OBJECTIVES:Although several antiretroviral drugs, including the d-drugs stavudine (d4T) and didanosine (ddI), may cause biomarker-defined hepatotoxicity, their association with clinically defined ...end-stage liver disease (ESLD) and hepatocellular carcinoma (HCC) remains unknown.
DESIGN:Prospective cohort study.
METHODS:Data collection on adverse events of anti-HIV drugs study (D:A:D) participants were followed until the first of ESLD (variceal bleeding, hepatic encephalopathy, hepatorenal syndrome or liver transplantation), HCC (histology or α-fetoprotein along with imaging), death, 6 months after last visit or 1 February 2014. Associations between ESLD/HCC and cumulative use of individual antiretrovirals were investigated using Poisson regression adjusting for potential confounders.
RESULTS:During a median follow-up of 8.4 years, 319 ESLD/HCC cases occurred incidence 1.01/1000 person-years (95% confidence interval 0.90–1.12) with a 1-year mortality rate of 62.6%. After adjustment, cumulative (per 5 years) exposure to d4T relative rate 1.46 (95% confidence interval 1.20–1.77), ddI 1.32 (1.07–1.63), tenofovir TDF, 1.46 (1.11–1.93) and (fos)amprenavir APV; 1.47 (1.01–2.15) was associated with increased ESLD/HCC rates. Longer exposure to emtricitabine 0.51 (0.32–0.83) and nevirapine 0.76 (0.58–0.98) were associated with lower ESLD/HCC rates. The ddI/d4T-associated increased ESLD/HCC rate only started to decline 6 years after cessation.
CONCLUSION:Cumulative use of d4T, ddI, TDF and APV were independently associated with increased ESLD/HCC rates, and intensified monitoring of liver function should hence be considered among all individuals exposed for longer time periods. The use of d-drugs should furthermore be avoided, where there are alternatives available, and focus should be put on those with longer-term d-drugs exposure who remain at increased ESLD/HCC risk. The unexpected, and viral hepatitis-independent, TDF association calls for further investigations.
We screened 735 HIV-infected patients in Switzerland with unexplained alanine aminotransferase elevation for hepatitis E virus (HEV) immunoglobulin G. Although HEV seroprevalence in this population ...is low (2.6%), HEV RNA can persist in patients with low CD4 cell counts. Findings suggest chronic HEV infection should be considered as a cause of persistent alanine aminotransferase elevation.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background. Liver diseases are the leading causes of death in human immunodeficiency virus (HIV)—positive persons since the widespread use of combination antiretroviral treatment (cART). Most of ...these deaths are due to hepatitis C (HCV) or B (HBV) virus coinfections. Little is known about other causes. Prolonged exposure to some antiretroviral drugs might increase hepatic mortality. Methods. All patients in the Data Collection on Adverse Events of Anti-HIV Drugs study without HCV or HBV coinfection were prospectively followed from date of entry until death or last follow-up. In patients with liver-related death, clinical charts were reviewed using a structured questionnaire. Results. We followed 22 910 participants without hepatitis virus coinfection for 114 478 person-years. There were 12 liver-related deaths (incidence, 0.10/1000 person-years); 7 due to severe alcohol use and 5 due to established ART-related toxicity. The rate of ART-related deaths in treatment-experienced persons was 0.04/1000 person-years (95% confidence interval, .01, .10). Conclusions. We found a low incidence of liver-related deaths in HIV-infected persons without HCV or HBV coinfection. Liver-related mortality because of ART-related toxicity was rare.
Full text
Available for:
BFBNIB, NUK, PNG, UL, UM, UPUK
Highlights • This was a cross-sectional study of HIV-infected, antiretroviral therapy-naïve adults in Zambia and Switzerland. • HIV/hepatitis B virus (HBV) co-infected patients are at least three ...times more likely to have significant liver fibrosis compared to HIV monoinfected individuals. • The association between HBV and liver fibrosis seems to be driven by HBV viral load. • The main risk factors for liver fibrosis are similar in Switzerland and Zambia.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The Zurich Primary HIV Infection (ZPHI) study is a longitudinal cohort study established in 2002, aiming to study the clinical, epidemiological, and biological characteristics of primary HIV ...infection. The ZPHI enrolls individuals with documented primary HIV-1 infection. At the baseline and thereafter, the socio-demographic, clinical, and laboratory data are systematically collected, and regular blood sampling is performed for biobanking. By the end of December 2022, 486 people were enrolled, of which 353 were still undergoing active follow-up. Of the 486 participants, 86% had an acute infection, and 14% a recent HIV-1 infection. Men who have sex with men accounted for 74% of the study population. The median time from the estimated date of infection to diagnosis was 32 days. The median time from diagnosis to the initiation of antiretroviral therapy was 11 days, and this has consistently decreased over the last two decades. During the seroconversion phase, 447 (92%) patients reported having symptoms, of which only 73% of the patients were classified as having typical acute retroviral syndrome. The ZPHI study is a well-characterized cohort belonging to the most extensively studied primary HIV infection cohort. Its findings contribute to advancing our understanding of the early stages of HIV infection and pathogenesis, and it is paving the way to further improve HIV translational research and HIV medicine.
In many, but not all studies, people living with HIV (PLWH) have an increased risk of coronary artery disease (CAD) events compared to the general population. This has generated considerable interest ...in the early, non-invasive detection of asymptomatic (subclinical) atherosclerosis in PLWH. Ultrasound studies assessing carotid artery intima-media thickness (CIMT) have tended to show a somewhat greater thickness in HIV+ compared to HIV-, likely due to an increased prevalence of cardiovascular (CV) risk factors in PLWH. Coronary artery calcification (CAC) determination by non-contrast computed tomography (CT) seems promising to predict CV events but is limited to the detection of calcified plaque. Coronary CT angiography (CCTA) detects calcified and non-calcified plaque and predicts CAD better than either CAC or CIMT. A normal CCTA predicts survival free of CV events over a very long time-span. Research imaging techniques, including black-blood magnetic resonance imaging of the vessel wall and 18F-fluorodeoxyglucose positron emission tomography for the assessment of arterial inflammation have provided insights into the prevalence of HIV-vasculopathy and associated risk factors, but their clinical applicability remains limited. Therefore, CCTA currently appears as the most promising cardiac imaging modality in PLWH for the evaluation of suspected CAD, particularly in patients <50 years, in whom most atherosclerotic coronary lesions are non-calcified.
Hypertension is a stronger predictor of hemorrhagic than ischemic strokes in the general population. We aimed to identify whether hypertension or other risk factors, including HIV-related factors, ...differ in their associations with stroke subtypes in people living with HIV (PLWHIV).
HIV-1-positive individuals from the Data collection on Adverse events of anti-HIV Drugs (D:A:D) study were followed from the time of first blood pressure (BP) measurement after 1/1/1999 or study entry until the first of a validated stroke, 6 months after last follow-up or 1/2/2014. Stroke events were centrally validated using standardized criteria. Hypertension was defined as one systolic BP ≥ 140 mm Hg and/or diastolic BP ≥ 90 mm Hg. Poisson and Cox proportional hazards regression models determined associations of established cerebro/cardiovascular disease and HIV-related risk factors with stroke and tested whether these differed by stroke subtype.
590 strokes (83 hemorrhagic, 296 ischemic, 211 unknown) occurred over 339,979 person-years (PYRS) (incidence rate/1000 PYRS 1.74 95% confidence interval (CI) 1.60-1.88). Common predictors of both hemorrhagic and ischemic strokes were hypertension (relative hazard 3.55 95% CI 2.29-5.50 and 2.24 1.77-2.84 respectively) and older age (1.28 1.17-1.39 and 1.19 1.12-1.25). Male gender (1.62 1.14-2.31 and 0.60 0.35-0.91), previous cardiovascular events (4.03 2.91-5.57 and 1.44 0.66-3.16) and smoking (1.90 1.41-2.56 and 1.08 0.68-1.71) were stronger predictors of ischemic then hemorrhagic strokes, whereas hypertension, hepatitis C (1.32 0.72-2.40 and 0.46 0.30-0.70) and estimated glomerular filtration rate < 60 mL/min/1.72 m
(4.80 2.47-9.36 and 1.04 0.67-1.60) were stronger predictors of hemorrhagic than ischemic strokes. A CD4 count < 200 cells/μL was associated with an increased risk of hemorrhagic stroke only.
Risk factors for stroke may differ by subtype in PLWHIV, emphasizing the importance of further research to increase the precision of stroke risk estimation.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Ribavirin (RBV) is an essential component of most current hepatitis C (HCV) treatment regimens and still standard of care in the combination with pegylated interferon (pegIFN) to treat chronic HCV in ...resource limited settings. Study results in HIV/HCV-coinfected patients are contradicting as to whether RBV concentration correlates with sustained virological response (SVR).
We included 262 HCV treatment naïve HIV/HCV-coinfected Swiss HIV Cohort Study (SHCS) participants treated with RBV and pegIFN between 01.01.2001-01.01.2010, 134 with HCV genotype (GT) 1/4, and 128 with GT 2/3 infections. RBV levels were measured retrospectively in stored plasma samples obtained between HCV treatment week 4 and end of therapy. Uni- and multivariable logistic regression analyses were used to evaluate the association between RBV concentration and SVR in GT 1/4 and GT 2/3 infections. The analyses were repeated stratified by treatment phase (week 4-12, 13-24, >24) and IL28B genotype (CC versus CT/TT).
SVR rates were 35.1% in GT 1/4 and 70.3% in GT 2/3 infections. Overall, median RBV concentration was 2.0 mg/L in GT 1/4, and 1.9 mg/L in GT 2/3, and did not change significantly across treatment phases. Patients with SVR had similar RBV concentrations compared to patients without SVR in both HCV genotype groups. SVR was not associated with RBV levels ≥2.0 mg/L (GT 1/4, OR 1.19 0.5-2.86; GT 2/3, 1.94 0.78-4.80) and ≥2.5 mg/L (GT 1/4, 1.56 0.64-3.84; GT 2/3 2.72 0.85-8.73), regardless of treatment phase, and IL28B genotype.
In HIV/HCV-coinfected patients treated with pegIFN/RBV, therapeutic drug monitoring of RBV concentrations does not enhance the chance of HCV cure, regardless of HCV genotype, treatment phase and IL28B genotype.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PURPOSE OF REVIEWLiver disease is a major cause of morbidity and mortality in HIV-infected persons. The long-term beneficial versus potentially harmful influence of antiretroviral therapy (ART) on ...the liver is debated. We review current data on factors contributing to liver disease in HIV-monoinfected as well as in HIV/viral hepatitis-coinfected patients, highlighting the role of ART, HIV itself, immunodeficiency, patient characteristics, and lifestyle risk factors.
RECENT FINDINGSNew ART-related clinical syndromes, including noncirrhotic portal hypertension and nonalcoholic fatty liver disease, have emerged, and observational data suggest long-term ART-associated liver injury. Recently, there is increasing evidence that HIV itself and immunosuppression are contributing to liver injury in both HIV-coinfected and HIV-monoinfected patients. In HIV-positive persons, ART attenuates progression of chronic viral hepatitis.
SUMMARYCurrent expert guidelines recommend earlier treatment of HIV infection in persons coinfected with hepatitis B virus and possibly hepatitis C virus. It is unknown whether an earlier start of ART is beneficial for the liver in HIV-monoinfected patients. Future research should focus on long-term ART-related hepatotoxicity.
PDF
