Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology · 2018
Resistance detected in PBMCs predicts virological rebound in HIV-1 suppressed patients switching treatment.
СтатьяНаблюдательное исследованиеПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Armenia Daniele, Zaccarelli Mauro, Borghi Vanni, Gennari William, Di Carlo Domenico, Giannetti Alberto, Forbici Federica, Bertoli Ada, Gori Caterina, Fabeni Lavinia, Pinnetti Carmela, Marocco Raffaella, Latini Alessandra, Ceccherini-Silberstein Francesca, Mastroianni Claudio Maria, Mussini Cristina, Antinori Andrea, Perno Carlo Federico, Santoro Maria Mercedes
Аннотация
BACKGROUND: Genotypic resistance test (GRT) performed in peripheral blood mononuclear cells (PBMC) represents a chance to evaluate resistance in virologically suppressed HIV infected patients.
OBJECTIVES: To evaluate the impact of baseline resistance detected through PBMC GRT on virological rebound after switching treatment.
STUDY DESIGN: Baseline genotypic susceptibility scores (GSS) from PBMC GRT (DNA-GSS) and from previous cumulative plasma GRTs (when available, pRNA-GSS) were evaluated. Survival analysis was used to assess the probability and predictors of virological rebound (VR).
RESULTS: 227 virologically suppressed patients were analysed. Twenty-four months after switching therapy, the probability of VR was 15.3%. Patients showing an intermediate or full resistant DNA-GSS had a higher probability of experiencing VR compared to those carrying a fully susceptible DNA-GSS (27.2% vs. 13.7%, p = 0.001). By multivariable Cox regression, patients with an intermediate/full resistant DNA-GSS, with a nadir CD4 count <100 cell/mm3 and with a shorter time of previous virological suppression showed a higher adjusted hazard of experiencing VR. In a sub-group of 114 patients with previous plasma GRTs available, patients with an intermediate or fully resistance showed by both GSSs (from plasma and PBMCs) had the highest probability of experiencing VR.
CONCLUSIONS: Resistance detected in proviral DNA, together with a low nadir CD4 count and a short previous virological control, predicts VR after therapy switching in virologically suppressed patients. PBMC GRT can be a useful tool for tailoring treatment switch, especially if paired with information about previous cumulative resistance and previous viro-immunological history.
OBJECTIVES: To evaluate the impact of baseline resistance detected through PBMC GRT on virological rebound after switching treatment.
STUDY DESIGN: Baseline genotypic susceptibility scores (GSS) from PBMC GRT (DNA-GSS) and from previous cumulative plasma GRTs (when available, pRNA-GSS) were evaluated. Survival analysis was used to assess the probability and predictors of virological rebound (VR).
RESULTS: 227 virologically suppressed patients were analysed. Twenty-four months after switching therapy, the probability of VR was 15.3%. Patients showing an intermediate or full resistant DNA-GSS had a higher probability of experiencing VR compared to those carrying a fully susceptible DNA-GSS (27.2% vs. 13.7%, p = 0.001). By multivariable Cox regression, patients with an intermediate/full resistant DNA-GSS, with a nadir CD4 count <100 cell/mm3 and with a shorter time of previous virological suppression showed a higher adjusted hazard of experiencing VR. In a sub-group of 114 patients with previous plasma GRTs available, patients with an intermediate or fully resistance showed by both GSSs (from plasma and PBMCs) had the highest probability of experiencing VR.
CONCLUSIONS: Resistance detected in proviral DNA, together with a low nadir CD4 count and a short previous virological control, predicts VR after therapy switching in virologically suppressed patients. PBMC GRT can be a useful tool for tailoring treatment switch, especially if paired with information about previous cumulative resistance and previous viro-immunological history.