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Abstract
Short-term monotherapy with UK-453,061, a novel NNRTI, reduces viral load in HIV infected patients
Fätkenheuer G.1, Staszewski S.2, Plettenburg A.3, Hackman F.4, Layton G.4, McFadyen L.4, Davis J.4, Jenkins T.4
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.
4th IAS Conference on HIV Pathogenesis, Treatment and Prevention
Abstract no.
WESS202
Suggested Citation
"FätkenheuerG., et al.
Short-term monotherapy with UK-453,061, a novel NNRTI, reduces viral load in HIV infected patients.
Special session:
4th IAS Conference on HIV Pathogenesis, Treatment and Prevention:
Abstract no.
WESS202"
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