Rilpivirine (TMC278) Causes Less Blood Lipid Elevation than Efavirenz (Sustiva)

Blood fat elevations, a potential side effect seen with some antiretroviral drugs, are associated with an increased risk of cardiovascular disease.

At the recent 4th International AIDS Society Conference on HIV Treatment, Pathogenesis, and Prevention in Sydney, Australia (July 22-25, 2007), researchers reported on blood lipid changes in patients receiving Tibotec's experimental next-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine (TMC278).

In studies to data, rilpivirine has demonstrated potent and sustained anti-HIV activity in treatment-naive patients. In the present analysis, metabolic profiles -- fasting lipid levels, blood glucose, and insulin sensitivity -- were assessed and compared among subjects taking rilpivirine or efavirenz (Sustiva) in the ongoing TMC278-C204 trial.

In this trial, 368 antiretroviral-naive patients (33% women, median age 35 years) were randomly assigned to receive rilpivirine at doses of 25, 75, or 150 mg once daily or else efavirenz. All subjects also took 2 NRTIs (76% AZT/3TC, 24% tenofovir/emtricitabine). As previously reported,rilpivirine and efavirenz demonstrated similar virological efficacy at 48 weeks.

Results

• There were no significant differences in metabolic parameters between the different rilpivirine dose groups.

• Mean increases from baseline in total cholesterol, low-density lipoprotein (LDL or "bad") cholesterol, and triglycerides were significantly lower among patients taking rilpivirine (all dose groups combined) compared with those taking efavirenz.

- total cholesterol: +5 vs +31 mg/dL, respectively;
- LDL cholesterol: +1 vs +15 mg/dL, respectively;
- triglycerides: -10 vs +18 mg/dL, respectively.

• However, protective high-density lipoprotein (HDL or "good") cholesterol also increased less in the rilpivirine group compared with the efavirenz group (+5 vs +12 mg/dL).

• The ratio of total cholesterol to HDL was not significantly different between the rilpivirine and efavirenz groups.

• Fasting blood glucose rose by 1 mg/dL in the rilpivirine group and 3 mg/dL in the efavirenz group.

• However, insulin resistance as assessed by HOMA-IR did not differ significantly between the 2 groups.

Conclusion

"Higher total cholesterol, LDL cholesterol and triglycerides were observed with efavirenz than with TMC278," the researchers concluded. "There were minimal changes from baseline in glucose and insulin sensitivity, which were not significantly different between TMC278 and efavirenz."

Thai Red Cross AIDS Research Centre, Bangkok, Thailand; Southwest Infectious Disease Associates, Dallas, TX; Clinical Research, San Juan, Puerto Rico; Hospital Heliopolis, São Paulo, Brazil; Centro de Referência e Treinamento DST-AIDS, São Paulo, Brazil; Makerere University, Kampala, Uganda; Tibotec BVBA, Mechelen, Belgium; Tibotec Inc., Yardley, PA.

08/10/07

Reference
K Ruxrungtham, N Bellos, J Morales-Ramirez, and others. The metabolic profile of TMC278, an investigational non-nucleoside reverse transcriptase inhibitor (NNRTI). 4th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention. Sydney, Australia, July 22-25, 2007. Abstract TUAB105.