Observational cohort study of rilpivirine (RPV) utilization in Europe
Authors: Cozzi-Lepri Alessandro , Peters Lars , Pelchen-Matthews Annegret , Neesgaard Bastian , De Wit Stephane , Johansen Isik Somuncu , Edwards Simon , Stephan Christoph , Adamis Georgios , Staub Therese , Zagalo Alexandra , Domingo Pere , Elbirt Daniel , Kusejko Katharina , Brännström Johanna , Paduta Dzmitry , Trofimova Tatyana , Szlavik Janos , Zilmer Kai , Losso Marcello , Van Eygen Veerle , Pai Helen , Lundgren Jens , Mocroft Amanda ,   for the EuroSIDA Study Group, Harxhi A. , Losso M. , Kundro M. , Schmied B. , Karpov I. , Vassilenko A. , Paduto D. , Mitsura V. M. , Clumeck N. , De Wit S. , Delforge M. , Hadziosmanovic V. , Begovac J. , Machala L. , Jilich D. , Gerstoft J. , Pedersen C. , Sedlacek D. , Kronborg G. , Benfield T. , Johansen I. S. , Ostergaard L. , Wiese L. , Moller N. F. , Nielsen L. N. , Zilmer K. , Smidt Jelena , Aho I. , Viard J. P. , Girard P. M. , Pradier C. , Fontas E. , Duvivier C. , Rockstroh J. , Degen O. , Hoffmann C. , Stellbrink H. J. , Stefan C. , Bogner J. , Fätkenheuer G. , Chkhartishvili N. , Sambatakou H. , Adamis G. , Paissios N. , Uzdaviniene V. , Staub T. , Dragas S. , Reiss P. , Trajanovska J. , Reikvam D. H. , Maeland A. , Bruun J. , Knysz B. , Szetela B. , Inglot M. , Bakowska E. , Flisiak R. , Grzeszczuk A. , Parczewski M. , Maciejewska K. , Aksak-Was B. , Beniowski M. , Mularska E. , Jablonowska E. , Kamerys J. , Wojcik K. , Mozer-Lisewska I. , Rozplochowski B. , Zagalo A. , Radoi R. , Oprea C. , Yakovlev A. , Trofimora T. , Khromova I. , Kuzovatova E. , Borodulina E. , Vdoushkina E. , Ranin J. , Tomazic J. , Miro J. M. , Laguno M. , Martinez E. , Garcia F. , Blanco J. L. , Martinez-Rebollar M. , Mallolas J. , Callau P. , Rojas J. , Moreno S. , del Campo S. , Jou A. , Paredes R. , Puig J. , Llibre J. M. , Santos J. R. , Domingo P. , Gutierrez M. , Mateo G. M. , Sambeat A. , Laporte J. M. , Svedhem V. , Thalme A. , Sonnerborg A. , Flamholc L. , Kusejko K. , Weber R. , Calmy A. , Furrer H. , Battegay M. , Schmid P. , Kuznetsova A. , Mikhalik J. , Sluzhynska M. , Milinkovic A. , Johnson A. M. , Simons E. , Edwards S. , Phillips A. M. , Johnson A. , Mocroft A. , Orkin C. , Winston A. , Clarke A. , Leen C. 
Published: August 2022

Abstract
Introduction
Data on safety and effectiveness of RPV from the real-world setting as well as comparisons with other NNRTIs such as efavirenz (EFV) remain scarce.

Methods
Participants of EuroSIDA were included if they had started a RPV- or an EFV-containing regimen over November 2011-December 2017. Statistical testing was conducted using non-parametric Mann–Whitney U test and Chi-square test. A logistic regression model was used to compare participants’ characteristics by treatment group. Kaplan–Meier analysis was used to estimate the cumulative risk of virological failure (VF, two consecutive values > 50 copies/mL).

Results
1,355 PLWH who started a RPV-based regimen (11% ART-naïve), as well as 333 initiating an EFV-containing regimen were included. Participants who started RPV differed from those starting EFV for demographics (age, geographical region) and immune-virological profiles (CD4 count, HIV RNA). The cumulative risk of VF for the RPV-based group was 4.5% (95% CI 3.3–5.7%) by 2 years from starting treatment (71 total VF events). Five out of 15 (33%) with resistance data available in the RPV group showed resistance-associated mutations vs. 3/13 (23%) among those in the EFV group. Discontinuations due to intolerance/toxicity were reported for 73 (15%) of RPV- vs. 45 (30%) of EFV-treated participants (p = 0.0001). The main difference was for toxicity of central nervous system (CNS, 3% vs. 22%, p < 0.001).

Conclusion
Our estimates of VF > 50 copies/mL and resistance in participants treated with RPV were similar to those reported by other studies. RPV safety profile was favourable with less frequent discontinuation due to toxicity than EFV (especially for CNS).