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Resistance Rates and Patterns Similar With Extended-
and Immediate-Release Nevirapine
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51st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), September 17-20, 2011, Chicago
Mark Mascolini
Among genotyped participants in the VERxVE trial comparing once-daily extended-release nevirapine (NVP-XR) with the twice-daily immediate-release formulation (NVP-IR), resistance mutations emerged at similar rates in the two study arms, and resistance patterns were similar in the two arms [1].
The double-blind, double-dummy VERxVE noninferiority trial compared NVP-XR at a dose of 400-mg once daily with NVP-IR taken at 200 mg twice daily by 1011 antiretroviral-naive people, always with tenofovir/emtricitabine [2]. At enrollment all study participants had a viral load above 1000 copies/mL and a CD4 count below 400 in men (85% of study participants) and below 250 in women. At the 48-week point, 80% in the NVP-XR group and 79% in the NVP-IR group had a viral load below 50 copies. The two groups did not differ in rates of adverse events, severe events, events leading to discontinuation, or lipid changes.
The resistance study involved VERxVE participants who met one of four virologic inclusion criteria:
Responders: Consecutive viral loads below 50 copies 2 or more weeks apart but with a transient increase in viremia (a blip)
Therapy discontinuation: Stopping treatment for reasons other than efficacy
Partial responders: Viral load drop but not below 400 copies
Rebounders: Viral load drop below 400 copies but later above 500 copies
Of the 86 people (8.5% of 1011) who met these criteria, 4 were responders, 28 discontinued therapy, 23 were partial responders, and 31 were rebounders. Of these 86 people, 32 of 505 (6.3%) took NVP-XR and 54 of 506 (10.7%) took NVP-IR. Of the 54 partial responders and rebounders, all met virologic failure criteria with a viral load at or above 50 copies/mL.
Among these 86 genotyped people, 11 of 32 (34.4%) taking NPV-XR and 20 of 54 (37.0%) taking NVP-IR had no mutations conferring resistance to nonnucleosides. Thirteen of 32 (40.6%) in the NVP-XR group and 23 of 54 (42.6%) in the NVP-IR group had no nucleoside or nonnucleoside mutations.
The most frequent nonnucleoside mutation with both formulations was Y181C. The XR and IR groups did not differ significantly in proportions with only etravirine mutations (6.3% and 5.6%), only efavirenz mutations (0% in both groups), only nevirapine and etravirine mutations (25.0% and 25.9%), or nevirapine, etravirine, and efavirenz mutations (21.9% and 18.5%).
The most frequent nucleoside mutation with either nevirapine formulation was the emtricitabine-related M184I/V change (43.8% NVP-XR and 44.4% NVP-IR). Respective proportions with K65R were 18.8% and 13.0% and with K65N 3.1% and 0%.
The investigators concluded that these similar mutation profiles with NVP-XR and NVP-IR are the patterns that would be expected upon failure of a nevirapine regimen.
References
1. Bethell R, Hall D, Scherer J, et al. A retrospective analysis comparing the frequency of emergent resistance in patients receiving nevirapine extended release QD or nevirapine immediate release BID who experienced virological failure or transient increase in viral load in the VERxVE sub-study. 51st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). September 17-20, 2011. Chicago. Abstract H1-372.
2. Gathe J, Bogner J, Santiago S, et al. Comparison of 48 week efficacy and safety of 400 mg QD nevirapine extended release formulation (Viramune XR) versus 200 mg BID nevirapine immediate release formulation (Viramune IR) in combination with Truvada in antiretroviral naive HIV-1 infected patients (VERxVE). XVIII International AIDS Conference. July 18-23, 2010. Vienna. Abstract THLBB202.
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