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Improved Prediction of Salvage Antiretroviral Therapy Outcomes Using Ultrasensitive HIV-1 Drug Resistance Testing

29/05/2014

Christian Pou, et al. Improved Prediction of Salvage Antiretroviral Therapy Outcomes Using Ultrasensitive HIV-1 Drug Resistance Testing. Clinical Infectious Diseases. 29 May 2014

Abstract

 

Background. The clinical relevance of ultrasensitive human immunodeficiency virus type 1 (HIV-1) genotypic resistance testing in antiretroviral treatment (ART)-experienced individuals remains unknown.

Methods. This was a retrospective, multicentre, cohort study in ART-experienced, HIV-1-infected adults who initiated salvage ART including, at least 1 ritonavir-boosted protease inhibitor, raltegravir or etravirine. Presalvage ART Sanger and 454 sequencing of plasma HIV-1 were used to generate separate genotypic sensitivity scores (GSS) using the HIVdb, ANRS, and REGA algorithms. Virological failure (VF) was defined as 2 consecutive HIV-1 RNA levels ≥200 copies/mL at least 12 weeks after salvage ART initiation, whereas subjects remained on the same ART. The ability of Sanger and 454-GSS to predict VF was assessed by receiver operating characteristic (ROC) curves and survival analyses.

Results. The study included 132 evaluable subjects; 28 (21%) developed VF. Using HIVdb, 454 predicted VF better than Sanger sequencing in the ROC curve analysis (area under the curve: 0.69 vs 0.60, Delong test P = .029). Time to VF was shorter for subjects with 454-GSS < 3 vs 454-GSS ≥ 3 (Log-rank P = .003) but not significantly different between Sanger-GSS < 3 and ≥3. Factors independently associated with increased risk of VF in multivariate Cox regression were a 454-GSS < 3 (HR = 4.6, 95 CI, [1.5, 14.0], P = .007), and the number of previous antiretrovirals received (HR = 1.2 per additional drug, 95 CI, [1.1, 1.3], P = .001). Equivalent findings were obtained with the ANRS and REGA algorithms.

Conclusions. Ultrasensitive HIV-1 genotyping improves GSS-based predictions of virological outcomes of salvage ART relative to Sanger sequencing. This may improve the clinical management of ART-experienced subjects living with HIV-1.

 

Read abstract online in Clinical Infectious Diseases

Christian Pou1,2,a, Marc Noguera-Julian1,2,3,a, Susana Pérez-Álvarez1,2, Federico García4, Rafael Delgado5, David Dalmau6,7, Miguel Álvarez-Tejado8, Dimitri Gonzalez9,10, Chalom Sayada9,10, Natalia Chueca4, Federico Pulido5, Laura Ibáñez6, Cristina Rodríguez1,2, Maria Casadellà1,2, José R. Santos2,11, Lidia Ruiz1,2, Bonaventura Clotet1,2,3,11, and Roger Paredes1,2,3,11

1IrsiCaixa AIDS Research Institute - HIVACAT, Hospital Universitari Germans Trias i Pujol, Badalona 2Universitat Autònoma de Barcelona, Cerdanyola del Vallès 3Universitat de Vic-Universitat Central de Catalunya, Vic 4Microbiology and Molecular Biology Department, Hospital Universitario San Cecilio, Granada 5Laboratory of Molecular Microbiology, Instituto de Investigación Biomedica Hospital 12 de Octubre (i + 12), Madrid 6HIV/AIDS Department, Hospital Universitari MútuaTerrassa 7Universitat de Barcelona, Terrassa 8Roche Diagnostics, SL, Sant Cugat del Vallès 9ABL SA, Barcelona, Spain 10ABL SA, Luxembourg, Luxembourg 11HIV Unit, Internal Medicine Department, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain

Grupos de IrsiCaixa vinculados: Genómica MicrobianaServicios Cientificotécnicos