Planned multiple exposures to autologous virus in HIV type 1-infected pediatric populations increases HIV-specific immunity and reduces HIV viremia

William Borkowsky*, Ram Yogev, Petronella Muresan, Elizabeth McFarland, Lisa Frenkel, Terry Fenton, Edmund Capparelli, Jack Moye, Paul Harding, Nina Ellis, Barbara Heckman, Joyce Kraimer

*Corresponding author for this work

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

We tested to determine if planned multiple exposures to autologous HIV in pediatric patients with HIV-1 infection will induce cellular immunity that controls viremia. A prospective multicenter study of aviremic pediatric patients on highly active antiretroviral therapy who underwent progressively longer antiretroviral treatment interruptions in cycles starting with 3 days, increasing by 2 days in length each consecutive cycle, was conducted. Eight individuals became viremic and reached Cycle 13 or greater with an "off-therapy" interval of ≥27 days. HIV-specific interferon-γ (IFN-γ) production to inactivated HIV and vaccinia vectors expressing gag, env, nef, and pol increased (>10-fold) from baseline in six of eight subjects. The HIV-specific lymphoproliferative response as measured by the median stimulation index (SI) increased in the treatment group from 1 at baseline to 16, 12, 4, and 3 at Cycles 7, 10, 13, and 17, respectively. Median plasma RNA levels peaked at Cycle 7 (4.45 log) and declined to levels <104 cp/ml after Cycle 10 (4.1, 3.5, and 3.4 at Cycles 10, 13, and 17). In a subset of five patients who reached Cycle 17, HIV-specific IFN-γ frequencies were 4- to 30-fold higher and median RNA levels were 0.32-2.10 (median 1.3) log lower than at comparable days off treatment at Cycle 8 (17 days off therapy). A second group of children, not undergoing drug interruption, did not develop significant increases in either HIV-specific IFN-γ production or SI. Increased HIV-specific immune responses and decreased HIV RNA were seen in those children who have had >10 cycles of antiretroviral discontinuations of increasing durations acting as autologous virus vaccinations. Other studies may have failed due to an insufficient number of exposures to HIV; most of the studies had fewer than six drug interruptions.

Original languageEnglish (US)
Pages (from-to)401-411
Number of pages11
JournalAIDS research and human retroviruses
Volume24
Issue number3
DOIs
StatePublished - Mar 1 2008

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Infectious Diseases

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