Switching at Low HIV-1 RNA into Fixed Dose Combinations: TDF/FTC/RPV is non-inferior to TDF/FTC/EFV in first-line suppressed patients living with HIV

Abstract

Background In low- and middle-income countries (LMICs), a substantial unmet need for affordable single-tablet regimen (STR) options remains. Rilpivirine (RPV, TMC278) is formulated in a low-cost STR with tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC). Objectives Switching at Low HIV-1 RNA into Fixed Dose Combinations (SALIF) compared RPV with efavirenz (EFV), both as STRs with TDF and FTC, in maintaining virologic suppression. Methods SALIF was a phase 3b, randomised, open-label, non-inferiority study in virologically suppressed adults (HIV-1 RNA < 50 copies/mL) on non-nucleoside reverse transcriptase inhibitor (NNRTI)-based first-line antiretroviral therapy (ART) in Cameroon, Kenya, Senegal, South Africa, Uganda and Thailand. Patients ( N = 426), stratified by NNRTI use, were randomised 1:1 to receive TDF/FTC/RPV (300/200/25 mg qd) or TDF/FTC/EFV (300/200/600 mg qd). Primary endpoint was proportion of patients with virologic suppression (HIV-1 RNA < 400 copies/mL) at week 48 (intent-to-treat, modified Food and Drug Administration Snapshot, 10% non-inferiority margin). Results Patients received TDF/FTC/RPV ( n = 213) or TDF/FTC/EFV ( n = 211). At week 48, virologic suppression was maintained in 200/213 (93.9%) patients in the RPV arm and 203/211 (96.2%) in the EFV arm (difference –2.3%; 95% confidence interval: −6.4, +1.8), demonstrating non-inferiority of TDF/FTC/RPV. One patient in each arm experienced virologic failure without treatment-emergent resistance. Twenty-seven patients discontinued prematurely (8.0% RPV vs. 4.7% EFV), the most frequent reasons being adverse events (3.3% vs. 0.5%, respectively), site closure (1.9% vs. 0.5%), loss to follow-up (0.9% vs. 1.4%) and consent withdrawal (0.9% vs. 1.4%). Conclusion In adults with suppressed viral load on first-line NNRTI-based ART in LMICs, switching to an STR of TDF/FTC/RPV was non-inferior to TDF/FTC/EFV in maintaining high rates of viral suppression with a comparable tolerability profile.

Prognostic model for nephrotoxicity among HIV-positive Zambian adults receiving tenofovir disoproxil fumarate-based antiretroviral therapy

“…Additionally, compared to baseline, there was a 15 mL/min/1.73m 3 reduction in eGFR observed at 3-months of therapy, consistent with findings from Japan that suggest a rapid decline in eGFR with TDF exposure [26]. There was also an increase in CD4+ count by 86 cells/L observed at three months of TDF therapy, consistent with the CD4+ immune cell improvement often seen in TDF-based therapy [44,45].…”

Efficacy and Safety of Rilpivirine-Based Antiretroviral Therapy in Treatment-Naïve and Treatment-Experienced HIV-1-Positive Patients: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

“…Any disagreements were resolved by consensus. Eighteen articles met the inclusion criteria and were included in the systematic review [3][4][5][6][7][8][9][10][11][12][13][14]28,[32][33][34][35][36] (Table 1). Four of these articles were presented in tables and were not included in the quantitative metaanalyses of the efficacy and safety outcomes.…”

“…Rilpivirine (RPV; TMC278; Edurant®) is a secondgeneration non-nucleoside reverse-transcriptase inhibitor (NNRTI) with activity against many viral strains resistant to previous NNRTIs and a moderatehigh genetic barrier to resistance development [1,2]. RPV efficacy and safety have been assessed in registrative randomized controlled clinical trials (RCTs) in HIV-positive treatment-naïve [3][4][5][6][7] and treatmentexperienced patients [8][9][10][11][12][13][14] with documented longterm efficacy and tolerability. Real-life data from observational studies [15][16][17][18][19][20][21] eventually confirmed these results.…”

“…were used when reporting results for lipid values, as the publication of the pooled analysis did not detail such quantitative information [36]) and the publications at 148 weeks of follow-up of the SWORD 1-2 trials [35] and at 192 weeks of the TMC278-C204 trial [6] (which were not used in the meta-analyses, as no other study had data for a comparable follow-up period). Thus, a total of 14 publications [5,[7][8][9][10][11][12][13][14]28,[32][33][34]36], which provided results on 12 distinct RCTs at 48 and/or 96 (± 8) weeks of follow-up, were included in the metaanalyses. The data were extracted from the selected articles in a standardized format by 2 independent reviewers.…”

Use of rilpivirine in HIV-1-infected individuals in routine clinical practice from 2012 to 2017 in France

“…1,2,3 Others clinical trials have shown that the rilpivirine/emtricitabine/TDF combination can maintain virological suppression in antiretroviral (ARV)-experienced virologically-controlled PLHIV. [4][5][6][7][8] In recent trials, the dual therapy dolutegravir/rilpivirine was non-inferior to a current triple antiretroviral therapy (ART) regimen in ARV-experienced virologically-controlled PLHIV at week 48 and efficacy and safety were maintained at week 100. 9,10 It is important to obtain data from real-life settings to assess how rilpivirine is used in routine care and evaluate its virological efficacy, as a complement to data from clinical trials.…”