1st International Workshop on HIV Drug Resistance & Treatment Strategies


25-28 June 1997, St. Petersburg, Florida, USA


PRELIMINARY GENOTYPIC ANALYSIS OF HIV-1 IN PLASMA FROM VOLUNTEERS RECEIVING REPEATED MULTIPLE DOSES OF MKC-442

Antiviral Therapy 1997;2 (Suppl 5):14 (abstract no. 22)

K Borroto-Esoda, DS Noel, CP Moxham and PA Furman
Triangle Pharmaceuticals, Durham, North Carolina, USA

Preliminary genotypic analysis of HIV-1 in plasma samples from patients receiving repeated multiple oral doses of MKC-442 are reported from an ongoing Phase IB double-blind, randomized, placebo-controlled study. Patients with CD4+ counts of ≥ 100 cells/ml and HIV-1 RNA ≥ 10,000 copies/ml were enrolled in one of six cohorts and given repeated oral doses of MKC-442 for up to 2 months. Patients were monitored for changes in viral load at baseline (day 0), and after 1 month (day 29) and 2 months (day 57) of therapy; viral load was also monitored 1 month after therapy was completed. HIV-1 in plasma samples from select patients in each cohort was analysed for genotypic changes using the Affymetrix Gene Chip technology. Genotypic changes associated with resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) were observed in HIV-1 virus from several patients during the course of therapy. Mutations at position 103 of the reverse transcriptase gene (K103N, K103R) were observed in some patients after 1 month (day 29) of therapy with MKC-442. A mutation at position 181 (Y181C) was also observed in HIV-1 virus isolated from a patient 1 month after therapy was completed. Peripheral blood mononuclear cells (PBMCs) obtained from this patient at day 0, day 29 and day 57 of treatment, and 1 month post-treatment, were co-cultured with uninfected donor PBMCs. Genotypic and phenotypic variations in the co-cultured virus samples will be presented.

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1997-06-25
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