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Week 96 efficacy and safety of rilpivirine in treatment-naive, HIV-1 patients in two Phase III randomized trials

Cohen, Calvin J.a; Molina, Jean-Michelb; Cassetti, Isabelc; Chetchotisakd, Ploenchand; Lazzarin, Adrianoe; Orkin, Chloef; Rhame, Frankg; Stellbrink, Hans-Jürgenh; Li, Taishengi; Crauwels, Hertaj; Rimsky, Laurencej; Vanveggel, Simonj; Williams, Peterj; Boven, Katiakon behalf of the ECHO, THRIVE study groups

doi: 10.1097/QAD.0b013e32835cee6e
Clinical Science

Background: In the week 48 primary analysis of ECHO and THRIVE, rilpivirine demonstrated noninferior efficacy and more favourable tolerability versus efavirenz in treatment-naive, HIV-1-infected adults. Pooled 96-week results are presented.

Methods: Patients (N = 1368) received rilpivirine 25 mg once-daily (q.d.) or efavirenz 600 mg q.d., with two background nucleoside/nucleotide reverse transcriptase inhibitors, in two randomized, double-blind, double-dummy Phase III trials.

Results: At week 96, response rate (% confirmed viral load <50 copies/ml; intent-to-treat, time-to-loss-of-virologic response) was 78% in both groups. Responses were similar for both treatments by background regimen, sex, race, and in patients with more than 95% adherence (M-MASRI) or baseline viral load 100 000 copies/ml or less. Responses were lower and virologic failure higher for rilpivirine versus efavirenz in patients with 95% or less adherence or baseline viral load more than 100 000 copies/ml. Beyond week 48, the incidence of virologic failure was comparable (3 versus 2%) between treatment groups, rilpivirine resistance-associated mutations were consistent with those observed in year 1, there were few adverse events in both groups and no new safety concerns. Over 96 weeks, discontinuations due to adverse events (4 versus 9%), treatment-related grade 2–4 adverse events (17 versus 33%), rash (4 versus 15%), dizziness (8 versus 27%) and abnormal dreams/nightmares (8 versus 13%), and grade 2–4 lipid abnormalities were lower with rilpivirine than efavirenz. Only 2 and 4% of patients in the rilpivirine and efavirenz treatment groups, respectively, reported at least possibly treatment-related grade 2–4 adverse events during the second year of treatment.

Conclusions: Rilpivirine 25 mg q.d. and efavirenz 600 mg q.d. had comparable responses at week 96. Rilpivirine had more virologic failures but improved tolerability versus efavirenz. The majority of virologic failures occurred in the first 48 weeks.

aCommunity Research Initiative of New England, Boston, Massachusetts, USA

bDepartment of Infectious Diseases, Saint-Louis Hospital, University of Paris Diderot, Paris 7, Paris, France

cHelios Salud, Buenos Aires, Argentina

dFaculty of Medicine, Khon Kaen University, Khon Kaen, Thailand

eVita-Salute,San Raffaele University, Milan, Italy

fBarts and the London NHS Trust, London, UK

gAbbott Northwestern Hospital, Minneapolis, Minnesota, USA

hICH Study Center, Hamburg, Germany

iDepartment of Infectious Diseases, Peking Union Medical College Hospital, Beijing, China

jJanssen Infectious Diseases BVBA, Beerse, Belgium

kJanssen Research and Development, LLC, Titusville, New Jersey, USA.

Correspondence to Calvin J. Cohen, Community Research Initiative of New England, Boston, MA 02215, USA. Tel: +1 617 502 1740; fax: +1 617 502 1701; e-mail: ccohen@crine.org

Received 15 June, 2012

Revised 16 November, 2012

Accepted 22 November, 2012

Meetings at which parts of the data have been presented: Cohen CJ, Molina JM, Cassetti I, et al. Pooled Week 96 efficacy, resistance and safety results from the double-blind randomised, Phase III trials comparing rilpivirine (RPV,TMC278) versus efavirenz (EFV) in treatment-naïve, HIV-1-infected adults. 6th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention, Rome, Italy 17–20 July 2011. Poster TULBPE032. (Also presented as an encore at EACS 2011 and BHIVA 2012). Rimsky L, Van Eygen V, Vingerhoets J, et al. Week 96 resistance analysis of the rilpivirine (RPV, TMC278) Phase III trials in treatment-naïve HIV-infected adults. 19th Conference on Retroviruses and Opportunistic Infections, Seattle, WA, USA, March 5–8, 2012. Poster 708. Cohen C, Molina J-M, Jayaweera D, et al. Relationship between combination of baseline viral load and CD4 cell count, and Week 48 or 96 responses to rilpivirine (RPV) or efavirenz (EFV) in treatment-naïve HIV-1-infected adults: pooled analysis from the Phase III ECHO and THRIVE trials. 19th Conference on Retroviruses and Opportunistic Infections, Seattle, WA, USA, March 5–8, 2012. Poster 626. Bloch M, Crane LR, Reynes J, et al. Safety and efficacy outcomes by N(t)RTI background regimen over 96 weeks in treatment-naïve HIV-1-infected patients treated with rilpivirine or efavirenz in the Phase III ECHO and THRIVE trials. 49th Annual Meeting of the Infectious Diseases Society of America and the HIV Medicine Association, Boston, MA, USA, October 20–23 2011. Poster 408. Martorell C, Mayer CA, Ribera E, et al. Week 96 safety and efficacy by gender and race subgroups in treatment-naïve HIV-1-infected patients in the Phase III ECHO and THRIVE trials. 49th Annual Meeting of the Infectious Diseases Society of America and the HIV Medicine Association, Boston, MA, USA, October 20–23 2011. Poster 404.

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