INTERIM RESULTS OF AMP720: A PHASE IIB PROSPECTIVE, RANDOMIZED, CONTROLLED STUDY EVALUATING THE IMMUNOMODULATORY ROLE OF AMPLIGEN (POLY I:POLY C12U) AGAINST HIV DURING STI
Background: Prolonged use of highly active antiretroviral therapy (HAART) has been associated with long term, potentially fatal, toxicities. Structured treatment interruption (STI) of HAART in chronically HIV-infected individuals to augment protective Th1 immune responses in order to achieve prolonged control of HIV-1 viremia has proved disappointing. Ampligen (AMP, poly I:poly C12U), a specifically mismatched dsRNA, is a biological response modifier with anti-HIV activity and strong Th1 imunomodulatory properties that has been shown to augment delayed-type hypersensitivity responses in HIV disease and may delay rebound of HIV-1 viremia during STI of HAART.
Methods: In this Phase IIB prospective, randomized controlled study, individuals with PCR<50 copies/ml and CD4≥400 are randomized 1:1 to undergo up to three STIs over 64 weeks with AMP, 400mg IV twice weekly, or without (CONTROL). STI is discontinued when PCR rebounds ≥5000 c/ml for 3 consecutive weekly determinations or ≥50,000 c/ml once.
Results: After a median duration of 9 months, CONTROL patients (n=10) have undergone first STI for a median duration 7 weeks and mean 13 weeks, while first STI in AMP patients (n=12) has been prolonged to a median 17 weeks and mean 27 weeks (p<0.04). Adverse events with AMP have been generally mild and self-limiting, and no adverse effects on lactic acid, insulin resistance, or hyperlipidemia have been observed while on AMP alone. CD8+ suppressor cells have increased greater in pts receiving AMP vs CONTROLS (p<0.05).
Conclusions: AMP (poly I:poly C12U) is generally well-tolerated and increases CD8+ suppressor cells which may, in part, explain the markedly prolonged duration of controlled HIV-1 viremia during STI of HAART.
The 2nd IAS Conference on HIV Pathogenesis and Treatment
" G. Blick , et al.
INTERIM RESULTS OF AMP720: A PHASE IIB PROSPECTIVE, RANDOMIZED, CONTROLLED STUDY EVALUATING THE IMMUNOMODULATORY ROLE OF AMPLIGEN (POLY I:POLY C12U) AGAINST HIV DURING STI.
The 2nd IAS Conference on HIV Pathogenesis and Treatment: