ANDERSSON E, HORAL P, SVENNERHOLM B; Interscience Conference on Antimicrobial Agents and Chemotherapy (41st : 2001 : Chicago, Ill.).

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2001 Dec 16-19; 41: abstract no. I-1757.

Clinical Virology, Gothenburg, Sweden

BACKGROUND: Pre-clinical studies have shown that short peptides can inhibit the replication of HIV-1, possibly by interfering with capside formation. Since development of resistance is a major problem of antiretroviral drugs, it is of importance to investigate whether HIV-1 isolates exhibiting resistance to licensed anti-retroviral drugs are fully susceptible to GPG-NH2, and whether in vitro resistance to GPG-NH2 can be induced. METHODS: In all, 50 isolates with one or more mutations indicative of resistance to drugs of the NRTI and/or PI classes were evaluated for IC50 against GPG-NH2 in peripheral blood monocytes. The obtained IC50 values were compared to those found in non-resistant HIV. A laboratory strain of HIV-1 (HTLV-IIIB) was propagated in the T-cell line H9. By gradually increasing the concentration of Lamivudine and GPG-NH2, attempts to select resistant variants were performed. Resistance was defined by rapidly increasing IC50-values and confirmed through gene sequencing. RESULTS: No significant increase of GPG-NH2 IC50, as compared to wild type virus, in HIV-1 isolates resistant to one or more NRTI and PI drugs could be detected. After six passages resistance to Lamivudine was established; the IC50 increased more than 50.000 times and the resistant virus showed a 184Met Val mutation. After 16 passages with GPG-NH2 no increase in IC50 could be detected. CONCLUSIONS: Pre-existing resistance to NRTI or PI does not seem to influence the efficacy of GPG-NH2 in vitro. Also, development of resistance to GPG-NH2 does not occur as easily in vitro as to the NRTI Lamivudine. The observed in vitro findings indicate that this new class of antretroviral drug might be beneficiary in treating HIV-1 infection.

Publication Types:

• Meeting Abstracts

Keywords:

• Amides
• HIV Infections
• HIV Protease Inhibitors
• HIV-1
• In Vitro
• Lamivudine
• Oligopeptides
• Protease Inhibitors
• Selection (Genetics)
• genetics
• glycylprolylglycine amide
• reverse transcriptase, Human immunodeficiency virus 1

Other ID:

• GWAIDS0029025

UI: 102268657

From Meeting Abstracts