Partial treatment interruption of protease inhibitors augments HIV-specific immune responses in vertically infected pediatric patients

AIDS. 2005 Oct 14;19(15):1575-85. doi: 10.1097/01.aids.0000186816.99993.8e.

Abstract

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.

Objectives: 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.

Conclusion: HIV-specific cellular immune responses are boosted in children who have interrupted PI-based therapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Antiretroviral Therapy, Highly Active
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Child
  • Child, Preschool
  • Cytokines / metabolism
  • Drug Administration Schedule
  • Flow Cytometry / methods
  • HIV Infections / drug therapy
  • HIV Infections / immunology*
  • HIV Infections / transmission
  • HIV Protease Inhibitors / administration & dosage*
  • HIV Protease Inhibitors / therapeutic use
  • HIV-1*
  • Humans
  • Immunity, Cellular / drug effects
  • Immunophenotyping
  • Infectious Disease Transmission, Vertical
  • Lymphocyte Activation / drug effects
  • Retrospective Studies
  • Viral Load

Substances

  • Cytokines
  • HIV Protease Inhibitors