Viral suppression rates in salvage treatment with raltegravir improved with the administration of genotypic partially active or inactive nucleoside/tide reverse transcriptase inhibitors

Publication

Viral suppression rates in salvage treatment with raltegravir improved with the administration of genotypic partially active or inactive nucleoside/tide reverse transcriptase inhibitors

Journal Paper/Review - May 1, 2011

Scherrer Alexandra U, Günthard Huldrych F, Ledergerber Bruno, Bernasconi Enos, Vernazza Pietro, Battegay Manuel, Cavassini Matthias, Hirschel Bernard, Garzoni Christian, Bürgisser Philippe, Klimkait Thomas, Yerly Sabine, Böni Jürg, von Wyl Viktor, Swiss HIV Cohort Study (SHCS)

Citation

Scherrer A, Günthard H, Ledergerber B, Bernasconi E, Vernazza P, Battegay M, Cavassini M, Hirschel B, Garzoni C, Bürgisser P, Klimkait T, Yerly S, Böni J, von Wyl V, Swiss HIV Cohort Study (SHCS). Viral suppression rates in salvage treatment with raltegravir improved with the administration of genotypic partially active or inactive nucleoside/tide reverse transcriptase inhibitors. J Acquir Immune Defic Syndr 2011; 57:24-31.

Type

Journal Paper/Review (English)

Journal

J Acquir Immune Defic Syndr 2011; 57

Publication Date

May 1, 2011

Issn Electronic

1944-7884

Pages

24-31

Brief description/objective

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.