Battegay M, Bernasconi E, Böni J, Bucher HC, Bürgisser P, Calmy A, Cattacin S, Cavassini M, Dubs R, Egger M, Elzi L, Fischer M, Flepp M, Fontana A, Francioli P, Furrer H, Fux CA, Gorgievski M, Günthard H, Hirsch HH, Hirschel B, Hösli I, Kahlert C, Kaiser L, Karrer U, Kind C, Klimkait T, Ledergerber B, Martinetti G, Müller N, Nadal D, Paccaud F, Pantaleo G, Rauch A, Regenass S, Rickenbach M, Rudin C, Schmid P, Schultze D, Schüpbach J, Speck R, de Tejada BM, Taffé P, Telenti A, Trkola A, Vernazza P, Weber R, Yerly S.
Source
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zürich, University of Zürich, Zürich, Switzerland. alexandra.scherrer@usz.ch
Abstract
BACKGROUND:
Nucleoside reverse transcriptase inhibitors (NRTIs) are often administered in salvage therapy even if genotypic resistance tests (GRTs) indicate high-level resistance, but little is known about the benefit of these additional NRTIs.
METHODS:
The effect of <2 compared with 2 NRTIs on viral suppression (HIV-1 RNA < 50 copies/mL) at week 24 was studied in salvage patients receiving raltegravir. Intent-to-treat and per-protocol analyses were performed; last observation carried forward imputation was used to deal with missing information. Logistic regressions were weighted to create a pseudopopulation in which the probability of receiving <2 and 2 NRTIs was unrelated to baseline factors predicting treatment response.
RESULTS:
One-hundred thirty patients were included, of whom 58.5% (n = 76) received <2 NRTIs. NRTIs were often replaced by other drug classes. Patients with 2 NRTIs received less additional drug classes compared with patients with <2 NRTIs [median (IQR): 1 (1-2) compared with 2 (1-2), P Wilcoxon < 0.001]. The activity of non-NRTI treatment components was lower in the 2 NRTIs group compared with the <2 NRTIs group [median (IQR) genotypic sensitivity score: 2 (1.5-2.5) compared with 2.5 (2-3), P Wilcoxon < 0.001]. The administration of <2 NRTIs was associated with a worse viral suppression rate at week 24. The odds ratios were 0.34 (95% confidence interval: 0.13 to 0.89, P = 0.027) and 0.19 (95% confidence interval: 0.05 to 0.79, P = 0.023) when performing the last observation carried forward and the per-protocol approach, respectively.
CONCLUSIONS:
Our findings showed that partially active or inactive NRTIs contribute to treatment response, and thus the use of 2 NRTIs in salvage regimens that include raltegravir seems warranted.