4th International Workshop on HIV Drug Resistance & Treatment Strategies


Sitges, Spain, 12–16 June 2000


SHORT-TERM MONOTHERAPY OF DAPD IN HIV-INFECTED PATIENTS

Antivir Ther. 2000 Jun 12-16; 5 (Suppl. 3):7 (Abstract 9

S Deeks1, H Kessler2, J Eron3, M Thompson4, F Raffi5 J Jacobson6, N Sista7, J Bigley7 and F Rousseau7
1UCSF, San Francisco, Calif., USA; 2Chicago Center for Clinical Research, Chicago, Ill., USA; 3University of North Carolina, Chapel Hill, N.C., USA; 4AIDS Research Cons. Of Atlanta, Atlanta, Ga., USA; 5Hotel Dieu-CHU Nantes, France; 6Mount Sinai Medical Center, New York, N.Y., USA; and 7Triangle Pharmaceuticals, Durham, N.C., USA

DAPD is a novel dioxolane guanosine analogue that is de-aminated by ADA to DXG, producing in vitro activity against strains of HIV resistant to drugs such as zidovudine, lamivudine and abacavir. In a non- randomized Phase I/II study, HIV-infected treatment-naïve patients received the following twice-daily doses of DAPD: 25, 100, 200, 300 or 500 mg. The median baseline CD4 count of patients in all dose cohorts ranged from 307 to 551 cells/mm3. The mean viral load in all dose cohorts at baseline ranged from log10 3.96 to log10 4.73. The maximum median reduction in HIV viral load was 0.5 (n=6), 1.0 (n=6), 1.14 (n=5), 1.5 (n=6), and 1.46 (n=6) log10 at 25, 100, 200, 300 and 500 mg twice daily dose of DAPD, respectively. The HIV genotypic profile from patients’ plasma at day 15 was compared to that at baseline. No genetic changes in the RT coding regions have been seen between pre- and post-treatment HIV genotypes with 15 days of DAPD monotherapy. All doses of DAPD tested were well tolerated. These results suggest a dose-dependent clinical antiviral activity of DAPD against HIV, a good short-term tolerability profile, and the absence of resistance mutations in a 15-day monotherapy study. These data warrant further clinical development of this novel molecule.

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2000-06-12
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