Rilpivirine Is Associated with Less Blood Fat Elevation than Efavirenz


People with HIV who started first-line treatment with a regimen containing rilpivirine (Edurant, also in the Complera coformulation) had smaller blood lipid increases and were less likely to have abnormal levels than those who started on efavirenz (Sustiva, also in the Atripla coformulation), according to 2-year data from the ECHO and THRIVE trials published in the April 11 online edition of Clinical Infectious Diseases.

Studies have shown that people with HIV have higher rates of cardiovascular disease compared with the general population. Whether this is due to HIV infection itself, related inflammation or metabolic changes, antiretroviral drug toxicities, or other factors is not yet fully understood. Antiretrovirals that have less detrimental effect on blood fat levels may help reduce heart disease risk.

Pablo Tebas from the University of Pennsylvania and colleagues looked at changes in blood lipid levels and body fat at 96 weeks in the ECHO and THRIVE trials. These were similar multinational Phase 3 studies comparing non-nucleoside reverse transcriptase inhibitors (NNRTIs) in a combined total of 1370 treatment-naive people with HIV.

Participants in both studies were randomly assigned to receive 25 mg rilpivirine or 600 mg efavirenz, both once-daily. All ECHO participants also received tenofovir plus emtricitabine (the drugs in Truvada) as a NRTI backbone, while THRIVE participants could use tenofovir/emtricitabine, zidovudine/lamivudine (Combivir), or abacavir/lamivudine (Epzicom). Primary 48-week results from ECHO and THRIVE were published in the July 16, 2011, issue of The Lancet, showing that both drugs had similar efficacy.

In the present analysis the researchers analyzed blood levels of total cholesterol, low-density lipoprotein (LDL or "bad") cholesterol, high-density lipoprotein (HDL or "good") cholesterol, and triglycerides. They also determined the proportion of patients falling above or below National Cholesterol Education Program (NCEP) cut-offs for increased cardiovascular risk, and measured body fat changes using dual-energy X-ray absorptiometry (DEXA).


  • Rilpivirine produced minimal changes in total cholesterol, LDL, HDL, and triglycerides.
  • Compared with rilpivirine, efavirenz was associated with significantly larger lipid increases at 96 weeks.
  • Total cholesterol-to-HDL ratios were similar in the rilpivirine and efavirenz arms.
  • NRTI backbone drugs also played a role:

o   Among patients taking rilpivirine, all cholesterol levels rose with zidovudine/lamivudine and abacavir/lamivudine, while HDL increased and total cholesterol and LDL remained stable with tenofovir/emtricitabine.

o   Among patients taking efavirenz, lipid levels increased with all NRTI combinations.

  • Significantly fewer rilpivirine recipients had total cholesterol, LDL, and triglycerides above NCEP cardiovascular risk cut-offs.
  • Participants taking rilpivirine were also significantly less likely to have HDL levels below the NCEP cut-off.
  • Adverse events related to abnormal lipid levels were less common in the rilpivirine arms.
  • A similar proportion of patients had at least a 10% decrease in limb fat (16% with rilpivirine vs 17% with efavirenz).
  • Similar proportions also experienced limb fat increases (12% vs 11%, respectively).
  • Overall, patients taking zidovudine/lamivudine with either NNRTI lost limb fat, while those taking tenofovir/emtricitabine gained limb fat.

"Over 96 weeks, rilpivirine-based therapy was associated with lower increases in lipid parameters and fewer dyslipidemia adverse events than efavirenz-based treatment," the study authors concluded. "Body fat distribution changes were similar between treatments."



P Tebas, M Sension, J Arribas, et al. Analysis of Lipid Levels and Changes in Body Fat Distribution in Treatment-Naive, HIV-1-Infected Adults Treated with Rilpivirine or Efavirenz Over 96 Weeks in the ECHO and THRIVE Trials. Clinical Infectious Diseases April 11, 2014 (Epub ahead of print).