STAPLETON JT, KLINZMAN D, OLAKANMI O, WUENSCHMANN S, SCHLESINGER LS, BRITIGAN BE; Interscience Conference on Antimicrobial Agents and Chemotherapy.
Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 1999 Sep 26-29; 39: 319 (abstract no. 934).
Univ. of Iowa and Iowa City VA Med. Ctr., Iowa City, IA.
BACKGROUND: Gallium nitrate (Ga) is a potent ribonucleotide reductase inhibitor which was previously shown to inhibit avian retroviruses. Although the mechanism of it's anti-retroviral activity was not elucidated, it is known that Ga inhibits cellular activation in a manner analogous to hydroxyurea (HU). Since Ga is administered to humans intravenously, and oral preparations are being developed, we evaluated Ga for it's anti-HIV activity, and compared it with HU.METHODS: Various concentrations of Ga or HU were added to 1 x 106 PHA/IL2 stimulated PBMC's 24 hours prior to infecton with HIV-1 stock virus. 16 hrs. following infection, cells were washed and culture supernatants were obtained 4 and 7 days post-infection. HIV p24 antigen production in culture supernatants was determined by ELISA. To determine if RT inhibitors were potentiated by Ga, zidovudine(zdv), ddI and ddC were also evaluated with and without Ga.RESULTS: Ga reproducibly inhibited HIV replication at concentrations which did not inhibit cellular proliferation or viability. Ga IC50 ranged from 4 to 10 uM, which was approximately 15-fold lower than HU (120 uM) in our culture system. Using sub-inhibitory concentrations of zdv, ddI and ddC, Ga potentiated the inhibitory effects of these nucleoside analogs. The addition of transferrin to the cell culture did not appear to have a significant effect on the antiviral activity of Ga.CONCLUSIONS: Ga was considerably more potent than HU in inhibiting HIV-1 replication in stimulated PBMC culture. This effect potentiated the effect of anti-HIV nucleoside RT inhibitors. Ga inhibits the same cellular target as HU although it does so by a different mechanism of action. Since the inhibitory concentration of Ga is achievable in humans, and the relative potency of Ga is greater than HU, additional studies of Ga appear warranted.
Publication Types:
Keywords:
- Acquired Immunodeficiency Syndrome
- Antiviral Agents
- Communicable Diseases
- Didanosine
- Gallium
- HIV Core Protein p24
- HIV Infections
- HIV Seropositivity
- HIV-1
- Humans
- Hydroxyurea
- In Vitro
- Zalcitabine
- Zidovudine
- gallium nitrate
- immunology
Other ID:
UI: 102246596
From Meeting Abstracts