Browsing by Author "Mocroft, Amanda (7006513758)"

Objectives: To describe changes in the prevalence of comorbidities and risk factors among HIV-positive individuals in the EuroSIDA study. Design: Comparison of two cross-sectional cohorts of HIV-positive adults under active follow-up in 2006 and 2014. Methods: Baseline demographics and prevalence of comorbidities were described. Factors associated with the prevalence of chronic kidney disease (CKD) and cardiovascular disease (CVD) were assessed by logistic regression modelling using generalized estimating equations. Results: Nine thousand, seven hundred and ninety-eight individuals were under active follow-up in EuroSIDA during 2006 and 12 882 during 2014. Compared with study participants in 2006, those in 2014 were older [median age 48.6 years (IQR 40.3 55.1) vs. 43.1 years (37.2 50.0) in 2006] and had higher prevalence of hypertension (59.6 vs. 47% in 2006), diabetes (6.3 vs. 5.4%), CKD (6.9 vs. 4.1%) and CVD (5.0 vs. 3.7%). Individuals in the 2014 cohort had higher odds for CKD (unadjusted OR 2.62, 95% CI 2.30 2.99, P0.0001) and CVD (OR 1.88, CI 1.68 2.10, P0.0001), but after multivariable adjustment for age group, comorbidities and other factors, year of cohort was no longer significantly associated with the odds of CKD [adjusted OR (aOR) 0.97, CI 0.52 1.82, P 0.92) or of CVD (aOR 0.94, CI 0.54 1.63, P 0.82). aCentre for Clinica Conclusion: Between 2006 and 2014, the population aged and experienced an overall higher prevalence of non-AIDS comorbidities, including CKD and CVD. The increase in CVD could be explained by the aging population, and the increase in CKD by aging and changes in other factors. Treatment strategies balancing HIV outcomes with long-Term management of comorbidities remain a priority. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

Objectives: To describe changes in the prevalence of comorbidities and risk factors among HIV-positive individuals in the EuroSIDA study. Design: Comparison of two cross-sectional cohorts of HIV-positive adults under active follow-up in 2006 and 2014. Methods: Baseline demographics and prevalence of comorbidities were described. Factors associated with the prevalence of chronic kidney disease (CKD) and cardiovascular disease (CVD) were assessed by logistic regression modelling using generalized estimating equations. Results: Nine thousand, seven hundred and ninety-eight individuals were under active follow-up in EuroSIDA during 2006 and 12 882 during 2014. Compared with study participants in 2006, those in 2014 were older [median age 48.6 years (IQR 40.3 55.1) vs. 43.1 years (37.2 50.0) in 2006] and had higher prevalence of hypertension (59.6 vs. 47% in 2006), diabetes (6.3 vs. 5.4%), CKD (6.9 vs. 4.1%) and CVD (5.0 vs. 3.7%). Individuals in the 2014 cohort had higher odds for CKD (unadjusted OR 2.62, 95% CI 2.30 2.99, P0.0001) and CVD (OR 1.88, CI 1.68 2.10, P0.0001), but after multivariable adjustment for age group, comorbidities and other factors, year of cohort was no longer significantly associated with the odds of CKD [adjusted OR (aOR) 0.97, CI 0.52 1.82, P 0.92) or of CVD (aOR 0.94, CI 0.54 1.63, P 0.82). aCentre for Clinica Conclusion: Between 2006 and 2014, the population aged and experienced an overall higher prevalence of non-AIDS comorbidities, including CKD and CVD. The increase in CVD could be explained by the aging population, and the increase in CKD by aging and changes in other factors. Treatment strategies balancing HIV outcomes with long-Term management of comorbidities remain a priority. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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.

Background: Weight gain effects of individual antiretroviral drugs are not fully understood. We investigated associations between a prespecified clinically significant increase (>7%) in body-mass index (BMI) and contemporary antiretroviral use. Methods: The International Cohort Consortium of Infectious Diseases (RESPOND) is a prospective, multicohort collaboration, including data from 17 well established cohorts and over 29 000 people living with HIV. People with HIV under prospective follow-up from Jan 1, 2012, and older than 18 years were eligible for inclusion. Each cohort contributed a predefined minimum number of participants related to the size of the specific cohort (with a minimum of 1000 participants). Participants were required to have CD4 cell counts and HIV viral load measurement in the 12 months before or within 3 months after baseline. For all antiretroviral drugs received at or after RESPOND entry, changes from pre-antiretroviral BMI levels (baseline) were considered at each BMI measurement during antiretroviral treatment. We used logistic regression to identify individual antiretrovirals that were associated with first occurrence of a more than 7% increase in BMI from pre-antiretroviral BMI. We adjusted analyses for time on antiretrovirals, pre-antiretroviral BMI, demographics, geographical region, CD4 cell count, viral load, smoking status, and AIDS at baseline. Results: 14 703 people were included in this study, of whom 7863 (53·5%) had a more than 7% increase in BMI. Compared with lamivudine, use of dolutegravir (odds ratio [OR] 1·27, 95% CI 1·17–1·38), raltegravir (1·37, 1·20–1·56), and tenofovir alafenamide (1·38, 1·22–1·35) was significantly associated with a more than 7% BMI increase, as was low pre-antiretroviral BMI (2·10, 1·91–2·31 for underweight vs healthy weight) and Black ethnicity (1·61, 1·47–1·76 vs White ethnicity). Higher CD4 count was associated with a reduced risk of BMI increase (0·97, 0·96–0·98 per 100 cells per μL increase). Relative to lamivudine, dolutegravir without tenofovir alafenamide (OR 1·21, 95% CI 1·19–1·32) and tenofovir alafenamide without dolutegravir (1·33, 1·15–1·53) remained independently associated with a more than 7% increase in BMI; the associations were higher when dolutegravir and tenofovir alafenamide were used concomitantly (1·79, 1·52–2·11, and 1·70, 1·44–2·01, respectively). Interpretation: Clinicians and people with HIV should be aware of associations between weight gain and use of dolutegravir, tenofovir alafenamide, and raltegravir, particularly given the potential consequences of weight gain, such as insulin resistance, dyslipidaemia, and hypertension. Funding: The CHU St Pierre Brussels HIV Cohort, The Austrian HIV Cohort Study, The Australian HIV Observational Database, The AIDS Therapy Evaluation in the Netherlands national observational HIV cohort, The EuroSIDA cohort, The Frankfurt HIV Cohort Study, The Georgian National AIDS Health Information System, The Nice HIV Cohort, The ICONA Foundation, The Modena HIV Cohort, The PISCIS Cohort Study, The Swiss HIV Cohort Study, The Swedish InfCare HIV Cohort, The Royal Free HIV Cohort Study, The San Raffaele Scientific Institute, The University Hospital Bonn HIV Cohort and The University of Cologne HIV Cohorts, ViiV Healthcare, and Gilead Sciences. © 2021 Elsevier Ltd

Background: Weight gain effects of individual antiretroviral drugs are not fully understood. We investigated associations between a prespecified clinically significant increase (>7%) in body-mass index (BMI) and contemporary antiretroviral use. Methods: The International Cohort Consortium of Infectious Diseases (RESPOND) is a prospective, multicohort collaboration, including data from 17 well established cohorts and over 29 000 people living with HIV. People with HIV under prospective follow-up from Jan 1, 2012, and older than 18 years were eligible for inclusion. Each cohort contributed a predefined minimum number of participants related to the size of the specific cohort (with a minimum of 1000 participants). Participants were required to have CD4 cell counts and HIV viral load measurement in the 12 months before or within 3 months after baseline. For all antiretroviral drugs received at or after RESPOND entry, changes from pre-antiretroviral BMI levels (baseline) were considered at each BMI measurement during antiretroviral treatment. We used logistic regression to identify individual antiretrovirals that were associated with first occurrence of a more than 7% increase in BMI from pre-antiretroviral BMI. We adjusted analyses for time on antiretrovirals, pre-antiretroviral BMI, demographics, geographical region, CD4 cell count, viral load, smoking status, and AIDS at baseline. Results: 14 703 people were included in this study, of whom 7863 (53·5%) had a more than 7% increase in BMI. Compared with lamivudine, use of dolutegravir (odds ratio [OR] 1·27, 95% CI 1·17–1·38), raltegravir (1·37, 1·20–1·56), and tenofovir alafenamide (1·38, 1·22–1·35) was significantly associated with a more than 7% BMI increase, as was low pre-antiretroviral BMI (2·10, 1·91–2·31 for underweight vs healthy weight) and Black ethnicity (1·61, 1·47–1·76 vs White ethnicity). Higher CD4 count was associated with a reduced risk of BMI increase (0·97, 0·96–0·98 per 100 cells per μL increase). Relative to lamivudine, dolutegravir without tenofovir alafenamide (OR 1·21, 95% CI 1·19–1·32) and tenofovir alafenamide without dolutegravir (1·33, 1·15–1·53) remained independently associated with a more than 7% increase in BMI; the associations were higher when dolutegravir and tenofovir alafenamide were used concomitantly (1·79, 1·52–2·11, and 1·70, 1·44–2·01, respectively). Interpretation: Clinicians and people with HIV should be aware of associations between weight gain and use of dolutegravir, tenofovir alafenamide, and raltegravir, particularly given the potential consequences of weight gain, such as insulin resistance, dyslipidaemia, and hypertension. Funding: The CHU St Pierre Brussels HIV Cohort, The Austrian HIV Cohort Study, The Australian HIV Observational Database, The AIDS Therapy Evaluation in the Netherlands national observational HIV cohort, The EuroSIDA cohort, The Frankfurt HIV Cohort Study, The Georgian National AIDS Health Information System, The Nice HIV Cohort, The ICONA Foundation, The Modena HIV Cohort, The PISCIS Cohort Study, The Swiss HIV Cohort Study, The Swedish InfCare HIV Cohort, The Royal Free HIV Cohort Study, The San Raffaele Scientific Institute, The University Hospital Bonn HIV Cohort and The University of Cologne HIV Cohorts, ViiV Healthcare, and Gilead Sciences. © 2021 Elsevier Ltd

Objectives: Although direct-acting antivirals (DAAs) can clear HCV in nearly all HIV/HCV-coinfected individuals, high rates of reinfection may hamper efforts to eliminate HCV in this population. We investigated reinfection after sustained virological response (SVR) in HIV/HCV-coinfected individuals in Europe. Methods: Factors associated with odds of reinfection by 2 years after SVR in EuroSIDA participants with one or more HCV-RNA test and 2 years follow-up were assessed using logistic regression. Results: Overall, 1022 individuals were included. The median age was 50 (interquartile range: 43–54 years), and most were male (78%), injection drug users (52%), and received interferon (IFN)-free DAAs (62%). By 24 months, 75 [7.3%, 95% confidence interval (CI): 5.7–8.9%] individuals were reinfected. Among individuals treated prior to 2014, 16.1% were reinfected compared with 4.2% and 8.3%, respectively, among those treated during or after 2014 with IFN-free and IFN-based therapy. After adjustment, individuals who had started treatment during or after 2014 with IFN-free or IFN-based therapy had significantly lower odds of reinfection (adjusted odds ratio = 0.21, 95% CI: 0.11–0.38; 0.43, 95% CI: 0.22–0.83) compared with those who had received therapy before 2014. There were no significant differences in odds of reinfection according to age, gender, European region, HIV transmission risk group or liver fibrosis. Conclusions: Among HIV/HCV-coinfected individuals in Europe, 7.3% were reinfected with HCV within 24 months of achieving SVR, with evidence suggesting that this is decreasing over time and with use of newer HCV regimens. Harm reduction to reduce reinfection and surveillance to detect early reinfection with an offer of treatment are essential to eliminate HCV. © 2021 British HIV Association.

Background:Hepatitis C virus (HCV) infection has been associated with increased risk of chronic kidney disease (CKD). We investigated the impact of HCV cure on CKD in HIV-positive persons in the EuroSIDA study.Methods:HIV-positive persons with known HCV status and at least three serum creatinine measurements after 1/1/2004 were compared based on time-updated HCV-RNA and HCV treatment: anti-HCV-negative, spontaneously cleared HCV, chronic untreated HCV, successfully treated HCV, and HCV-RNA positive after HCV treatment. Poisson regression compared incidence rates of CKD [confirmed (>3 months apart) eGFR <60 ml/min per 1.73 m2] between HCV strata.Results:Fourteen thousand, seven hundred and fifty-four persons were included; at baseline 9273 (62.9%) were HCV-Ab negative, 696 (4.7%) spontaneous clearers, 3021 (20.5%) chronically infected, 922 (6.2%) successfully treated and 842 (5.7%) HCV-RNA positive after treatment. During 115 335 person-years of follow-up (PYFU), 1128 (7.6%) developed CKD; crude incidence 9.8/1000 PYFU (95% CI 9.2-10.4). After adjustment, persons anti-HCV negative [adjusted incidence rate ratio (aIRR) 0.59; 95% CI 0.46-0.75] and spontaneous clearers (aIRR 0.67; 95% CI 0.47-0.97) had significantly lower rates of CKD compared with those cured whereas persons chronically infected (aIRR 0.85; 95% CI 0.65-1.12) and HCV-RNA positive after treatment (aIRR 0.71; 95% CI 0.49-1.04) had similar rates. Analysis in those without F3/F4 liver fibrosis using a more rigorous definition of CKD showed similar results.Conclusion:This large study found no evidence that successful HCV treatment reduced CKD incidence. Confounding by indication, where those with highest risk of CKD were prioritized for HCV treatment in the DAA era, may contribute to these findings. © 2020 Lippincott Williams and Wilkins. All rights reserved.

Background:Hepatitis C virus (HCV) infection has been associated with increased risk of chronic kidney disease (CKD). We investigated the impact of HCV cure on CKD in HIV-positive persons in the EuroSIDA study.Methods:HIV-positive persons with known HCV status and at least three serum creatinine measurements after 1/1/2004 were compared based on time-updated HCV-RNA and HCV treatment: anti-HCV-negative, spontaneously cleared HCV, chronic untreated HCV, successfully treated HCV, and HCV-RNA positive after HCV treatment. Poisson regression compared incidence rates of CKD [confirmed (>3 months apart) eGFR <60 ml/min per 1.73 m2] between HCV strata.Results:Fourteen thousand, seven hundred and fifty-four persons were included; at baseline 9273 (62.9%) were HCV-Ab negative, 696 (4.7%) spontaneous clearers, 3021 (20.5%) chronically infected, 922 (6.2%) successfully treated and 842 (5.7%) HCV-RNA positive after treatment. During 115 335 person-years of follow-up (PYFU), 1128 (7.6%) developed CKD; crude incidence 9.8/1000 PYFU (95% CI 9.2-10.4). After adjustment, persons anti-HCV negative [adjusted incidence rate ratio (aIRR) 0.59; 95% CI 0.46-0.75] and spontaneous clearers (aIRR 0.67; 95% CI 0.47-0.97) had significantly lower rates of CKD compared with those cured whereas persons chronically infected (aIRR 0.85; 95% CI 0.65-1.12) and HCV-RNA positive after treatment (aIRR 0.71; 95% CI 0.49-1.04) had similar rates. Analysis in those without F3/F4 liver fibrosis using a more rigorous definition of CKD showed similar results.Conclusion:This large study found no evidence that successful HCV treatment reduced CKD incidence. Confounding by indication, where those with highest risk of CKD were prioritized for HCV treatment in the DAA era, may contribute to these findings. © 2020 Lippincott Williams and Wilkins. All rights reserved.