Suchergebnisse

BackgroundCD4 and viral loads are used in clinical trials as surrogate endpoints for assessing efficacy of newly available antiretrovirals. If antiretrovirals act through other pathways or negatively affect the risk of disease this would not be identified prior to licensing. The aims of this study were to investigate the CD4 and viral load specific rates of fatal and non‐fatal AIDS and non‐AIDS events according to current antiretrovirals.MethodsPoisson regression was used to compare overall events (fatal or non‐fatal AIDS, non‐AIDS or death), AIDS events (fatal and non‐fatal) or non‐AIDS events (fatal or non‐fatal) for specific nucleoside pairs and third drugs used with>1000 person‐years of follow‐up (PYFU) after January 1st 2001.Results9801 patients were included. The median baseline date was January 2004 (interquartile range [IQR] January 2001–February 2007), age was 40.4 (IQR 34.6–47.3 years), and time since starting cART was 3.3 (IQR 0.9–5.1 years). At baseline, the median nadir CD4 was 162 (IQR 71–257/mm3), baseline CD4 was 390 (IQR 249–571/mm3), viral load was 1.9 (IQR 1.7–3.3 log10copies/ml) and 2961 (30.2%) had a prior AIDS diagnosis and 6.4 years) prior to baseline. During 42372.5 PYFU, 1203 (437 AIDS and 766 non‐AIDS) events occurred. The overall event rate was 2.8 per 100 PYFU (95% confidence interval [CI] 2.7–3.0), of AIDS events was 1.0 (95% CI 0.9–1.1) and of non‐AIDS events was 1.8 (95% CI 1.7–1.9). Of the AIDS events, 53 (12.1%)were fatal as were 239 (31.2%) of the non‐AIDS events. After adjustment, there was weak evidence of a difference in the overall events rates between nucleoside pairs (global p‐value=0.084), and third drugs (global p‐value=0.031). Compared to zidovudine/lamivudine, patients taking abacavir/lamivudine (adjusted incidence rate ratio [aIRR] 1.22; 95% CI 0.99–1.49) and abacavir plus one other nucleoside (aIRR 1.51; 95% CI 1.14–2.02) had an increased incidence of overall events. Comparing the third drugs, those taking unboosted atazanavir had an increased incidence of overall events compared to those taking efavirenz (aIRR 1.46; 95% CI 1.09–1.95)(Figure).imageConclusionsThere was little evidence of substantial differences between antiretrovirals in the incidence of fatal and non‐fatal AIDS and non‐AIDS events for a given CD4 or viral load, suggesting there are unlikely to be major unidentified adverse effects of specific antiretrovirals, although confounding by indication cannot be ruled out.

Publisher's version (útgefin grein) ; Objectives There are currently few data on the long‐term risk of cancer and death in individuals taking raltegravir (RAL). The aim of this analysis was to evaluate whether there is evidence for an association. Methods The EuroSIDA cohort was divided into three groups: those starting RAL‐based combination antiretroviral therapy (cART) on or after 21 December 2007 (RAL); a historical cohort (HIST) of individuals adding a new antiretroviral (ARV) drug (not RAL) to their cART between 1 January 2005 and 20 December 2007, and a concurrent cohort (CONC) of individuals adding a new ARV drug (not RAL) to their cART on or after 21 December 2007. Baseline characteristics were compared using logistic regression. The incidences of newly diagnosed malignancies and death were compared using Poisson regression. Results The RAL cohort included 1470 individuals [with 4058 person‐years of follow‐up (PYFU)] compared with 3787 (4472 PYFU) and 4467 (10 691 PYFU) in the HIST and CONC cohorts, respectively. The prevalence of non‐AIDS‐related malignancies prior to baseline tended to be higher in the RAL cohort vs. the HIST cohort [adjusted odds ratio (aOR) 1.31; 95% confidence interval (CI) 0.95–1.80] and vs. the CONC cohort (aOR 1.89; 95% CI 1.37–2.61). In intention‐to‐treat (ITT) analysis (events: RAL, 50; HIST, 45; CONC, 127), the incidence of all new malignancies was 1.11 (95% CI 0.84–1.46) per 100 PYFU in the RAL cohort vs. 1.20 (95% CI 0.90–1.61) and 0.83 (95% CI 0.70–0.99) in the HIST and CONC cohorts, respectively. After adjustment, there was no evidence for a difference in the risk of malignancies [adjusted rate ratio (RR) 0.73; 95% CI 0.47–1.14 for RALvs. HIST; RR 0.95; 95% CI 0.65–1.39 for RALvs. CONC] or mortality (adjusted RR 0.87; 95% CI 0.53–1.43 for RALvs. HIST; RR 1.14; 95% CI 0.76–1.72 for RALvs. CONC). Conclusions We found no evidence for an oncogenic risk or poorer survival associated with using RAL compared with control groups. ; EuroSIDA was supported by the European Union's Seventh Framework Programme for research, technological development and demonstration under EuroCoord grant agreement no. 260694. Current support includes unrestricted grants from Bristol‐Myers Squibb, Gilead, GlaxoSmithKline LLC, Janssen R&D, Merck and Co. Inc. and Pfizer Inc. The participation of centres from Switzerland was supported by The Swiss National Science Foundation (Grant 108787). The study is also supported by a grant (grant number DNRF126) from the Danish National Research Foundation. ; Peer Reviewed