Additional side-effect data from a clinical trial of rilpivirine (TMC-278), Tibotec’s experimental non-nucleoside reverse transcriptase inhibitor (NNRTI), indicates that it causes minimal changes in lipid (fat) and glucose (sugar) levels over 48 weeks of treatment. The new data, reported at the fourth IAS Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2007) in Sydney, suggests that the drug may have a potential safety advantage over Sustiva.
Study C204 is a 96-week trial comparing three once-daily doses of rilpivirine to Sustiva, all in combination with Truvada (tenofovir plus emtricitabine) or Combivir (zidovudine plus lamivudine). Three hundred sixty-eight patients, in total, have been randomized to receive either Sustiva or one of three rilpivirine doses (all taken once a day).
The 48-week efficacy data, reported at the 14th Conference on Retroviruses and Opportunistic Infections this past February in Los Angeles, demonstrated that rilpivirine has comparable efficacy to Sustiva, the leading first-line NNRTI choice.
The objective of the analysis presented at IAS 2007 by Kiat Ruxrungtham, MD, of Chulalongkorn University in Bangkok, was to compare the metabolic side effects of both drugs. These included changes, over the 48-week period of the trial, in total cholesterol, “bad” LDL cholesterol, “good” HDL cholesterol, triglycerides, glucose and insulin resistance (which can lead to diabetes).
Changes in body shape, such as lipoatrophy, were not measured in the study.
All patients enrolled in the study were treatment-naïve, meaning that they had not taken any other HIV medications in the past. Approximately 33 percent of the patients participating in the study are women and roughly 45 percent are white.
After 48 weeks, a number of statistically significant differences were documented. These included a total cholesterol increase of 31 mg/dL in the Sustiva group, compared to 5 mg/dL in the combined rilpivirine group. LDL levels increased by 15 and 1 mg/dL and HDL increased by 12 and 5 mg/dL respectively.
Triglyceride levels dropped by 10 mg/dL in the rilpivirine group after 48 weeks, compared to an 18-mg/dL increase in the Sustiva group.
Fasting glucose levels among rilpivirine recipients increased by an average of 1 mg/dL, compared to a 3-mg/dL increase among those taking Sustiva.
The only metabolic parameters that did not differ significantly between the two groups after 48 weeks of treatment were the ratio of total cholesterol to HDL cholesterol and calculated insulin resistance.
Dr. Ruxrungtham and his colleagues concluded that “[rilpivirine] resulted in minimal changes in lipid profiles and may have a potential benefit versus [Sustiva].”
They added that two 96-week phase III studies of rilpivirine are slated to being at this fall.
Source:
Ruxrungtham K, Bellow N, Morales-Ramirez J, et al. The metabolic profile of TMC-278, an investigational non-nucleoside reverse transcriptase inhibitor (NNRTI) [Abstract TUAB106]. Fourth IAS Conference on HIV Pathogenesis, Treatment and Prevention, Sydney, 2007.
