Switching to Coformulated Rilpivirine/Emtricitabine/Tenofovir in Virologically Suppressed Patients: Data From a Multicenter Cohort.

In clinical trials, a first-line combination antiretroviral therapy (cART) including rilpivirine has demonstrated noninferior efficacy when compared with efavirenz, with a lower incidence of adverse events and better tolerability, although the ability to induce and maintain virological benefit was reduced in patients with low CD4+ cell count or high viral load. Because of the availability of rilpivirine coformulated with tenofovir/ emtricitabine (RPV/FTC/TDF) in a single-tablet regimen (STR) and to a favorable tolerability profile, RPV/FTC/ TDF is also expected to be a valuable option for treatment simplification in treatment-experienced patients. In this setting, an improvement of general satisfaction in patients who simplified from nevirapine plus tenofovir/emtricitabine and a resolution of central nervous system side effects after switching from efavirenz/tenofovir/emtricitabine to RPV/FTC/TDF were reported. However, few data are available on efficacy and safety of treatment switch to rilpivirinebased regimens in routine clinical practice and most studies included only a few number of patients. Thus, the aim of our study was to describe the efficacy and safety of treatment simplification to RPV/ FTC/TDF in routine clinical practice in a large multicenter cohort of treatmentexperienced patients. From the database of 6 Italian reference centers for HIV infection, all patients on cART with HIV-RNA ,50 copies per milliliter switching to RPV/FTC/TDF were retrospectively selected. The patients were followed from RPV/FTC/TDF initiation (baseline) to regimen discontinuation or to the last available visit. Demographic, clinical, viroimmunological, and laboratory data were collected from both the database and chart review. Reasons for regimen switch/discontinuation, as reported by the caring physician and aggregated according to a predefined list, were collected. Virological failure was defined as the first of 2 consecutive detectable HIV viral loads (.50 copies/mL) during follow-up. Predictors of virological failure or RPV/FTC/TDF discontinuation were assessed using Cox proportional hazard regression; variables showing a significant association with the outcome at univariate analysis were then evaluated in a multivariable model. The evolution of main laboratory markers after treatment simplification was analyzed with Student t test for paired samples. Overall, 508 virologically suppressed patients (72% males, median age: 50 years, 23.6% HCV coinfected, 17.5% with past AIDS-defining events, median CD4: 655 cells/mL; detailed characteristics in Table S1, Supplemental Digital Content, http://links.lww.com/QAI/A703) switching to RPV/FTC/TDF between January 2013 and April 2014 were included. Patients’ follow-up was performed up to the end of October 2014 with a median follow-up of 196 days (interquartile range, 84–287). Virological failure was observed in 8 (1.6%) patients: 5 (1.0%) of them discontinued regimen but 3 (0.6%) remained on RPV/FTC/TDF up to the last observation despite failure. Overall, 32 (6.3%) patients discontinued RPV/FTC/ TDF for the following reasons: 5 (1.0%) virological failures, 2 (0.4%) hypersensitivity reactions, 6 (1.2%) gastrointestinal toxicity, 1 (0.2%) liver toxicity, 4 (0.8%) central nervous system toxicity, 5 (1.0%) kidney toxicity, and 9 (1.8%) patient’s decision/lost in follow-up. At survival analysis, the estimated probabilities of virological failure and treatment discontinuation were 1.2% and 5.5% at 6 months and 2.8% and 13.2% at 12 months, respectively. At multivariable Cox analysis, a higher number of previous ARTs [adjusted hazard ratio (aHR): 1.14, 95% confidence interval (CI): 1.07 to 1.21, P , 0.001] and switching from boosted protease inhibitor (PI/r)–based cART (aHR: 1.83, 95% CI: 1.02 to 3.26, P = 0.042) were independently associated with a higher risk of virological failure (see Table S2, Supplemental Digital Content, http://links.lww.com/QAI/A703). In addition, a higher number of preswitch regimens (aHR: 1.06, 95% CI: 1.01 to 1.11, P = 0.014) and CD4 ,200 cells per cubic millimeter count at switch (aHR: 50.22, 95% CI: 10.26 to 245.84, P , 0.001) were independently associated to a higher risk of treatment discontinuation after adjusting for years from HIV diagnosis (see Table S3, Supplemental Digital Content, http://links.lww.com/QAI/A703). S.D.G. received speakers’ honoraria and support for travel meetings from Gilead, Bristol-Myers Squibb, Abbott, Boehringer Ingelheim, JanssenCilag, and GlaxoSmithKline. F.M. received speakers’ honoraria, fees for attending advisory board, travel grants, and research support from ViiV Healthcare, Abbvie, Merck Sharp & Dohme, Gilead, and Bristol-Myers Squibb. M.F. received speakers’ honoraria from Bristol-Myers Squibb, Merck Sharp & Dohme, and JanssenCilag. G.S. received speakers’ honoraria fees for attending advisory board and travel grants from Bristol-Myers Squibb, Janssen-Cilag, and ViiV Healthcare. A.L. received speakers’ honoraria fees for attending advisory board and travel grants from Bristol-Myers Squibb, Janssen-Cilag, Abbvie, ViiV Healthcare, and Merck Sharp & Dohme. A.Am. received speakers’ honoraria, fees for attending advisory board and travel grants and research support from ViiV Healthcare, Merck Sharp & Dohme, Gilead, and Bristol-Myers Squibb. R.C. has been advisor for Gilead and Janssen-Cilag, received speakers’ honoraria from ViiV, Bristol-Myers Squibb, and Janssen-Cilag, and research support from “Fondazione Roma.” A.An. received speakers’ honoraria, fees for attending advisory board, and travel grants and research support from ViiV Healthcare, Abbvie, Merck Sharp & Dohme, Gilead, and BristolMyers Squibb. M.Z. received speakers’ honoraria, fees for attending advisory board, and travel grants from Bristol-Myers Squibb, JanssenCilag, Gilead Science, Abbvie, and ViiV Healthcare. The remaining authors have no funding or conflicts of interest to disclose. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www.jaids.com).