AEGiS-14IAC: Antiviral activity of poly I:poly C12U as monotherapy in early HIV infection and in combination with antiretrovirals (ARV) in treatment experienced patients failing HAART.

14th International AIDS Conference

Barcelona, Spain - July 7-12, 2002

Antiviral activity of poly I:poly C12U as monotherapy in early HIV infection and in combination with antiretrovirals (ARV) in treatment experienced patients failing HAART.

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. LbPeB9011)

Mitchell W, Blick G, Strayer D, Cimoch P, Carter W
Vanderbilt University, Nashville, United States

BACKGROUND: Poly I:poly C12U, a specifically mismatched dsRNA, is a biological response modifier with anti-HIV activity that is synergistic with a majority of FDA approved ARV agents. Poly I:poly C12U has a novel mechanism of activating the intracellular antiviral mediators, 2-5A synthetase/RNase L.

METHOD: Poly I:poly C12U (400 mg IV twice weekly) was used as monotherapy in a prospective, open-label, phase II study in treatment naïve patients with CD4 > 400 cells/mm³ and HIV RNA > 4000 copies/ml. In addition, a Phase IIB prospective, randomized controlled study is being conducted using the same dosage level in treatment experienced patients with HIV RNA > 500 and < 30,000 copies/ml and CD4 cell count > 300 cells/mm³. The patients are randomized 1:1 to initially receive poly I:poly C12U in addition to stable background HAART or remain on HAART alone (CONTROL) for 24 weeks.

RESULTS: After a median duration of 4.5 months, poly I:poly C12U (n=7) patients on stable HAART have experienced a mean HIV RNA decrease of 0.50 log₁₀ copies/ml. Two patients (29%) have declined to <50 copies/ml (21 and 41 copies/ml at weeks 24 and 12, respectively). Patients on poly I:poly C12U monotherapy (n=8) had a decrease of 0.25 log₁₀ (p= 0.04) in HIV RNA after 24 weeks. Adverse events with poly I:poly C12U have been mild and self-limiting.

CONCLUSIONS: Initial results demonstrate that poly I:poly C12U is well tolerated and provides antiviral suppression when used as monotherapy or in combination with failing HAART regimens.

Keywords: AEGIS, Antiretroviral Therapy, Highly Active, HIV Infections, Poly I, HIV, CD4 Lymphocyte Count, Poly I-C, Anti-HIV Agents, RNA, Double-Stranded, Drug Therapy, Combination, Endoribonucleases, pppA(2'p5'A)n-dependent ribonuclease, Human, therapy, drug therapy

020707
LbPeB9011