Tremblay C, Merrill DP, Chou TC, Hirsch MS; Conference on Retroviruses and Opportunistic Infections.
Program Abstr 5th Conf Retrovir Oppor Infect Conf Retrovir Oppor Infect 5th 1998 Chic Ill. 1998 Feb 1-5; 5th: 198 (abstract no. 632).
Massachusetts General Hospital, Infectious Disease Unit, Harvard Medical School, Boston, MA.
The carbocyclic nucleoside 1592U89 (abacavir), a selective inhibitor of HIV reverse transcriptase (RT), was evaluated in two and three-drug combined regimens with stavudine (d4T) and with zidovudine (ZDV) and lamivudine (3TC) against HIV-1 replication in vitro. Using peripheral blood mononuclear cells infected with HIV-1, we evaluated drug interactions by the median-effect principle and the combination index technique against ZDV sensitive and -resistant clinical isolates (14a pre and 14a post). The IC50s for 1592 were 0.54 micromolar and 0.81 micromolar respectively for the ZDV-sensitive and ZDV-resistant isolates. With the sensitive isolate, synergistic interactions were seen with the combination of 1592 and d4T at concentrations greater than or equal to IC50, and with 1592 and ZDV at all concentrations tested. 1592 and 3TC combinations were synergistic at concentrations greater than IC 50. Synergistic interactions were also seen with the three-drug combination of 1592, ZDV, and 3TC against the ZDV-sensitive isolate. With the ZDV-resistant isolate, synergistic interactions were noted between 1592 and ZDV, and between 1592 and 3TC at concentrations greater than or equal to IC 50. Synergistic interactions were also observed with the 3-drug combination of 1592 + ZDV + 3TC against the ZDV-resistant isolate. In vitro studies with 1592-containing combinations against multi-drug resistant isolates are underway. These studies suggest a potential clinical utility for the three-drug combination of 1592, ZDV, and 3TC.
Publication Types:
Keywords:
- AIDS Vaccines
- Acquired Immunodeficiency Syndrome
- Anti-HIV Agents
- Dideoxynucleosides
- HIV
- HIV Infections
- HIV Protease Inhibitors
- HIV Seropositivity
- HIV-1
- In Vitro
- Lamivudine
- RNA-Directed DNA Polymerase
- Stavudine
- Zidovudine
- abacavir
Other ID:
UI: 102236216
From Meeting Abstracts