Rilpivirine (Edurant)

Detailed information

Rilpivirine (Edurant) is a second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI), developed by Janssen (formerly Tibotec). Rilpivirine was submitted for licensing in the United States in November 2010 and received approval for use as first-line treatment in May 2011. European marketing approval followed in November 2011.

Rilpivirine (Edurant) is approved for HIV treatment in people with viral loads below 100,000 copies/ml.

Rilpivirine is also available in several combination tablets:

  • As a once-daily tablet (Eviplera) with Gilead’s drugs tenofovir disoproxil fumarate (TDF) and emtricitabine, which received marketing approval in the EU in November 2011. This combination tablet is marketed as Complera in the US.
  • As a once-daily tablet (Odefsey) in combination with tenofovir alafenamide (TAF) and emtricitabine, approved in the EU in 2016
  • As a once-daily tablet in combination with the integrase inhibitor dolutegravir, called Juluca, approved in the EU in 2018

Rilpivirine is also available as a long-acting injectable treatment (Rekambys) in combination with cabotegravir (Vocabria), approved in the EU in 2020.


Rilpivirine was approved based on the findings of two international phase III studies, ECHO and THRIVE, each of which compared rilpivirine 25mg once daily to efavirenz 600mg once daily, in combination with two nucleoside analogues, in treatment-naive individuals. (Cohen)

The ECHO study randomised 690 patients, and all received a nucleoside analogue backbone of TDF and emtricitabine. THRIVE randomised 678 patients, with the nucleoside backbone chosen by the patient’s doctor: around 60% of participants received TDF/emtricitabine, 30% received zidovudine/lamivudine and 10% received abacavir/lamivudine.

Participants had relatively low CD4 counts (a median of around 250), and high viral load (median 5 log, or 100,000 copies/ml). After 48 weeks of treatment the proportions with viral load below 50 copies/ml were almost identical (84.3% in the rilpivirine arm, 82.3% in the efavirenz arm), demonstrating non-inferiority.

Virological failures (defined as two viral loads above 50 copies/ml even if viral load was suppressed again at week 48) were more frequent in the rilpivirine arm (9 vs 4.8%), and this difference was largely driven by the higher failure rate in the ECHO study (11 vs 4.4%). The statistical significance of this difference was not reported, but the difference did not vary according to nucleoside backbone, nor by baseline viral load.

Pooled analysis of the studies showed that among people with baseline viral loads above 100,000 copies/ml, virological failure occurred significantly more often in people randomised to rilpivirine. (Molina)

A subsequent 96-week phase 3b study showed that treatment with a fixed-dose combination of rilpivirine, TDF and emtricitabine resulted in superior viral suppression in previously untreated people with viral loads below 100,000 copies/ml when compared to a fixed-dose combination of efavirenz, TDF and emtricitabine. Discontinuations due to adverse events were significantly less common in the rilpivirine arm. Based on these findings, the fixed-dose combination Eviplera was approved in 2011. (Van Lunzen)


viral load

Measurement of the amount of virus in a blood sample, reported as number of HIV RNA copies per milliliter of blood plasma. Viral load is an important indicator of HIV progression and of how well treatment is working. 


fixed-dose combination (FDC)

Two or more drugs contained in a single dosage form, such as a capsule or tablet. By reducing the number of pills a person must take each day, fixed-dose combination drugs may help improve adherence.


A drug-resistant HIV strain is one which is less susceptible to the effects of one or more anti-HIV drugs because of an accumulation of HIV mutations in its genotype. Resistance can be the result of a poor adherence to treatment or of transmission of an already resistant virus.


A precursor to a building block of DNA or RNA. Nucleosides must be chemically changed into nucleotides before they can be used to make DNA or RNA. 


In a clinical trial, a group or subgroup of participants that receives a specific intervention/treatment, or no intervention, according to the trial's protocol. 

Two phase 3b studies that evaluated a switch from Eviplera to a fixed-dose combination containing TAF, rilpivirine and emtricitabine showed equivalent rates of viral suppression after 96 weeks and significant improvements in bone turnover and kidney tubule markers. Based on these findings, the fixed-dose combination Odefsey was approved in 2011. (Hagins)

Post-approval studies also showed that people with suppressed viral load could switch to rilpivirine and maintain viral suppression, and that switching from efavirenz to rilpivirine reduced central nervous system side effects. (Cohen 2011) (Nelson)

The PROBE-2 study tested darunavir, boosted by cobicistat, and rilpivirine in people with suppressed viral load on a three-drug regimen. After 24 weeks, people who were assigned to switch to the two-drug regimen had a similar rate of viral suppression to those who remained on the three-drug regimen. Rilpivirine and darunavir/cobicistat was recommended as a new switch option in the 2019 EACS European treatment guidelines. (Maggiolo)

For further information about the effectiveness of the combination of dolutegravir and rilpivirine, see Juluca.

For further information about the injectable formulation of rilpivirine, see Cabotegravir (Vocabria) & rilpivirine (Rekambys) injections.

Taking it

Any oral fixed-dose combination containing rilpivirine (Eviplera; Odefsey; Juluca) must be taken with a meal so that rilpivirine is fully absorbed.

Adherence to rilpivirine must be very high (missing no more than one dose a month) to avoid treatment failure and drug resistance. Rilpivirine may not be suitable for people who are likely to face problems with taking medication each day.

The standard dose of rilpivirine is 25mg once a day. Edurant is a white tablet. The dose should be increased to 50mg (two tablets once a day) if taken with rifabutin.

Eviplera contains 25mg of rilpivirine, 245mg of TDF and 200mg of emtricitabine. Eviplera is a green oval tablet.

Odefsey contains 25mg of rilpivirine, 25mg of TAF and 200mg of emtricitabine. Odefsey is a grey oval tablet.

Side effects

The common side effects of rilpivirine are (most common in bold):

  • insomnia (difficulty sleeping), abnormal dreams, sleep disorders, tiredness, drowsiness
  • nausea, vomiting, stomach pain or discomfort, reduced appetite, dry mouth
  • headache, dizziness, depression, low mood
  • rash
  • raised cholesterol, liver enzymes or pancreatic amylase, reduced white or red blood cell count, low platelet count, raised triglyceride or lipase levels.

Weight gain has been observed in people with HIV after starting antiretroviral treatment.

People taking rilpivirine gained more weight than those taking efavirenz in phase 3 trials, but the amount of weight gained was modest (approximately 2.5kg). (Sax) A retrospective study of Italians who switched from TDF to TAF while continuing to take rilpivirine found that those who switched to TAF gained significantly more weight. Women, people with low CD4 counts and people with a higher body mass index were at greater risk of weight gain. (Taramasso)

Drug interactions

You should not take rilpivirine with:

  • carbamazepine
  • dexamethasone
  • esomeprazole
  • lansoprazole
  • omeprazole
  • oxcarbazepine
  • pantoprazole
  • phenobarbital
  • phenytoin
  • rabeprazole
  • rifampicin
  • rifapentine
  • St John's wort.

It’s not recommended that rilpivirine be used in combination with other NNRTIs.

Some drugs can interact with rilpivirine and change blood levels of one or both drugs, so dose adjustments may be needed. These drugs include:

  • cimetidine
  • clarithromycin
  • dabigatran etexilate
  • erythromycin
  • famotidine
  • methadone
  • nizatidine
  • ranitidine
  • rifabutin.

Medicines that affect stomach acidity can block the way rilpivirine is absorbed. Indigestion remedies called H2-blockers (such as ranitidine, Zantac) should be taken at least 12 hours before or at least four hours after taking rilpivirine. If taking other indigestion remedies (such as Rennies or Gaviscon) or calcium supplements, they should be taken at least two hours before or at least four hours after taking rilpivirine as they can prevent it being absorbed properly.


Patients taking rilpivirine who experienced virological failure tended to develop the E138K mutation that causes resistance to the second-line NNRTI etravirine. Half of those who experienced treatment failure while taking rilpivirine developed resistance to the drug, and of them, 90% developed resistance to etravirine too.


The British HIV Association (BHIVA) lists rilpivirine (in combination with other medications) as an option that may be considered for women who start HIV treatment in pregnancy, depending on their individual circumstances.


Rilpivirine is approved for use in children aged 12 years and over.


Cohen C et al. Week 96 efficacy and safety of rilpivirine in treatment-naive, HIV-1 patients in two Phase III randomized trials. AIDS, 276: 939-950, 2013.

Molina J-H et al. Week 96 analysis of rilpivirine or efavirenz in HIV-1-infected patients with baseline viral load ≤ 100 000 copies/mL in the pooled ECHO and THRIVE phase 3, randomized, double-blind trials. HIV Medicine, 15: 57-62, 2014.

Van Lunzen J et al. Rilpivirine vs. efavirenz-based single-tablet regimens in treatment-naive adults: week 96 efficacy and safety from a randomized phase 3b study. AIDS, 30: 251-9, 2016.

Hagins D et al. Switching to coformulated rilpivirine (RPV), emtricitabine (FTC) and tenofovir alafenamide from either RPV, FTC and tenofovir disoproxil fumarate (TDF) or efavirenz, FTC and TDF: 96-week results from two randomized clinical trials. HIV Medicine, 19: 724-733, 2018.

Cohen C et al. Switching from efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) single tablet regimen (STR) to emtricitabine/rilpivirine/tenofovir disoproxil fumarate (FTC/RPV/TDF) STR in virologically suppressed, HIV-1 infected subjects. 13th European AIDS Conference, LBPS10/4, Belgrade, 2011.

Nelson M et al. Multicentre Open-label study of switching from Atripla to Eviplera for possible efavirenz associated CNS toxicity. 53rd Interscience Conference on Antimicrobial Agents and Chemotherapy, Denver, abstract H-672b, 2013.

Maggiolo F et al. Rilpivirine plus cobicistat-boosted darunavir as a two-drug switch regimen in HIV-infected, virologically suppressed subjects on steady standard three-drug therapy: a randomized, controlled, non-inferiority trial (PROBE 2). Journal of Antimicrobial Chemotherapy, 75: 1332-37, 2020.

Sax P et al. Weight gain following initiation of antiretroviral therapy: risk factors in randomized comparative clinical trials. Clinical Infectious Diseases, 71: 1379-89, 2019.

Taramasso L et al. The switch from tenofovir disoproxil fumarate to tenofovir alafenamide determines weight gain in patients on rilpivirine-based regimens. AIDS, 34: 877-881, 2020.

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