Browsing by Author "Maltez, Fernando (6602422083)"

Background: CD4 cell count 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 increase the risk of disease this would not be identified prior to licensing. The aim of this study was to investigate the CD4 cell count and viral load-specific rates of fatal and nonfatal AIDS and non-AIDS events according to current antiretrovirals. Methods: Poisson regression was used to compare overall events (fatal or nonfatal AIDS, non-AIDS or death), AIDS events (fatal and nonfatal) or non-AIDS events (fatal or nonfatal) for specific nucleoside pairs and third drugs used with more than 1000 personyears of follow-up (PYFU) after 1 January 2001. Results: Nine thousand, eight hundred and one patients contributed 42372.5 PYFU, during which 1203 (437 AIDS and 766 non-AIDS) events occurred. After adjustment, there was weak evidence of a difference in the overall events rates between nucleoside pairs (global P-value1/40.084), and third drugs (global P-value1/40.031). As compared to zidovudine/lamivudine, patients taking abacavir/lamivudine [adjusted incidence rate ratio (aIRR) 1.22; 95% CI 0.99-1.49] and abacavir and 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 with those taking efavirenz (aIRR 1.46; 95% CI 1.09-1.95). Conclusion: There was little evidence of substantial differences between antiretrovirals in the incidence of clinical disease for a given CD4 cell count or viral load, suggesting there are unlikely to be major unidentified adverse effects of specific antiretrovirals. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Background: CD4 cell count 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 increase the risk of disease this would not be identified prior to licensing. The aim of this study was to investigate the CD4 cell count and viral load-specific rates of fatal and nonfatal AIDS and non-AIDS events according to current antiretrovirals. Methods: Poisson regression was used to compare overall events (fatal or nonfatal AIDS, non-AIDS or death), AIDS events (fatal and nonfatal) or non-AIDS events (fatal or nonfatal) for specific nucleoside pairs and third drugs used with more than 1000 personyears of follow-up (PYFU) after 1 January 2001. Results: Nine thousand, eight hundred and one patients contributed 42372.5 PYFU, during which 1203 (437 AIDS and 766 non-AIDS) events occurred. After adjustment, there was weak evidence of a difference in the overall events rates between nucleoside pairs (global P-value1/40.084), and third drugs (global P-value1/40.031). As compared to zidovudine/lamivudine, patients taking abacavir/lamivudine [adjusted incidence rate ratio (aIRR) 1.22; 95% CI 0.99-1.49] and abacavir and 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 with those taking efavirenz (aIRR 1.46; 95% CI 1.09-1.95). Conclusion: There was little evidence of substantial differences between antiretrovirals in the incidence of clinical disease for a given CD4 cell count or viral load, suggesting there are unlikely to be major unidentified adverse effects of specific antiretrovirals. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Background: A hepatitis C (HCV) cure is associated with changes in lipids and inflammatory biomarkers, but its impact on clinical endpoints among treated human immunodeficiency virus (HIV)/HCV coinfected persons is unclear. Methods: People living with HIV from EuroSIDA with a known HCV status after January 2001 were classified into strata based on time-updated HCV RNA measurements and HCV treatment, as either HCV antibody-negative; spontaneously resolved HCV; chronic, untreated HCV; cured HCV (HCV RNA-negative); or HCV treatment failures (HCV RNA-positive). Poisson regression was used to compare incidence rates between HCV groups for end-stage liver disease (ESLD; including hepatocellular carcinoma [HCC]), non-acquired immunodeficiency virus defining malignancy (NADM; excluding HCC), and cardiovascular disease (CVD). Results: There were 16 618 persons included (median follow-up 8.3 years, interquartile range 3.1-13.7). There were 887 CVD, 902 NADM, and 436 ESLD events; crude incidence rates/1000 person-years follow-up were 6.4 (95% confidence interval [CI] 6.0-6.9) for CVD, 6.5 (95% CI 6.1-6.9) for NADM, and 3.1 (95% CI 2.8-3.4) for ESLD. After adjustment, there were no differences in incidence rates of NADM or CVD across the 5 groups. HCV-negative individuals (adjusted incidence rate ratio [aIRR] 0.22, 95% CI 0.14-0.34) and those with spontaneous clearance (aIRR 0.61, 95% CI 0.36-1.02) had reduced rates of ESLD compared to cured individuals. Persons with chronic, untreated HCV infections (aIRR 1.47, 95% CI 1.02-2.13) or treatment failure (aIRR 1.80, 95% CI 1.22-2.66) had significantly raised rates of ESLD, compared to those who were cured. Conclusions: Incidences of NADM or CVD were independent of HCV group, whereas those cured had substantially lower incidences of ESLD, underlining he importance of successful HCV treatment for reducing ESLD. © 2019 The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.