and non-nucleoside reverse transcriptase inhibitor therapy.


RESULTS
No significant changes in viral load were observed in the immediate time-point before and during PTI (P = 0.84) as well as in the overall period before and during PTI (P = 0.17). CD4 T-cell levels declined slowly immediately before and during PTI (P = 0.07) as well as during the overall PTI period (P = 0.0002), but the rate of CD4 T-cell decline was not significantly increased during PTI. Immediate to PTI, HIV-specific CD4 and CD8 T-cell responses increased by 70% (P < 0.0001) and 92% (P < 0.0001), respectively, and CD4 and CD8 T-cell activation levels (P = 0.6834 and P = 0.6081, respectively) remained unchanged.


CONCLUSIONS
HIV-specific cellular immune responses are boosted in children who have interrupted PI-based therapy.
Legrand
Fatema A
FA
Gladstone Institute of Virology and Immunology, University of California, San Francisco, California 94158-2261, USA. flegrand@gladstone.ucsf.edu
Abadi
Jacob
J
Jordan
Kimberly A
KA
Davenport
Miles P
MP
Deeks
Steve G
SG
Fennelly
Glenn J
GJ
Wiznia
Andrew A
AA
Nixon
Douglas F
DF
Rosenberg
Michael G
MG
D000293:Adolescent; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000378:metabolism; D004334:Drug Administration Schedule; D005434:Flow Cytometry / Q000379:methods; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000635:transmission; D017320:HIV Protease Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D015497:HIV-1; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D016130:Immunophenotyping; D018445:Infectious Disease Transmission, Vertical; D008213:Lymphocyte Activation / Q000187:drug effects; D012189:Retrospective Studies; D019562:Viral Load
D016207:Cytokines; D017320:HIV Protease Inhibitors