TY - JOUR
T1 - Resistance detected in PBMCs predicts virological rebound in HIV-1 suppressed patients switching treatment
AU - Armenia, Daniele
AU - Zaccarelli, Mauro
AU - Borghi, Vanni
AU - Gennari, William
AU - Di Carlo, Domenico
AU - Giannetti, Alberto
AU - Forbici, Federica
AU - Bertoli, Ada
AU - Gori, Caterina
AU - Fabeni, Lavinia
AU - Pinnetti, Carmela
AU - Marocco, Raffaella
AU - Latini, Alessandra
AU - Ceccherini-Silberstein, Francesca
AU - Mastroianni, Claudio Maria
AU - Mussini, Cristina
AU - Antinori, Andrea
AU - Perno, Carlo Federico
AU - Santoro, Maria Mercedes
PY - 2018/7/1
Y1 - 2018/7/1
N2 - 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.
AB - 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.
KW - Genotypic resistance test
KW - HIV infection
KW - HIV-DNA
KW - PBMC
KW - Treatment switch
KW - Virological rebound
KW - Virologically suppressed patients
UR - http://www.scopus.com/inward/record.url?scp=85046771709&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85046771709&partnerID=8YFLogxK
U2 - 10.1016/j.jcv.2018.04.001
DO - 10.1016/j.jcv.2018.04.001
M3 - Article
AN - SCOPUS:85046771709
VL - 104
SP - 61
EP - 64
JO - Journal of Clinical Virology
JF - Journal of Clinical Virology
SN - 1386-6532
ER -