TRANxITION 144‐week results: switching virologically stable HIV patients from immediate‐release nevirapine (NVP IR) to extended‐release NVP (XR)

Abstract

Purpose of the study

TRANxITION compared the efficacy and safety of switching virologically suppressed patients from NVP IR (200 mg BID) to NVP XR (400 mg QD) and demonstrated the non‐inferior efficacy of NVP XR in virologically suppressed patients. Here, post‐48‐week safety and efficacy results of patients initially randomized to NVP IR and allowed to switch to NVP XR after 48 weeks, were compared to patients on NVP XR throughout the study.

Methods

TRANxITION was an open‐label, parallel‐group, non‐inferiority clinical trial where adult HIV‐1 patients receiving NVP IR plus a fixed‐dose NRTI combination of lamivudine (3TC)/abacavir (ABC), tenofovir (TDF)/emtricitabine (FTC) or 3TC/zidovudine (ZDV), with undetectable viral loads (VL) were initially randomized (2:1) to NVP XR or NVP IR. After week 48, patients initially randomized to NVP IR were allowed to switch to NVP XR. Primary endpoint was continued virologic suppression (VL<50 copies/mL) at week 24. Secondary endpoints included long‐term follow‐up at 48 and 144 weeks.

Summary of results

At week 48, proportions of patients with virologic response (LLOQ = 50 copies/mL TaqMan, FAS) were 88.5% (131/148) NVP IR BID arm, and 88.8% (262/295) NVP XR QD, with an observed difference of 0.3% (95% CI −6.1, 6.7). Division of Acquired Immunodeficiency Syndrome (DAIDS) grade 3 and 4 events were similar for the NVP XR and NVP IR groups at week 48, 6.4% (19/295) vs. 6.1% (9/148) respectively, although serious AEs were slightly higher in the NVP XR group (10.2%, 30/295, vs. 8.1%, 12/148 for the NVP‐IR group). After week 48, all but 13 patients in the NVP IR arm switched to NVP XR. At week 144, proportions of patients with virologic response were 115/121 (95.0%, patients switching from IR to XR after week 48 [IRpost48XR]), and 238/250 (95.2%, patients on XR throughout [XRpost48]). DAIDS grade 3 and 4 events were similar for both post‐week‐48 XR groups at week 144, with (10/130, 7.7%, [IRpost48XR] vs. (31/276, 11.2% [XRpost48]), while serious AEs were higher in the XRpost48 patients (54/276, 19.6% vs. 17/130, 13.1% for the IRpost48XR group).

Conclusions

NVP XR QD resulted in continued virologic suppression at weeks 48 and 144. While fewer patients remained in the study post‐week 48, both XR groups had high virologic response rates. Rates of serious AEs were modestly higher than seen at week 24 in both post‐week‐48 XR arms up to week 144, most likely due to the open‐label design of the study.