Maraviroc (Selzentry) Has Minimal Effect on Lipid Profiles

HIV and Hepatitis.com Coverage of the 15th Conference on Retroviruses and Opportunistic Infections (CROI 2008) February 3 - 6, 2008, Boston, MA
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Many antiretroviral drugs are associated with abnormal blood lipid levels, which adversely affect cardiovascular risk. However, the most recently approved antiretroviral classes - CCR5 entry inhibitor and integrase inhibitors - appear to have less effect on lipids.

As reported at the 15th Conference on Retroviruses and Opportunistic Infections (CROI 2008) last month in Boston, researchers compared the effects on lipids of the CCR5 antagonist maraviroc (Selzentry) and the NNRTI efavirenz (Sustiva) in the ongoing MERIT study.

MERIT is a randomized trial comparing the safety and efficacy of 300 mg twice-daily maraviroc vs 600 mg once-daily efavirenz, both in combination with AZT + 3TC (Combivir), in treatment-naive patients infected with only CCR5-tropic HIV, as determined by the Trofile assay. A total of 721 patients were randomized and received at least 1 dose of study medication. About 70% were men, about 55% were white, about 35% were black, and the median age was just over 35 years.

Fasting serum lipid levels were measured at baseline and at weeks 24 and 48 after starting therapy (or at early termination). The researchers compared median maximum changes (mg/dL) in total cholesterol (TC), high-density lipoprotein (HDL or "good") cholesterol, calculated low-density lipoprotein (LDL or "bad") cholesterol, TC-to-HDL ratio, and triglycerides (TG), as well as the proportion of patients exceeding borderline-high thresholds according to the 2001 National Cholesterol Education Program (NCEP) guidelines.

Results

• Baseline lipid values and percentages of patients exceeding NCEP thresholds at baseline were comparable between the 2 groups.

• Median maximum changes from baseline in TC, HDL, LDL, and TG were greater in the efavirenz group compared with the maraviroc group (P < 0.01).

• The median decrease in TC-to-HDL ratio was greater in the maraviroc group (P < 0.01).
• Though the percentages of patients exceeding NCEP thresholds at baseline were not different, these were highly statistically different for TC and LDL while on therapy, favoring maraviroc (P < 0.0001).

	Median baseline (mg/dL)		Median maximum change from baseline (mg/dL)		Percentage above NCEP threshold at baseline		Percentage above NCEP threshold on therapy
	MVC	EFV	MVC	EFV	MVC	EFV	MVC	EFV
TC	156	155	+6	+33**	7	6	5	18**
HDL	37	38	+7	+13**	�	�	�	�
LDL	92	88	-9	+20**	6	4	3	12**
TC-to-HDL ratio	4.2	4.0	-0.5	-0.4*	�	�	�	�
TG	106	104	-9	+20**	7	7	7	8

MVC = maraviroc; EFV = efavirenz

*P < 0.01; **P < 0.001

NCEP threshold values:

• TC > 199 mg/dL;

• LDL > 129 mg/dL;

• TG > 199 mg/dL.

Conclusion

Based on these findings, the authors concluded:

• Median maximum lipid increases in TC, HDL, LDL, and TG were greater for patients on efavirenz + Combivir.

• TC-to-HDL ratio decreased more in patients on maraviroc + Combivir, while the percentage of patients with TC and LDL above NCEP guideline thresholds was higher in the efavirenz + Combivir group.

• These data demonstrate that maraviroc has a minimal effect on lipid profiles and is at least as "lipid neutral" as efavirenz.

Orlando Immunology Ctr, Orlando, FL; Univ of Toronto, Canada; Community Research Initiative of New England, Boston, MA; Univ of New South Wales, Australia; Hosp Univ of Geneva, Switzerland; Pfizer Global R&D, New London, CT; Pfizer Inc, New York, NY.

3/11/08

Reference
E DeJesus, S Walmsley, C Cohen, and others. Fasted Lipid Changes after Administration of Maraviroc or Efavirenz in Combination with Zidovudine and Lamivudine for 48 weeks to Treatment-naive HIV-infected Patients. 15th Conference on Retroviruses and Opportunistic Infections (CROI 2008). Boston, MA. February 3-6, 2008.929.

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