AEGiS-11IAC: Synergistic antagonism of HIV reverse transcriptase activity by monoclonal antibodies in the presence of NNRTI's.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

Synergistic antagonism of HIV reverse transcriptase activity by monoclonal antibodies in the presence of NNRTI's.

Int Conf AIDS 1996 Jul 7-12; 11:438 (abstract no. Pub.A.1002)
Gu Z, Parniak MA, Wainberg MA; McGill University AIDS Centre-Jewish General Hospital, Montreal, Canada. Fax: (514) 340-7537.

OBJECTIVE: To assess the ability of a monoclonal antibody termed 1E8 to impact on HIV reverse transcriptase (RT) activity in the presence of both nucleoside triphosphate (ddNTP) inhibitors of RT and non-nucleoside RT inhibitors (NNRTI).

METHODS: Cell-free RT assays were performed with all 4 dNTPs plus 1E8 MAb in the presence or absence of various ddNTPs or NNRTI's.

RESULTS: 1E8 MAb antagonized inhibition of RT activity mediated by AZTTP and ddCTP. However, an additive/synergistic inhibition of RT polymerase activity was noted when 1E8 was studied together with the non-nucleoside RT inhibitors (NNRTI), Nevirapine and Delavirdine. Chain elongation/dNTP incorporation studies using an HIV-1 genome-derived heteropolymeric template, and either oligodeoxynucleotide or tRNALys.3 as primer, yielded results consistent with the above observations. 1E8 also increased pausing at certain sites during synthesis of (-) strong-stop DNA, regardless whether ddNTP and NNRTI inhibitors were present or not.

CONCLUSIONS: Combinations of 1E8 MAb, to be potentially used in intracellular immunization protocols, and NNRTIs may have therapeutic value.

Keywords: AEGIS, RNA-Directed DNA Polymerase, Delavirdine, Nevirapine, Reverse Transcriptase Inhibitors, Thymine Nucleotides, Zidovudine, HIV-1, Antibodies, Monoclonal, Anti-HIV Agents, DNA, Viral, Templates, Genetic, 3'-azido-3'-deoxythymidine 5'-triphosphate, strong-stop DNA, genetics, ICA11

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PubA1002