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Nonnucleoside TMC-278 Slated for First-Line Use Looks Good Through 96 Weeks
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XVII International AIDS Conference
August 3-8, 2008
Mexico City
Mark Mascolini
Rilpivirine (TMC278), a nonnucleoside being developed for first-line therapy, sustained 48-week response rates through 96 weeks in a phase-2 comparison with efavirenz [1]. Certain side effects were more limited with rilpivirine than with efavirenz.
An international cast of investigators randomized 368 antiretroviral-naive people to start 25, 75, or 150 mg of rilpivirine once daily or standard-dose once-daily efavirenz plus two nucleosides--zidovudine/lamivudine in 76% and tenofovir/emtricitabine in 24%. One third of study participants were women, and just under half were Caucasian. Pretreatment viral load averaged about 70,000 copies in the combined rilpivirine groups and the efavirenz group, and starting CD4 count averaged about 200.
Using a time-to-loss-of-virologic-response analysis, the researchers charted similar sub-50-copy rates across the four treatment arms at 48 weeks, with a slight falloff in each arm through 96 weeks:
- Rilpivirine 25 mg (n = 93): 80% at week 48 and 76% at week 96
- Rilpivirine 75 mg (n = 95): 80% at week 48 and 72% at week 96
- Rilpivirine 150 mg (n = 91): 77% at week 48 and 71% at week 96
- All rilpivirine arms (n = 279): 79% at week 48 and 73% at week 96
- Efavirenz (n = 89): 81% at week 48 and 71% at week 96
Whereas 7 people dropped out of the rilpivirine groups by week 48, only 1 more quit by week 96. Six people stopped efavirenz by week 48 and 2 more by week 96.
Average CD4 counts climbed by equivalent amounts in all four treatment groups through 48 weeks and continued to climb in the next 48 weeks:
- Rilpivirine 25 mg: +122 cells at week 48 and +146 at week 96
- Rilpivirine 75 mg: +145 cells at week 48 and +172 cells at week 96
- Rilpivirine 150 mg: +143 cells at week 48 and +159 cells at week 96
- Efavirenz: +127 cells at week 48 and +160 cells at week 96
Rates of serious side effects were similar at 96 weeks in the combined rilpivirine and efavirenz groups (12.2% versus 14.6%), as were rates of grade 3 or 4 toxicities (27.2% versus 21.3%) and grade 3 or 4 lab abnormalities (26.5% versus 23.6%). Three side effects often seen with efavirenz arose less often in people taking rilpivirine: rash (21% versus 9%, P < 0.01), central nervous system problems, especially dizziness and sleepiness (48% versus 31%, P < 0.01), and abnormal dreams or nightmares (11% versus 3%, P < 0.05). Still, these findings indicate that central nervous system side effects may trouble a substantial minority of people taking rilpivirine.
Triglycerides fell an average of 9.9 mg/dL with rilpivirine while climbing 29.2 mg/dL with efavirenz. The total-to-high-density lipoprotein (HDL) cholesterol ratio did not change much in either treatment group (-0.4 with rilpivirine and -0.1 with efavirenz).
Reference
1. Santoscoy M, Cahn P, Gonsalez C, et al. TMC278 (rilpivirine), a next-generation NNRTI, demonstrates long-term efficacy and tolerability in ARV-naive patients: 96-week results of study C204. XVII International AIDS Conference. August 3-8, 2008. Mexico City. Abstract TUAB0103.
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