Skip to main content
Article thumbnail
Location of Repository

Safety, efficacy, and pharmacokinetics of rilpivirine: systematic review with an emphasis on resource-limited settings.

By Nathan Ford, Janice Lee, Isabelle Andrieux-Meyer and Alexandra Calmy


The vast majority of people living with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome reside in the developing world, in settings characterized by limited health budgets, critical shortages of doctors, limited laboratory monitoring, a substantial burden of HIV in children, and high rates of coinfection, in particular tuberculosis. Therefore, the extent to which new antiretrovirals will contribute to improvements in the management of HIV globally will depend to a large extent on their affordability, ease of use, low toxicity profile, availability as pediatric formulations, and compatibility with tuberculosis and other common drugs. We undertook a systematic review of the available evidence regarding drug interactions, and the efficacy and safety of rilpivirine (also known as TMC-278), and assessed our findings in view of the needs and constraints of resource-limited settings. The main pharmacokinetic interactions relevant to HIV management reported to date include reduced bioavailability of rilpivirine when coadministered with rifampicin, rifabutin or acid suppressing agents, and reduced bioavailability of ketoconazole. Potential recommendations for dose adjustment to compensate for these interactions have not been elaborated. Trials comparing rilpivirine and efavirenz found similar outcomes up to 96 weeks in intent-to-treat analysis; failure of rilpivirine was mainly virological, whereas failure among those exposed to efavirenz was mainly related to the occurrence of adverse events. Around half of the patients who fail rilpivirine develop non-nucleoside reverse transcriptase inhibitor resistance mutations. The incidence of Grade 2-4 events was lower for rilpivirine compared with efavirenz. Grade 3-4 adverse events potentially related to the drugs were infrequent and statistically similar for both drugs. No dose-response relationship was observed for efficacy or safety, and the lowest dose (25 mg) was selected for further clinical development. The potential low cost and dose of the active pharmaceutical ingredient means that rilpivirine can potentially be manufactured at a low price. Moreover, its long half-life suggests the potential for monthly dosing via nonoral routes, with promising early results from studies of a long-acting injectable formulation. These characteristics make rilpivirine an attractive drug for resource-limited settings. Future research should assess the potential to improve robustness and assess the clinical significance of interaction with antituberculosis drugs

Publisher: DovePress
Year: 2011
DOI identifier: 10.2147/HIV.S14559
OAI identifier:
Provided by: MSF Field Research

Suggested articles


  1. (2009). Absence of a teratogenic potential from a novel next generation
  2. (2006). Adherence to HAART: A systematic review of developed and developing nation patient-reported barriers and facilitators. PLoS Med.
  3. Antiretroviral Therapy Cohort Collaboration. Life expectancy of individuals on combination antiretroviral therapy in high-income countries: A collaborative analysis of 14 cohort studies.
  4. (2010). Bioequivalence of the co-formulation of emtricitabine/rilpivirine/tenofovir DF.
  5. (2010). Campaign for Essential Medicines. Untangling the Web of Antiretroviral Price Reduction. 13th ed.
  6. (2010). Characterization of the resistance profile of TMC278:
  7. Development of a long-acting injectable formulation with nanoparticles of rilpivirine (TMC278) for HIV treatment.
  8. (2005). Effect of food and multiple dose pharmacokinetics of TMC278 as an oral tablet formulation.
  9. Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women.
  10. Efficacy and safety of TMC278 in antiretroviral-naive HIV-1 patients: Week 96 results of a phase IIb randomized trial.
  11. Ethical allocation of preexposure HIV prophylaxis.
  12. Examining the production costs of antiretroviral drugs.
  13. (2010). for the TASO-CAN group. Life expectancy of individuals on combination antiretroviral therapy in Uganda: a cohort analysis of more than 23,000 patients.
  14. In search of a novel anti-HIV drug: Multidisciplinary coordination in the discovery of 4-[[4-[[4-[(1E)-2-cyanoethenyl]-2,6-dimethylphenyl]amino]-2- pyrimidinyl]amino]benzonitrile (R278474, rilpivirine).
  15. (2009). New antiretroviral drugs: A review of the efficacy, safety, pharmacokinetics, and resistance profile of tipranavir, darunavir, etravirine, rilpivirine, maraviroc, and raltegravir. Expert Opin Pharmacother.
  16. Nonnucleoside reverse transcriptase inhibitor resistance and the role of the secondgeneration agents.
  17. (2009). Organization. Towards universal access: Scaling up priority HIV/AIDS interventions in the health sector. Progress report.
  18. (2011). Organization. Updated List of Missing Drug Formulations for HIV Treatment to be Reviewed by the
  19. (2005). Pharmacokinetic interaction between the novel non-nucleoside reverse transcriptase inhibitor (NNRTI) TMC278 and tenofovir fumarate (TDF) in healthy volunteers.
  20. (2010). Pharmacokinetic interaction study between TMC278, a next-generation NNRTI, and methadone. Abstract WEPE0089, presented at the XVIII International AIDS Conference,
  21. (2009). Pharmacokinetic interaction study between TMC278, an NNRTI, and the contraceptives norethindrone plus ethinylestradiol. Presented at the
  22. (2010). Pharmacokinetics and disposition of rilpivirine (TMC278) nanosuspension as a long-acting injectable antiretroviral formulation. Antimicrob Agents Chemother.
  23. (2010). Pooled week 48 safety and efficacy results from the
  24. Powder for reconstitution of the anti-HIV-1 drug TMC278 – formulation development, stability and animal studies.
  25. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men.
  26. (2010). Preliminary analysis of biomedical data from the Phase II clinical safety trial of tenofovir disoproxil fumarate (TDF) for HIV-1 pre-exposure prophylaxis (PrEP) among US men who have sex with men (MSM).
  27. (2010). Relative bioavailability of a concept paediatric formulation of TMC278, an investigational NNRTI.
  28. (2011). Rilpivirine: A new addition to the anti-HIV-1 armamentarium. Drugs Today (Barc).
  29. (2009). Rilpivirine: A novel non-nucleoside reverse transcriptase inhibitor. Expert Opin Investig Drugs.
  30. Safety of efavirenz in firsttrimester of pregnancy: A systematic review and meta-analysis of outcomes from observational cohorts.
  31. Short-term antiviral activity of TMC278 – a novel NNRTI – in treatment-naive HIV-1-infected subjects.
  32. Short-term randomized proofof- principle trial of TMC278 in patients with HIV type-1 who have previously failed antiretroviral therapy. Antiviral Ther.
  33. (2008). The effect of different types of food on the bioavailability of TMC278, an investigational NNRTI.
  34. (2006). The effects of CYP3A4 modulation on the pharmacokinetics of TMC278, an investigational non-nucleoside reverse transcriptase inhibitor (NNRTI).
  35. (2007). The pharmacokinetic (PK) interaction between famotidine and TMC278, a next generation non-nucleoside reverse transcriptase inhibitor (NNRTI), in HIV-negative volunteers.
  36. (2008). The pharmacokinetic (PK) interaction between rifabutin and TMC278, an investigational non-nucleoside reverse transcriptase inhibitor (NNRTI).
  37. (2007). The pharmacokinetic interaction between atorvastatin and TMC278, a next- generation non-nucleoside reverse transcriptase inhibitor, in HIV-negative volunteers.
  38. (2006). The pharmacokinetic interaction between ketoconazole and TMC278, an investigational non-nucleoside reverse transcriptase inhibitor (NNRTI), in healthy HIV-negative subjects.
  39. (2007). The pharmacokinetic interaction between TMC 278, a next generation NNRTI, and once-daily darunavir/ritonavir
  40. (2008). TMC278 (rilpivirine), a next-generation NNRTI, demonstrates long-term efficacy and tolerability in ARV-naïve patients: 96-week results of study
  41. (2009). TMC278 25 mg qd has no effect on corrected QT interval in a study in HIV-negative volunteers.
  42. (2008). TMC278 long acting – a parenteral nanosuspension formulation that provides sustained clinically relevant plasma concentrations in HIV-negative volunteers.
  43. (2005). TMC278, a new potent NNRTI, with an increased barrier to resistance and favourable pharmacokinetic profile.
  44. (2009). TMC278, a nextgeneration NNRTI, does not alter the pharmacokinetics of sildenafil.
  45. Tuberculosis as part of the natural history of HIV infection in developing countries. Clin Infect Dis.

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.