Impact of hepatitis C virus antibody positivity on mortality and causes of death in people living with HIV in Georgia

Hepatitis C co-infection in people living with HIV (PLWH) is common in Georgia. Antiretroviral therapy (ART) is widely available in the country since 2004, and from 2011, patients have unlimited access to hepatitis C virus (HCV) treatment. A retrospective nationwide cohort study included adult PLWH diagnosed between 2004–2016, who were followed up until 31 December 2017. Predictors of mortality were assessed in Cox proportional hazards regression model. A total of 4560 persons contributed 22,322 person-years (PY) of follow-up, including 2058 (45.1%, 10,676 PY) anti-HCV+ patients. After the median 4.1 years of follow-up, 954 persons died, including 615 anti-HCV+ patients. Persons with HCV had higher overall mortality compared to HIV monoinfection (5.76/100 PY vs. 2.91/100 PY, p < 0.0001). In multivariable analysis, anti-HCV positivity was significantly associated with mortality (adjusted hazard ratio: 1.42, 95% CI: 1.09–1.85). Among anti-HCV+ persons, liver-related mortality due to viral hepatitis before the availability of HCV therapy (2004–2011) was 2.11 cases per 100 PY and this decreased to 0.79 cases per 100 PY after 2011 (p < 0.0001). AIDS remained the leading cause of death prior to and after 2011. Wide availability of ART and anti-HCV therapy translated into a significant decline in mortality including due to liver-related causes. Improving earlier diagnosis will decrease excess AIDS-related mortality among people living with HIV/HCV co-infection.

Download Full-text

Causes of death and associated factors over a decade of follow-up in a cohort of people living with HIV in rural Tanzania

BMC Infectious Diseases ◽

10.1186/s12879-021-06962-3 ◽

2022 ◽

Vol 22 (1) ◽

Author(s):

Getrud Joseph Mollel ◽

Lilian Moshi ◽

Hoda Hazem ◽

Anna Eichenberger ◽

Olivia Kitau ◽

...

Keyword(s):

Associated Factors ◽

Causes Of Death ◽

Proportional Hazards ◽

Cd4 Count ◽

People Living With Hiv ◽

Factors Associated ◽

Rural Tanzania ◽

Living With Hiv ◽

Related Mortality

Abstract Background Nearly half of HIV-related deaths occur in East and Southern Africa, yet data on causes of death (COD) are scarce. We determined COD and associated factors among people living with HIV (PLHIV) in rural Tanzania. Methods PLHIV attending the Chronic Diseases Clinic of Ifakara, Morogoro are invited to enrol in the Kilombero and Ulanga Antiretroviral Cohort (KIULARCO). Among adults (≥ 15 years) enrolled in 2005–2018, with follow-up through April 2019, we classified COD in comprehensive classes and as HIV- or non-HIV-related. In the subset of participants enrolled in 2013–2018 (when data were more complete), we assessed cause-specific mortality using cumulative incidences, and associated factors using proportional hazards models. Results Among 9871 adults (65% female, 26% CD4 count < 100 cells/mm3), 926 (9%) died, among whom COD were available for 474 (51%), with missing COD mainly in earlier years. The most common COD were tuberculosis (N = 127, 27%), non-AIDS-related infections (N = 72, 15%), and other AIDS-related infections (N = 59, 12%). Cardiovascular and renal deaths emerged as important COD in later calendar years, with 27% of deaths in 2018 attributable to cardiovascular causes. Most deaths (51%) occurred within the first six months following enrolment. Among 3956 participants enrolled in 2013–2018 (N = 203 deaths, 200 with COD ascertained), tuberculosis persisted as the most common COD (25%), but substantial proportions of deaths from six months after enrolment onwards were attributable to renal (14%), non-AIDS-related infections (13%), other AIDS-related infections (10%) and cardiovascular (10%) causes. Factors associated with higher HIV-related mortality were sex, younger age, living in Ifakara town, HIV status disclosure, hospitalisation, not being underweight, lower CD4 count, advanced WHO stage, and gaps in care. Factors associated with higher non-HIV-related mortality included not having an HIV-positive partner, lower CD4 count, advanced WHO stage, and gaps in care. Conclusion Incidence of HIV-related mortality was higher than that of non-HIV-related mortality, even in more recent years, likely due to late presentation. Tuberculosis was the leading specific COD identified, particularly soon after enrolment, while in later calendar years cardiovascular and renal causes emerged as important, emphasising the need for improved screening and management.

Download Full-text

The Efficacy of Etoposide-Based Therapy in Adult Secondary Hemophagocytic Lymphohistiocytosis

Acta Haematologica ◽

10.1159/000514920 ◽

2021 ◽

pp. 1-9

Author(s):

Leonard Naymagon ◽

Douglas Tremblay ◽

John Mascarenhas

Keyword(s):

Hemophagocytic Lymphohistiocytosis ◽

Proportional Hazards ◽

Multivariable Analysis ◽

Cox Proportional Hazards ◽

Rank Test ◽

Kaplan Meier ◽

Hazard Ratios ◽

Significant Difference ◽

The Impact

Data supporting the use of etoposide-based therapy in hemophagocytic lymphohistiocytosis (HLH) arise largely from pediatric studies. There is a lack of comparable data among adult patients with secondary HLH. We conducted a retrospective study to assess the impact of etoposide-based therapy on outcomes in adult secondary HLH. The primary outcome was overall survival. The log-rank test was used to compare Kaplan-Meier distributions of time-to-event outcomes. Multivariable Cox proportional hazards modeling was used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). Ninety adults with secondary HLH seen between January 1, 2009, and January 6, 2020, were included. Forty-two patients (47%) received etoposide-based therapy, while 48 (53%) received treatment only for their inciting proinflammatory condition. Thirty-three patients in the etoposide group (72%) and 32 in the no-etoposide group (67%) died during follow-up. Median survival in the etoposide and no-etoposide groups was 1.04 and 1.39 months, respectively. There was no significant difference in survival between the etoposide and no-etoposide groups (log-rank <i>p</i> = 0.4146). On multivariable analysis, there was no association between treatment with etoposide and survival (HR for death with etoposide = 1.067, 95% CI: 0.633–1.799, <i>p</i> = 0.8084). Use of etoposide-based therapy was not associated with improvement in outcomes in this large cohort of adult secondary HLH patients.

Download Full-text

1036. Persistence of Guideline-Recommended Antiretroviral Therapy Regimens among Persons Living with HIV Newly Initiating Treatment in the US

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1222 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S548-S549

Author(s):

Joshua P Cohen ◽

Xingzhi Wang ◽

Rolin L Wade ◽

Helena Diaz Cuervo ◽

Dionne M Dionne

Keyword(s):

Antiretroviral Therapy ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Treatment Discontinuation ◽

Forest Plot ◽

Current Guideline ◽

First Line ◽

Persons Living With Hiv ◽

Living With Hiv

Abstract Background Discontinuation of first-line antiretroviral therapy (ART) may lead to poor outcomes for persons living with HIV (PLWH). While single-tablet regimens (STRs) have been associated with greater persistence compared to multi-tablet regimens (MTRs), few real-world studies have assessed persistence with current guideline-recommended ART regimens. The study aims to assess persistence among treatment-naïve PLWH initiating guideline-recommended ART regimens Methods Longitudinal pharmacy claims were extracted from IQVIA’s US LRx database for PLWH initiating ART between Jan 1, 2016 - Jul 31, 2019 (index period), with the observational period up to Jan 31, 2020. Index date was defined as the date of the first ART claim for STRs, or the date of the last filled drug of 1st set of claims for MTRs. Persistence was measured as the number of days until treatment discontinuation (≥ 90-day gap in therapy) and presented via Kaplan-Meier curves. Risk of discontinuation was assessed via Cox proportional hazards models, with BIC/FTC/TAF used as the reference ART regimen. Results Overall, 90,949 PLWH initiated STRs and 20,737 initiated MTRs. Average (SD) age was 43 (14) years, 75% were male, and 75% had commercial insurance. At 6 months of follow-up, 71% of PLWH initiating STRs and 56% initiating MTRs remained on their ART regimen. The proportion remaining on their index regimen at 6 months of follow-up was 79% for BIC/FTC/TAF, 73% for EVG/COBI/FTC/TAF, 71% for DTG/ABC/3TC, 69% for DTG + FTC/TAF, 67% for EFV/FTC/TDF, 62% for EVG/COBI/FTC/TDF, and 38% for DTG + FTC/TDF. Risk of discontinuation was higher for MTRs compared to STRs (hazard ratio [HR]: 1.63, 95% CI: 1.61 - 1.66). Compared to the referent BIC/FTC/TAF, risk of discontinuation was higher for EVG/COBI/FTC/TAF (HR: 1.54, 95% CI: 1.48 - 1.60), DTG/ABC/3TC (HR: 1.58, 95% CI: 1.52, 1.65), DTG + FTC/TAF (HR: 1.83, 95% CI: 1.74 - 1.93), EFV/FTC/TDF (HR: 2.31, 95% CI: 2.21 - 2.41), EVG/COBI/FTC/TDF (HR: 2.58, 95% CI: 2.47 - 2.70), and DTG + FTC/TDF (HR: 6.20, 95% CI: 5.83 - 6.59). Table 1. Persistence with ART by regimen for STR and MTR Figure 1. Forest Plot of Hazard Ratios for Treatment Discontinuation Conclusion Among US adult PLWH, STRs were associated with longer persistence on first-line therapy compared to MTRs. Among STRs, persistence was highest for BIC/FTC/TAF. Disclosures All Authors: No reported disclosures

Download Full-text

Cystatin C and Urine Albumin to Creatinine Ratio Predict 5-Year Mortality and Cardiovascular Events in People Living With HIV

The Journal of Infectious Diseases ◽

10.1093/infdis/jiaa433 ◽

2020 ◽

Author(s):

Robin Chazot ◽

Elisabeth Botelho-Nevers ◽

Christophe Mariat ◽

Anne Frésard ◽

Etienne Cavalier ◽

...

Keyword(s):

Cystatin C ◽

Cardiovascular Events ◽

Multivariable Analysis ◽

Receiver Operating Curve ◽

People Living With Hiv ◽

Creatinine Ratio ◽

Urine Albumin ◽

All Cause Mortality ◽

Living With Hiv

Abstract Background Identifying people with HIV (PWH) at risk for chronic kidney disease, cardiovascular events, and death is crucial. We evaluated biomarkers to predict all-cause mortality and cardiovascular events, and measured glomerular filtration rate (mGFR) slope. Methods Biomarkers were measured at enrollment. Baseline and 5-year mGFR were measured by plasma iohexol clearance. Outcomes were a composite criterion of all-cause mortality and/or cardiovascular events, and mGFR slope. Results Of 168 subjects, 146 (87.4%) had undetectable HIV load. Median follow-up was 59.1 months (interquartile range, 56.2–62.1). At baseline, mean age was 49.5 years (± 9.8) and mean mGFR 98.9 mL/min/1.73m2 (± 20.6). Seventeen deaths and 10 cardiovascular events occurred during 5-year follow-up. Baseline mGFR was not associated with mortality/cardiovascular events. In multivariable analysis, cystatin C (hazard ratio [HR], 5.978; 95% confidence interval [CI], 2.774–12.88; P < .0001) and urine albumin to creatinine ratio (uACR) at inclusion (HR, 1.002; 95% CI, 1.001–1.004; P < .001) were associated with mortality/cardiovascular events. Area under receiver operating curve of cystatin C was 0.67 (95% CI, .55–.79) for mortality/cardiovascular event prediction. Biomarkers were not associated with GFR slope. Conclusions uACR and cystatin C predict all-cause mortality and/or cardiovascular events in PWH independently of mGFR.

Download Full-text

Hepatitis C virus or hepatitis B virus coinfection and lymphoma risk in people living with HIV

AIDS ◽

10.1097/qad.0000000000002461 ◽

2020 ◽

Vol 34 (4) ◽

pp. 599-608 ◽

Cited By ~ 1

Author(s):

Caroline Besson ◽

Nicolas Noel ◽

Remi Lancar ◽

Sophie Prevot ◽

Michele Algarte-Genin ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Hepatitis B Virus ◽

Hepatitis B ◽

People Living With Hiv ◽

B Virus ◽

Living With Hiv ◽

Lymphoma Risk

Download Full-text

Low hepatitis C virus reinfection rate despite ongoing risk following universal access to direct-acting antiviral therapy among people living with HIV

AIDS ◽

10.1097/qad.0000000000002562 ◽

2020 ◽

Vol 34 (9) ◽

pp. 1347-1358

Author(s):

Samira Hosseini-Hooshyar ◽

Marianne Martinello ◽

Jasmine Yee ◽

Phillip Read ◽

David Baker ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Antiviral Therapy ◽

Universal Access ◽

People Living With Hiv ◽

Reinfection Rate ◽

Direct Acting Antiviral ◽

Direct Acting ◽

Living With Hiv

Download Full-text

The role of barriers to care on the propensity for hepatitis C virus nonreferral among people living with HIV

AIDS ◽

10.1097/qad.0000000000002610 ◽

2020 ◽

Vol 34 (11) ◽

pp. 1681-1683

Author(s):

Edward R. Cachay ◽

Francesca J. Torriani ◽

Lucas Hill ◽

Sonia Jain ◽

Azucena Del Real ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Barriers To Care ◽

People Living With Hiv ◽

Living With Hiv

Download Full-text

Failure to reach uric acid target of <0.36 mmol/L in hyperuricaemia of gout is associated with elevated total and cardiovascular mortality

RMD Open ◽

10.1136/rmdopen-2019-001015 ◽

2019 ◽

Vol 5 (2) ◽

pp. e001015 ◽

Cited By ~ 10

Author(s):

Fernando Pérez Ruiz ◽

Pascal Richette ◽

Austin G Stack ◽

Ravichandra Karra Gurunath ◽

Ma Jesus García de Yébenes ◽

...

Keyword(s):

Uric Acid ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

First Year ◽

Cox Proportional Hazards Models ◽

Crude Mortality ◽

Risk Patients ◽

The Impact ◽

Related Mortality

ObjectiveTo determine the impact of achieving serum uric acid (sUA) of <0.36 mmol/L on overall and cardiovascular (CV) mortality in patients with gout.MethodsProspective cohort of patients with gout recruited from 1992 to 2017. Exposure was defined as the average sUA recorded during the first year of follow-up, dichotomised as ≤ or >0.36 mmol/L. Bivariate and multivariate Cox proportional hazards models were used to determine mortality risks, expressed HRs and 95% CIs.ResultsOf 1193 patients, 92% were men with a mean age of 60 years, 6.8 years’ disease duration, an average of three to four flares in the previous year, a mean sUA of 9.1 mg/dL at baseline and a mean follow-up 48 months; and 158 died. Crude mortality rates were significantly higher for an sUA of ≥0.36 mmol/L, 80.9 per 1000 patient-years (95% CI 59.4 to 110.3), than for an sUA of <0.36 mmol/L, 25.7 per 1000 patient-years (95% CI 21.3 to 30.9). After adjustment for age, sex, CV risk factors, previous CV events, observation period and baseline sUA concentration, an sUA of ≥0.36 mmol/L was associated with elevated overall mortality (HR=2.33, 95% CI 1.60 to 3.41) and CV mortality (HR=2.05, 95% CI 1.21 to 3.45).ConclusionsFailure to reach a target sUA level of 0.36 mmol/L in patients with hyperuricaemia of gout is an independent predictor of overall and CV-related mortality. Targeting sUA levels of <0.36 mmol/L should be a principal goal in these high-risk patients in order to reduce CV events and to extend patient survival.

Download Full-text

Association between chronic hepatitis C virus infection and myocardial infarction in people living with HIV in the United States

10.1101/453860 ◽

2018 ◽

Author(s):

Jessica Williams-Nguyen ◽

Stephen E Hawes ◽

Robin M Nance ◽

Sara Lindström ◽

Susan R Heckbert ◽

...

Keyword(s):

Myocardial Infarction ◽

Hepatitis C Virus ◽

Hepatitis C ◽

The United States ◽

Hcv Rna ◽

High Risk Population ◽

People Living With Hiv ◽

Extrahepatic Manifestations ◽

Chronic Hcv ◽

Living With Hiv

AbstractHepatitis C virus (HCV) is common among people living with HIV (PLWH). The potential for extrahepatic manifestations of HCV, including myocardial infarction (MI), is a topic of active research. MI is classified into types, predominantly atheroembolic Type 1 MI (T1MI) and supply-demand mismatch Type 2 MI (T2MI). We examined the association between HCV and MI in the CFAR Network of Integrated Clinical Systems (CNICS), a multi-center clinical cohort of PLWH. MIs were centrally adjudicated and categorized by type using the Universal MI definition. We estimated the association between chronic HCV (RNA+) and time to MI adjusting for demographic characteristics, cardiovascular risk factors, clinical characteristics and substance use. Among 24,755 PLWH aged ≥18, there were 336 T1MI and 330 T2MI during a median of 4.2 years of follow-up. HCV was associated with a 68% greater risk of T2MI (adjusted hazard ratio (aHR) 1.68, 95% CI: 1.22, 2.30) but not T1MI (aHR 0.96, 95% CI: 0.63, 1.45). In a cause-specific analysis of T2MI, HCV was associated with a 2-fold greater risk of T2MI attributed to sepsis (aHR 2.26, 95% CI: 1.34, 3.81). Extrahepatic manifestations of HCV in this high-risk population are an important area for continued research.

Download Full-text

Sex differences in the 10-year survival of patients undergoing maintenance hemodialysis in the Q-Cohort Study

Scientific Reports ◽

10.1038/s41598-021-03551-x ◽

2022 ◽

Vol 12 (1) ◽

Author(s):

Hiroaki Tsujikawa ◽

Shunsuke Yamada ◽

Hiroto Hiyamuta ◽

Masatomo Taniguchi ◽

Kazuhiko Tsuruya ◽

...

Keyword(s):

Proportional Hazards ◽

Japanese Patients ◽

Hemodialysis Patients ◽

Cox Proportional Hazards ◽

Maintenance Hemodialysis ◽

Cox Proportional Hazards Models ◽

Hazard Ratios ◽

Risk Of Mortality ◽

Related Mortality

AbstractWomen have a longer life expectancy than men in the general population. However, it has remained unclear whether this advantage is maintained in patients undergoing maintenance hemodialysis. The aim of this study was to compare the risk of mortality, especially infection-related mortality, between male and female hemodialysis patients. A total of 3065 Japanese hemodialysis patients aged ≥ 18 years old were followed up for 10 years. The primary outcomes were all-cause and infection-related mortality. The associations between sex and these outcomes were examined using Cox proportional hazards models. During the median follow-up of 8.8 years, 1498 patients died of any cause, 387 of whom died of infection. Compared with men, the multivariable-adjusted hazard ratios (95% confidence interval) for all-cause and infection-related mortality in women were 0.51 (0.45–0.58, P < 0.05) and 0.36 (0.27–0.47, P < 0.05), respectively. These findings remained significant even when propensity score-matching or inverse probability of treatment weighting adjustment methods were employed. Furthermore, even when the non-infection-related mortality was considered a competing risk, the infection-related mortality rate in women was still significantly lower than that in men. Regarding all-cause and infection-related deaths, women have a survival advantage compared with men among Japanese patients undergoing maintenance hemodialysis.

Download Full-text