Structured treatment interruptions (STIs) in HIV-1 infected pediatric populations increases interferon gamma production and reduces viremia.
We assessed the effect of progressively longer antiretroviral structured treatment interruptions (STIs) starting with 3 days, increasing by 2 days in length each cycle on HIV-specific immune responses. As well, we correlated these responses with control of HIV viremia. Eight individuals became viremic and reached cycle 13 with an STI of > or =27 days. HIV-specific gamma-interferon production to inactivated HIV and vaccinia vectors expressing gag, env, nef, and pol increased (>10-fold) in six of eight subjects. Median plasma RNA levels peaked @ cycle 7 and declined to levels <10(4)cp/ml after cycle 10. In a subset of five who reached cycle 17, HIV-specific IFN-gamma frequencies increased from cycle 8 to cycle 17 with evidence of improved virologic control over comparable periods off antiretroviral therapy. This allowed us to conclude that exposure to autologous virus increased HIV-specific immune responses and decreased HIV RNA were seen in those who have had >13 interruptions, with STI intervals that exceeded 27 days.
Borkowsky
William
W
NYU School of Medicine, New York, NY, USA. borkow01@gcrc.med.nyu.edu
Yogev
Ram
R
Muresan
Petronella
P
McFarland
Elizabeth
E
Frenkel
Lisa
L
Fenton
Terry
T
Capparelli
Edmond
E
Moye
Jack
J
Harding
Paul
P
Ellis
Nina
N
Heckman
Barbara
B
Kraimer
Joyce
J
D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004334:Drug Administration Schedule; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D015497:HIV-1 / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology*; D012367:RNA, Viral / Q000097:blood; D013997:Time Factors; D019562:Viral Load; D014766:Viremia / Q000188:drug therapy* / Q000276:immunology
D019380:Anti-HIV Agents; D012367:RNA, Viral; D007371:Interferon-gamma