Rilpivirine, also called TMC278, is an anti-HIV drug chemically related to the non-nuke family of drugs, which includes efavirenz (Sustiva and in Atripla), nevirapine (Viramune) and etravirine (Intelence).

Rilpivirine is being tested as part of combination therapy for the initial therapy of HIV infection against efavirenz-based combinations. Unlike efavirenz, rilpivirine does not appear to cause birth defects in animal experiments. Rilpivirine remains in the blood for prolonged periods, with a half-life of 45 hours. This means that it can be taken once daily. At doses of 25 mg per day, in short and small studies rilpivirine has similar efficacy as efavirenz but is better tolerated.

Now researchers have combined (or pooled) the results of two large comparative trials of rilpivirine vs. efavirenz -- Echo and Thrive. Analysis of these two studies suggests that, overall, rilpivirine-based regimens are roughly equivalent to efavirenz-based regimens. However, results from each trial were slightly different and worth further scrutiny.

Study Details

In the Echo trial, 690 HIV-positive people who had not previously used anti-HIV therapy were randomly assigned to receive one of the following regimens:

  • rilpivirine 25 mg once daily with Truvada (tenofovir + FTC) also once daily
  • efavirenz 600 mg once daily with Truvada

In the Thrive trial, the overall design was similar except that doctors were allowed to use any of the following nuke combinations with either rilpivirine or efavirenz:

  • Truvada
  • AZT + 3TC in one pill (Combivir)
  • abacavir + 3TC in one pill (Kivexa)

The average profile of participants when they entered the Echo and Thrive studies were as follows:

  • 25% females, 75% males
  • age -- 36 years
  • CD4+ count -- 250 cells
  • viral load -- 100,000 copies/ml
  • 8% were co-infected with hepatitis B or C virus

These trials lasted two years but so far only the results from the first year have been released.

Results -- Suppression of HIV

When the results of Echo and Thrive were combined, the proportion of participants with a viral load less than 50 copies/ml at 48 weeks was as follows:

  • rilpivirine -- 84%
  • efavirenz -- 82%

This difference was not statistically significant

CD4+ cell counts increased in both groups as follows:

  • rilpivirine -- 192 extra CD4+ cells
  • efavirenz -- 176 extra CD4+ cells

Again, this difference was not statistically significant.

In examining the results of the studies individually, rilpivirine was found to be roughly equivalent to efavirenz in anti-HIV activity. The technical statistical term for this is non-inferior.

In the combined analysis, 9% of rilpivirine users developed virologic failure compared to 5% of efavirenz users. This difference was driven by results from the Echo study, where differences in virologic failure were as follows:

  • rilpivirine -- 11% developed virologic failure
  • efavirenz -- 4% developed virologic failure

This occurred despite 83% of participants who received rilpivirine or efavirenz achieving a viral load less than 50 copies/ml. Clues to possibly explain the differences between the two drugs and the two trials may be found below.

In assessing differences in outcomes, the proportion of participants in Echo whose baseline (starting) viral load was greater than 100,000 copies/ml and who later achieved a viral load less than 50 copies/ml was as follows:

  • rilpivirine -- 76% achieved a viral load less than 50 copies/ml
  • efavirenz -- 82% achieved a viral load less than 50 copies/ml

Yet this difference was not statistically significant.

In Thrive, the results in participants with high baseline viral loads (more than 100,000) were as follows:

  • rilpivirine -- 79% achieved a viral load less than 50 copies/ml
  • efavirenz -- 80% achieved a viral load less than 50 copies/ml

This difference was not statistically significant. Nonetheless, the reason(s) for the slightly different results of Echo and Thrive are not clear at this time.

Results -- Side Effects

The proportion of participants who had side effects judged as moderate to life-threatening and possibly related to exposure to treatment were as follows:

  • rilpivirine -- 16%
  • efavirenz -- 31%

This difference was not statistically significant.

Common differences in side effects highlighted by the Echo and Thrive investigators were as follows:

Any Neurological Side Effect:

  • rilpivirine -- 17%
  • efavirenz -- 38%


  • rilpivirine -- 8%
  • efavirenz -- 26%

Any Psychiatric Side Effects:

  • rilpivirine -- 15%
  • efavirenz -- 23%

Abnormal Dreams or Nightmares:

  • rilpivirine -- 8%
  • efavirenz -- 13%


  • rilpivirine -- 3%
  • efavirenz -- 14%

These differences were all statistically significant.

When researchers assessed lab tests of blood samples for signals of toxicity they found these differences between the two drugs:

Any Severe or Life-Threatening Value in All Lab Tests:

  • rilpivirine -- 11%
  • efavirenz -- 18%

This difference was statistically significant.

Any Severe or Life-Threatening Value in the Following Lab Tests:

Liver enzyme ALT:

  • rilpivirine -- 2%
  • efavirenz -- 3%

Fasting Levels of LDL-Cholesterol:

  • rilpivirine -- 1%
  • efavirenz -- 3%

Fasting Total Cholesterol:

  • rilpivirine -- 0.1%
  • efavirenz -- 3%

All of these differences were statistically significant.

Overall, rilpivirine appears to be as effective as efavirenz. Rilpivirine also appears to be better tolerated, with fewer rash, lipid and neurologic problems than efavirenz.


  1. Cohen C, Molina J-M, Cahn P, et al. Pooled week 48 efficacy and safety results from ECHO and THRIVE, two double-blind randomized Phase III trials comparing TMC278 versus efavirenz in treatment-naive HIV-1-infected patients. In: Program and abstracts of the 18th International Conference on AIDS, 18-23 July 2010, Vienna, Austria. Abstract THLBB206.