ORCID Profile
0000-0002-7644-3647
Current Organisations
Università degli Studi di Milano
,
Epatocentro Ticino
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Publisher: Public Library of Science (PLoS)
Date: 31-03-2015
Publisher: Oxford University Press (OUP)
Date: 15-09-2009
DOI: 10.1086/605447
Publisher: Public Library of Science (PLoS)
Date: 13-03-2014
Publisher: Wiley
Date: 31-08-2011
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-11-2008
Publisher: Oxford University Press (OUP)
Date: 15-04-2008
DOI: 10.1086/529523
Abstract: Background and methodsThe SMART study compared 2 strategies for using antiretroviral therapy—drug conservation (DC) and viral suppression (VS)—in 5472 human immunodeficiency virus (HIV)–infected patients with CD4+ cell counts & cells/μL. Rates and predictors of opportunistic disease or death (OD/death) and the relative risk (RR) in DC versus VS groups according to the latest CD4+ cell count and HIV RNA level are reported ResultsDuring a mean of 16 months of follow-up, DC patients spent more time with a latest CD4+ cell count & cells/μL (for DC vs. VS, 31% vs. 8%) and with a latest HIV RNA level & copies/mL (71% vs. 28%) and had a higher rate of OD/death (3.4 vs. 1.3/100 person-years) than VS patients. For periods of follow-up with a CD4+ cell count & cells/μL, rates of OD/death were increased but similar in the 2 groups (5.7 vs. 4.6/100 person-years), whereas the rates were higher in DC versus VS patients (2.3 vs. 1.0/100 person-years RR, 2.3 [95% confidence interval, 1.5–3.4]) for periods with the latest CD4+ cell count ⩾350 cells/μL—an increase explained by the higher HIV RNA levels in the DC group ConclusionsThe higher risk of OD/death in DC patients was associated with (1) spending more follow-up time with relative immunodeficiency and (2) living longer with uncontrolled HIV replication even at higher CD4+ cell counts. Ongoing HIV replication at a given CD4+ cell count places patients at an excess risk of OD/death Trial registrationClinicalTrials.gov identifier: NCT00027352
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 22-05-2014
Abstract: In the general population, raised levels of inflammatory markers are stronger predictors of fatal than nonfatal cardiovascular disease ( CVD ) events. People with HIV have elevated levels of interleukin‐6 ( IL ‐6), high‐sensitivity C‐reactive protein (hs CRP ), and D‐dimer HIV ‐induced activation of inflammatory and coagulation pathways may be responsible for their greater risk of CVD . Whether the enhanced inflammation and coagulation associated with HIV is associated with more fatal CVD events has not been investigated. Biomarkers were measured at baseline for 9764 patients with HIV and no history of CVD . Of these patients, we focus on the 288 that experienced either a fatal (n=74) or nonfatal (n=214) CVD event over a median of 5 years. Odds ratios ( OR s) (fatal versus nonfatal CVD ) (95% confidence intervals [ CIs ]) associated with a doubling of IL ‐6, D‐dimer, hs CRP , and a 1‐unit increase in an IL ‐6 and D‐dimer score, measured a median of 2.6 years before the event, were 1.39 (1.07 to 1.79), 1.40 (1.10 to 1.78), 1.09 (0.93 to 1.28), and 1.51 (1.15 to 1.97), respectively. Of the 214 patients with nonfatal CVD , 23 died during follow‐up. Hazard ratios (95% CI ) for all‐cause mortality were 1.72 (1.28 to 2.31), 1.73 (1.27 to 2.36), 1.44 (1.15 to 1.80), and 1.88 (1.39 to 2.55), respectively, for IL ‐6, D‐dimer, hs CRP , and the IL ‐6 and D‐dimer score. Higher IL ‐6 and D‐dimer levels reflecting enhanced inflammation and coagulation associated with HIV are associated with a greater risk of fatal CVD and a greater risk of death after a nonfatal CVD event. URL: www.clinicaltrial.gov Unique identifier: SMART: NCT00027352, ESPRIT: NCT00004978, SILCAAT: NCT00013611.
Publisher: American College of Physicians
Date: 02-09-2008
DOI: 10.7326/0003-4819-149-5-200809020-00003
Abstract: Episodic use of antiretroviral therapy guided by CD4+ cell counts is inferior to continuous antiretroviral therapy. To determine whether reinitiating continuous antiretroviral therapy in patients who received episodic treatment reduces excess risk for opportunistic disease or death. Randomized, controlled trial. Sites in 33 countries. 5472 HIV-infected in iduals with CD4(+) cell counts greater than 0.350 x 10(9) cells/L enrolled from January 2002 to January 2006. Episodic or continuous antiretroviral therapy initially, followed by continuous therapy in participants previously assigned to episodic treatment. Opportunistic disease or death was the primary outcome. Eighteen months after the recommendation to reinitiate continuous therapy, mean CD4+ cell counts were 0.152 x 10(9) cells/L (95% CI, 0.136 to 0.167 x 10(9) cells/L) less in participants previously assigned to episodic treatment (P < 0.001). The proportion of follow-up time spent with CD4+ cell counts of 0.500 x 10(9) cells/L or more and HIV RNA levels of 400 copies/mL or less was 29% for participants initially assigned to episodic therapy and 66% for those assigned to continuous therapy. Participants who reinitiated continuous therapy experienced rapid suppression of HIV RNA levels (89.7% with HIV RNA levels < or =400 copies/mL after 6 months), but CD4+ cell counts after 6 months remained 0.140 x 10(9) cells/L below baseline. The hazard ratio (episodic versus continuous treatment) for opportunistic disease or death decreased after the recommendation to reinitiate continuous therapy (from 2.5 [CI, 1.8 to 3.5] to 1.4 [CI, 1.0 to 2.0] P = 0.033 for difference). The residual excess risk was attributable to failure to reinitiate therapy by some participants and slow recovery of CD4+ cell counts for those who reinitiated therapy. Follow-up was too short to assess the full effect of switching from episodic to continuous antiretroviral therapy. Reinitiating continuous antiretroviral therapy in patients previously assigned to episodic treatment reduced excess risk for opportunistic disease or death, but excess risk remained. Episodic antiretroviral therapy, as used in the SMART study, should be avoided.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-01-2009
Publisher: Oxford University Press (OUP)
Date: 15-04-2008
DOI: 10.1086/586713
Abstract: The SMART study randomized 5,472 human immunodeficiency virus (HIV)-infected patients with CD4+ cell counts >350 cells/microL to intermittent antiretroviral therapy (ART the drug conservation [DC] group) versus continuous ART (the viral suppression [VS] group). In the DC group, participants started ART when the CD4+ cell count was or= 6 months (n=228) were analyzed. The following clinical outcomes were assessed: (i) opportunistic disease (OD) or death from any cause (OD/death) (ii) OD (fatal or nonfatal) (iii) serious non-AIDS events (cardiovascular, renal, and hepatic disease plus non-AIDS-defining cancers) and non-OD deaths and (iv) the composite of outcomes (ii) and (iii). A total of 477 participants (228 in the DC group and 249 in the VS group) were followed (mean, 18 months). For outcome (iv), 21 and 6 events occurred in the DC (7 in ART-naive participants and 14 in those who had not received ART for >or= 6 months) and VS (2 in ART-naive participants and 4 in those who had not received ART for 6 months) groups, respectively. Hazard ratios for DC vs. VS by outcome category were as follows: outcome (i), 3.47 (95% confidence interval [CI], 1.26-9.56 p=.02) outcome (ii), 3.26 (95% CI, 1.04-10.25 p=.04) outcome (iii), 7.02 (95% CI, 1.57-31.38 p=.01) and outcome (iv), 4.19 (95% CI, 1.69-10.39 p=.002 ). Initiation of ART at CD4+ cell counts >350 cells/microL compared with <250 cells/microL may reduce both OD and serious non-AIDS events. These findings require validation in a large, randomized clinical trial.
No related grants have been discovered for Lorenzo Magenta.