ISSN 1472-4683. Published by i-Base.
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Simon Collins, HIV i-Base
One of the highlights from last months IAS conference in Toronto was the late-breaker results from the Phase II dose-finding MK-0518 integrase inhibitor vs efavirenz, with tenofovir/FTC. [1]
Similar virological responses were seen in all arms at week 24, but of note, significantly faster suppression, and greater decreases in viral load were seen in all MK-0518 arms at weeks 4-8. As a result of this study, the 400mg BID dose was selected. Ongoing EAP programmes already started in the US, and starting in October in the UK, will collect additional safety data for the fast-track approval application.
Further details from this treatment-naIve study were presented at ICAAC, showing that MK-0518 had a better lipid profile over 24 weeks in treatment naIve patients than efavirenz. [2]
Total cholesterol dropped slightly (by approximately -5mg/dL over the first 12 weeks and was sustained out to week 24, compared to increases of +20 mg/dL in the efavirenz arm.
LDL (bad cholesterol) dropped slightly (by around -5mg/dL over the first 12 weeks sustained out to week 24, compared to increases of +5 mg/dL and +10 mg/dL at 12 and 24 weeks in the efavirenz arm. Differences compared to efavirenz were statistically significant, but were probably too modest to lead to clinical benefit.
HDL (good cholesterol) increased more rapidly in the efavirenz arm (approximetely +6 mg/dL vs +1 mg/dL at 12 weeks) but differences reduced to approximately +4 and +2 respectively at week 24, and were not statistically significant.
Serum triglycerides remained close to baseline for the 100, 200 and 400 mg BD doses of MK-0518 out to week 24 and fell by ~50mg/dL in the 600mg BID arm, compared to an increase of approximately +50mg/dL over the first 12 weeks in the efavirenz, arm that were sustained out to week 24.
Table 1: Lipid changes after 24 weeks of MK-0518 or efavirenz
* p<0.05 compared to EFV
Several interaction studies involving MK-0518 were also presented at ICAAC:
References
Unless stated otherwise, all references are to the Programme and Abstracts of 46th ICAAC, 27-30 September 2006, San Francisco.
1. Markowitz M, Nguyen B-Y, Gotuzzo E et al. Potent antiretroviral
effect of MK-0518, a novel HIV-1 integrase inhibitor, as part of combination
ART in treatment-naIve HIV-1 infected patients. XVI International AIDS Conference,
Toronto, 2006. Late breaker abstract THLB0214. See HTB September 2006.
http://www.i-base.info/htb/v7/htb7-9/Integrase.html
2. Teppler H, Azrolan N, Chen J, et al. Differential effect of MK-0518 and
efavirenz on serum lipids an lipoproteins in antiretroviral therapy (ART)-naive
patients. 46th ICAAC. Abstract H-256a.
3. Wenning LA, Hanley H, Stone J, et al. Effect of tipranavir + ritonavir
on pharmacokinetics of MK-0518. 46th ICAAC. Abstract A-374.
4. Wenning LA, Friedman E, Kost JT, et al. Lack of a significant drug interaction
between MK-0518 and tenofovir disoproxil fumarate. 46th ICAAC. Abstract A-375.
5. Iwamoto M, Wenning LA, Petry AS, et al. Minimal effect of ritonavir and
efavirenz on pharmacokinetics of MK-0518. 46th ICAAC. Abstract A-373.
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