Twenty‐four‐week efficacy and safety of switching virologically suppressed HIV‐1‐infected patients from nevirapine immediate release 200 mg twice daily to nevirapine extended release 400 mg once daily (TRANxITION)

Abstract

ObjectivesOnce-daily (qd) antiretroviral therapies improve convenience and adherence. If found to be effective, nevirapine extended release (NVP XR) will confer this benefit. The TRANxITION trial examined the efficacy and safety of switching virologically suppressed patients from NVP immediate release (NVP IR) 200 mg twice daily to NVP XR 400 mg qd. MethodsAn open-label, parallel-group, noninferiority, randomized (2:1 NVP XR:NVP IR) study was performed. Adult HIV-1-infected patients receiving NVP IR plus a fixed-dose nucleoside reverse transcriptase inhibitor (NRTI) combination of lamivudine (3TC)/abacavir (ABC), tenofovir (TDF)/emtricitabine (FTC) or 3TC/zidovudine (ZDV) with undetectable viral load (VL) were enrolled in the study. The primary endpoint was continued virological suppression with VL < 50 HIV-1 RNA copies/mL up to week 24 (calculated using a time to loss of virological response algorithm). Cochran's statistic (background regimen adjusted) was used to test noninferiority. Adverse events (AEs) were recorded. ResultsAmong 443 randomized patients, continued virological suppression was observed in 93.6% (276 of 295) of NVP XR-and 92.6% (137 of 148) of NVP IR-treated patients, an observed difference of 1% [95% confidence interval (CI) -4.3, 6.0] at 24 weeks of follow-up. Noninferiority (adjusted margin of -10%) of NVP XR to NVP IR was robust and further supported by SNAPSHOT analysis. Division of Acquired Immunodeficiency Syndrome (DAIDS) grade 3 and 4 events were similar for the NVP XR and NVP IR groups (3.7 vs. 4.1%, respectively), although overall AEs were higher in the NVP XR group (75.6 vs. 60.1% for the NVP-IR group). ConclusionsNVP XR administered once daily resulted in continued virological suppression at week 24 that was noninferior to that provided by NVP IR, with similar rates of moderate and severe AEs. The higher frequency of overall AEs with NVP XR may be a consequence of the open-label design.

Efficacy and safety of switching from nevirapine immediate-release twice daily to nevirapine extended-release once daily in virologically suppressed HIV-infected patients: a retrospective cohort study in Taiwan

“…Because HIV-infected patients regularly visit our infectious diseases department every 1–3 months, we retrospectively screened all HIV-infected patients who were receiving NVP-IR-containing cART during the period from April 1, 2013 to June 30, 2013. Inclusion criteria for virological suppression were patients who were receiving NVP-IR plus two nucleos(t)ide reverse-transcriptase inhibitors, for a preceding minimum of 18 weeks, with undetectable (<50 HIV-1 RNA copies/mL) HIV-1 viral load (VL) in the previous 1–4 months [12]. Exclusion criteria were age < 18 years, pregnancy, or patients whose regimen included 400 mg NVP-IR once daily/switching from NVP-IR to NVP-XR/change of the NRTI backbone of combination regimens between July 1, 2013, and March 31, 2015.…”

“…To further simplify treatment regimens, a new extended-release (XR) formulation was developed [9, 10]. In phase III clinical trials, 400 mg NVP-XR once daily was found not inferior to 200 mg NVP-IR twice daily in terms of virological suppression in treatment-naïve patients (VERxVE study) [11] and in virologically suppressed patients who were switched from NVP-IR to NVP-XR (TRANxITION study) [12]. …”

“…In addition, previous PK studies of NVP have demonstrated a lower C trough with 400 mg NVP-XR once daily compared with 200 mg NVP-IR twice daily [11, 12, 23]. Therefore, the question remains whether the non-inferior efficacy and safety results of switching virologically suppressed HIV-1-infected patients from NVP-IR to NVP-XR demonstrated in the TRANxITION study conducted in Europe and North America [12] are also applicable to virologically suppressed HIV-infected patients in Taiwan.…”

Considerations on the New Nevirapine

“…After adjustment for background therapy, the difference was 1.0% (95% CI: À4.3%-6.0%), indicating NVP-XR was noninferior to NVP-IR. 5 The proportion of patients experiencing division of AIDS (DAIDS) grade 3 or 4 events was similar in the NVP-XR and NVP-IR arms (3.7% vs 4.1%, respectively), although the number of patients reporting any AEs-whether or not defined as possibly drug-related by the treating physician-was greater in the NVP-XR than in the NVP-IR arm, perhaps because of the open-label study design. 5 The rates of AEs for 6 system organ classes that were greater in patients receiving NVP-XR at 24 weeks were followed up at 48 weeks ( Table 2).…”

“…5 The proportion of patients experiencing division of AIDS (DAIDS) grade 3 or 4 events was similar in the NVP-XR and NVP-IR arms (3.7% vs 4.1%, respectively), although the number of patients reporting any AEs-whether or not defined as possibly drug-related by the treating physician-was greater in the NVP-XR than in the NVP-IR arm, perhaps because of the open-label study design. 5 The rates of AEs for 6 system organ classes that were greater in patients receiving NVP-XR at 24 weeks were followed up at 48 weeks ( Table 2). Note that the analysis of the differences in the rates of AEs was limited to AEs considered mild or moderate at 24 weeks because of the very low number of serious AEs in any category.…”