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Short-term monotherapy with UK-453,061, a novel NNRTI, reduces viral load in HIV infected patients
Presented by Tim Jenkins, .
Fätkenheuer G.1, Staszewski S.2, Plettenburg A.3, Hackman F.4, Layton G.4, McFadyen L.4, Davis J.4, Jenkins T.4
1Cologne University, Cologne, Germany, 2JH Goethe University, Frankfurt, Germany, 3Institute for Interdisciplinary Infectiology, Hamburg, Germany, 4Pfizer Global R & D, Sandwich, United Kingdom
Objectives: UK-453,061 is a NNRTI with potent anti-HIV activity, displaying balanced activity against both wild-type and clinically significant NNRTI-resistant viruses in vitro. Studies in healthy volunteers demonstrate that it is safe and well tolerated in both single and multiple dose studies. Short-term monotherapy studies were conducted in HIV patients to evaluate the effect on viral load and the relationship between viral load reduction and PKPD parameters.
Methods: 48 patients with CD4 count >250 and viral load >5000 copies/ml received UK-453,061 or placebo for 7 days and were followed up until day 40. To evaluate QD vs. BID dosing regimens, doses of 10, 30, 100 and 500mg BID and 100, 500 and 750mg QD UK-453,061 were chosen. Viral load, UK-453,061 plasma concentration and clinical safety evaluations, including laboratory safety tests were performed.
Results: UK-453,061 was well-tolerated and plasma concentrations were similar to those seen in healthy volunteers. Day 8/nadir mean viral load reductions of 0.3/0.4, 0.8/1.0, 1.3/1.6 and 1.6/1.9 log10 were seen for doses of 10, 30, 100 and 500mg BID, respectively. QD doses of 100, 500 and 750mg resulted in day 8/nadir mean viral load reductions of 0.9/1.1, 1.7/1.7 and 1.8/2.0 log10, respectively.
Conclusions: UK-453,061 was safe and well tolerated at all doses examined in this patient population. Doses ³ 200mg/daily resulted in similar viral load reductions, with a mean decrease from baseline HIV RNA nadir of ³ 1.6 log10. These results indicate that further evaluation of UK-453,061 for the treatment of HIV infection is merited.
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