Differential Effect of MK-0518 and Efavirenz on Serum Lipid Levels

Given that several antiretroviral agents are associated with hyperlipidemia, researchers conducted a study to evaluate changes in serum lipid levels associated with the novel integrase inhibitor MK-0518.

This Phase II study evaluated 4 doses of MK-0518 vs efavirenz (Sustiva/Stocrin), both combined with tenofovir/3TC (Truvada), in antiretroviral-naive HIV positive patients with HIV RNA levels of at least 5000 copies/mL and CD4 cell counts of at least 100 cells/mm3. Changes from baseline in fasting serum cholesterol (SC), triglycerides (TG), LDL (low-density lipoprotein, or "bad') cholesterol, and HDL (high-density lipoprotein, or "good") cholesterol were assessed after 24 weeks of treatment.

Results

Baseline lipid levels were similar in all treatment groups.

Mean changes from baseline in serum lipid levels (in mg/dL) at 24 weeks are shown in the table below:

	Treatment**	N	Baseline	Change (95% CI)
SC	MK-0518 100 mg bid	39	168	-7* (-14, 0)
	MK-0518 200 mg bid	34	161	-2* (-11, 8)
	MK-0518 400 mg bid	40	168	-7* (-15, 2)
	MK-0518 600 mg bid	35	162	-4* (-12, 5)
	Efavirenz 600 mg qd	36	170	+19 (8, 30)
TG	MK-0518 100 mg bid	39	129	+2 (-22, 26)
	MK-0518 200 mg bid	34	110	-5* (-20, 9)
	MK-0518 400 mg bid	40	127	-2* (-23, 18)
	MK-0518 600 mg bid	35	155	-43* (-87, 1)
	Efavirenz 600 mg qd	36	128	+47 (-1, 96)
N= number of patients with data * p-value < 0.05 for comparison to efavirenz ** MK-0518 and efavirenz were given in combination with tenofovir/3TC

Serum cholesterol and triglyceride values were relatively unchanged following MK-0518 therapy.

In contrast, efavirenz was associated with increases in both serum cholesterol and triglycerides.

LDL levels fell slightly in the MK-0518 arms, while rising in the efavirenz arm.

HDL levels increased in both the MK-0518 and efavirenz arms.

Conclusion

The researchers concluded that, "MK-0518, when dosed at 100 mg to 600 mg [twice-daily] in combination with [tenofovir/3TC] for 24 weeks in treatment-naive HIV infected patients was not associated with increases in serum cholesterol, LDL cholesterol, or triglycerides, which contrasts significantly with lipid changes associated with treatment with efavirenz."

Merck & Co., Inc., North Wales, PA.

10/10/06

Reference
H Teppler, N Azrolan, J Chen, and others. Differential Effect of MK-0518 and Efavirenz on Serum Lipids and Lipoproteins in Antiretroviral Therapy (ART)-naive Patients. 46th ICAAC. San Francisco, CA. September 27-30, 2006. Abstract H-256a.

_______________

Conference
Main Page