Whether human immunodeficiency virus (HIV) infection is a risk factor for heart failure (HF) is not clear. The presence of coronary heart disease and alcohol consumption in this population may confound this association.
To determine whether HIV infection is a risk factor for incident HF, we conducted a population-based, retrospective cohort study of HIV-infected and HIV-uninfected veterans enrolled in the Veterans Aging Cohort Study Virtual Cohort (VACS-VC) and the 1999 Large Health Study of Veteran Enrollees (LHS) from January 1, 2000, to July 31, 2007.
There were 8486 participants (28.2% HIV-infected) enrolled in the VACS-VC who also participated in the 1999 LHS. During the median 7.3 years of follow-up, 286 incident HF events occurred. Age- and race/ethnicity–adjusted HF rates among HIV-infected and HIV-uninfected veterans were 7.12 (95% confidence interval [CI],6.90-7.34) and 4.82 (95% CI, 4.72-4.91) per 1000 person-years, respectively. Compared with HIV-uninfected veterans, those who were HIV infected had an increased risk ofHF (adjusted hazard ratio [HR], 1.81; 95% CI, 1.39-2.36). This association persisted among veterans who did not have a coronary heart disease event or a diagnosis related to alcohol abuse or dependence before the incident HF event (adjusted HR, 1.96; 95% CI, 1.29-2.98). Compared with HIV-uninfected veterans, those who were HIV infected with a baseline Human immunodeficiency virus 1 (HIV-1) RNA level of 500 or more copies/mL had a higher risk of HF (adjusted HR, 2.28; 95% CI, 1.57-3.32), while those with baseline and a recent HIV-1 RNA level less than 500 copies/mL did not (adjusted HR, 1.10; 95% CI, 0.64-1.89; P< .001 for comparison between high and low HIV-1 RNA groups).
Our data suggest that HIV infection is a risk factor for HF. Ongoing viral replication is associated with a higher risk of developing HF.
Patients with human immunodeficiency virus (HIV) infection are at increased risk of developing coronary heart disease (CHD). Although factors potentially contributing to this elevated risk include traditional CHD risk factors and antiretroviral medications, more recent data support a role for inflammatory and immunologic factors as central to a complex mechanism. Decreasing CHD risk among HIV-infected patients is likely to involve modification of inflammatory and immunologic factors through antiretroviral therapy or other novel strategies as well as targeted treatment of traditional CHD risk factors. This review will highlight epidemiologic data investigating the association between HIV and CHD outcomes. An overview of potential mechanistic factors associated with CHD in HIV infection and of strategies for managing CHD risk in HIV-infected patients is also included. Specific cardiovascular and metabolic risk factors, CHD risk prediction, and the immunologic basis for CHD in HIV-infected patients will be discussed in separate reviews.
Rationale: In aging HIV-infected populations comorbid diseases are important determinants of morbidity and mortality. Pulmonary diseases have not been systematically assessed in the combination antiretroviral therapy (ART) era.
Objectives: To determine the incidence of pulmonary diseases in HIV-infected persons compared with HIV-uninfected persons.
Methods: We analyzed data from the Veterans Aging Cohort Study Virtual Cohort, consisting of 33,420 HIV-infected veterans and 66,840 age, sex, race and ethnicity, and site-matched HIV-uninfected veterans. Using Poisson regression, incidence rates and adjusted incidence rate ratios were calculated to determine the association of HIV with pulmonary disease. The Virtual Cohort was merged with the 1999 Veterans Large Health Survey to adjust for self-reported smoking in a nested sample (14%).
Measurements and Main Results: Incident chronic obstructive pulmonary disease, lung cancer, pulmonary hypertension, and pulmonary fibrosis, as well as pulmonary infections, were significantly more likely among HIV-infected patients compared with uninfected patients in adjusted analyses, although rates of asthma did not differ by HIV status. Bacterial pneumonia and chronic obstructive pulmonary disease were the two most common incident pulmonary diseases, whereas opportunistic pneumonias were less common. Absolute rates of most pulmonary diseases increased with age, although the relative differences between those with and without HIV infection were greatest in younger persons. Chronic obstructive pulmonary disease and asthma, as well as pulmonary infections, were less likely in those with lower HIV RNA levels and use of ART at baseline.
Conclusions: Pulmonary diseases among HIV-infected patients receiving care within the Veterans Affairs Healthcare System in the combination ART era reflect a substantial burden of non–AIDS-defining and chronic conditions, many of which are associated with aging.
HIV; respiratory tract diseases; lung diseases, obstructive; pneumonia; pneumonia, bacterial
The frequency of coronary heart disease (CHD) is increasing among HIV seropositive persons. This phenomenon may be related to HIV disease itself, the use of antiretroviral medications and increased length of survival, or the synergism of these factors. In this study we have calculated the 10-year CHD risk estimate and the prevalence of metabolic syndrome in a cohort of 118 HIV seropositive chronic drug users, including those who are on HAART with or without protease inhibitors (PI). The results showed that the 10-year coronary heart disease risk among the HIV seropositive drug users was 4.8 ± 5.7, which is within the range of results published for other HIV infected cohorts. The 10-year CHD risk was significantly higher in men (5.9±6.1, p<0.001) than in women (1.7±2.4), due to their gender and the pre-menopausal mean age of the women (39.4±7.3 years of age), despite a significantly higher rate of abdominal obesity (54.8% in women vs. 8.1% in men, p<0.001) and lower HDL (61.3% in women vs. 40% in men, p=0.042). The rate of metabolic syndrome among our female HIV seropositive drug users was significantly higher (29% vs 10.3%, p=0.013) compared to men (10.3%). Participants with metabolic syndrome had a significantly higher 10-year CHD risk (27.8% vs. 10.2%, p=0.041) and higher mean BMI (28.6 ± 4.1 vs. 24.2±4, p<0.001) than those without the syndrome. The predominant proportion of the cohort had a high viral load, suggesting that their use of illicit drugs has an influence on either adherence or effectiveness of antiretroviral medication. Increased viral load was significantly associated with metabolic syndrome (OR=2.23, 95% CI:1.12, 4.47; p=0.023), high fasting glucose (OR=1.61, 95% CI: 1.02, 2.55; p=0.042) and low HDL levels (OR=1.41, 95% CI: 1.01, 1.98; p=0.046), after controlling for age gender, smoking, PI exposure, BMI and CD4. HAART with or without PI did not significantly impact the 10-year CHD risk estimate or metabolic syndrome in this cohort. The estimated effect of PI, however, was positively and significantly related to triglyceride levels (effect estimate=95.81; 95% CI:39.40, 152.21; p<0.01) after controlling for age, gender, smoking, viral load, CD4 cell count and BMI. Heavy use of cigarettes and crack/cocaine was inversely associated with obesity (OR=0.84, 95% CI:0.67, 0.99; p=0.049; OR=0.43, 95% CI:0.19, 0.98; p=0.044, respectively), while use of marijuana tended to be associated with increased central obesity (p=0.08). Heavy cigarette smoking was significantly associated with low HDL (OR=3.06, 95% CI:1.18; 7.95, p=0.02). The significant association of higher viral load with CHD risk indicates that controlling viral load may be important in reducing CHD risk in HIV infected drug users.
Coronary heart disease risk; HIV; metabolic syndrome
Preventing coronary heart disease (CHD) is critical to further extending survival among human
immunodeficiency virus (HIV)-infected persons. Previously published findings of CHD risk factors in HIV-infected
persons have been derived from facility-based cohort studies, which have limited representativeness for the HIV-infected
population. State-specific, population-based surveillance data can assist health care providers and public health agencies
in planning and evaluating programs that reduce CHD among HIV-infected persons. We describe CHD risk factors from
the 2007-2008 Oregon Medical Monitoring Project, a population-based survey of HIV-infected persons receiving care that
included both patient interview and medical record review. Among the 539 HIV-infected patients interviewed, the mean
age was 45.5 years. Diagnoses from the medical record associated with CHD risk included preexisting CHD (5%),
diabetes (11%), and hypertension (28%). Current smoking was reported by 46%; college graduates were less likely to
smoke compared with those with lesser education (21% versus 53%, respectively; P <.0001). Obesity was present among
17%. Among the 65% of the survey group with lipid values available, 55% had high-density lipoprotein cholesterol
(HDL) <40 mg/dL and 42% had triglycerides ≥ 200 mg/dL. Among the 15% of the survey group with either preexisting
CHD or diabetes, 42% had a non-HDL <130 mg/dL (target goal) and 38% smoked. Risk factors for CHD among HIVinfected
persons, particularly smoking and dyslipidemia, should be managed aggressively. Ongoing surveillance is
warranted to monitor changes in CHD risk factors in the HIV-infected population.
Human immunodeficiency virus; coronary disease; risk factors; smoking; dyslipidemias.
The association between hepatitis C virus (HCV) infection and coronary artery disease (CAD) is controversial. We conducted this study to determine and quantify this association.
We used an established, national, observational cohort of all HCV-infected veterans receiving care at all Veterans Affairs facilities, the Electronically Retrieved Cohort of HCV Infected Veterans, to identify HCV-infected subjects and HCV-uninfected control subjects. We used the Cox proportional-hazards model to determine the risk of CAD among HCV-infected subjects and control subjects.
We identified 82,083 HCV-infected and 89,582 HCV-uninfected subjects. HCV-infected subjects were less likely to have hypertension, hyperlipidemia, and diabetes but were more likely to abuse alcohol and drugs and to have renal failure and anemia. HCV-infected subjects had lower mean (± standard deviation) total plasma cholesterol (175 ± 40.8 mg/dL vs. 198 ± 41.0 mg/dL), low-density lipoprotein cholesterol (102 ± 36.8 mg/dL vs. 119 ± 38.2 mg/dL), and triglyceride (144 ± 119 mg/dL vs. 179 ± 151 mg/dL) levels, compared with HCV-uninfected subjects. In multivariable analysis, HCV infection was associated with a higher risk of CAD (hazard ratio, 1.25; 95% confidence interval, 1.20–1.30; P < .001 for all comparisons). Traditional risk factors (age, hypertension, chronic obstructive pulmonary disease, diabetes, and hyperlipidemia) were associated with a higher risk of CAD in both groups, whereas minority race and female sex were associated with a lower risk of CAD.
HCV-infected persons are younger and have lower lipid levels and a lower prevalence of hypertension. Despite a favorable risk profile, HCV infection is associated with a higher risk of CAD after adjustment for traditional risk factors.
To examine the association between HIV infection status and the receipt of lipid lowering therapy based on National Cholesterol Education Program/Adult Treatment Panel (NCEP/ATP III) guidelines and to assess whether HIV viral load and hepatitis C (HCV) status alters that association.
PARTICIPANTS AND DESIGN
A cross-sectional analysis of survey, laboratory, and pharmacy data from 1,577 male participants (59% HIV infected) of the Veterans Aging Cohort Five-Site Study, a prospective observational cohort of U.S. veterans with and without HIV infection.
Receipt of lipid lowering therapy obtained from the VA pharmacy benefits management system was the main outcome.
The prevalence of lipid lowering therapy among HIV-infected and HIV-uninfected veterans was 15.4% vs. 37.9%, respectively, < 0.01. Among veterans who met NCEP/ATP III criteria for lipid lowering therapy, HIV-infected veterans had a significantly lower prevalence for the receipt of lipid lowering therapy (adjusted odds ratio (OR) = 0.43, 95% confidence interval (C.I.) 0.28–0.67) as compared with HIV-uninfected veterans. Among HIV-infected veterans, log HIV viral load (adjusted OR = 0.57, 95% CI, 0.41–0.81) and HIV-HCV co-infection (adjusted OR = 0.31, 95% CI = 0.13–0.75) were negatively associated with receipt of lipid lowering therapy. Exposure to HAART was not associated with receipt of lipid lowering therapy.
Among those who met NCEP/ATP III criteria for lipid lowering therapy, HIV-infected veterans, particularly those with high HIV viral loads and HCV co-infection, were significantly less likely to receive lipid lowering therapy. This may be a modifiable mediator of cardiovascular disease among HIV-infected individuals.
HIV; cholesterol; hepatitis C; men; veterans; cardiovascular diseases
Coronary heart disease (CHD) is an inflammatory process that takes decades to develop. In HIV-seronegative persons, high-sensitivity C-reactive protein is a biologic marker of CHD risk. HIV infection induces chronic inflammation, despite adequate suppression of HIV replication with antiretroviral therapy, resulting in elevations of several biologic markers associated with CHD risk in HIV-seronegative persons. Indeed, the SMART study demonstrated that interruption in antiretroviral therapy is associated with higher mortality and CHD events postulated to be related to inflammatory mediators such as interleukin-6 and D-dimer. Specific antiretroviral agents (eg, abacavir) have been associated with higher rates of myocardial infarctions and elevations in markers of inflammation such as interleukin-6 and D-dimer in persons with CHD events. This article reviews the current understanding of biomarkers of inflammation associated with the development of CHD in the setting of HIV infection and the use of antiretroviral therapy.
HIV; Inflammation; Coronary heart disease; Surrogate markers; High-sensitivity C-reactive protein; D-dimer; Interleukin-6; Atherosclerosis; Endothelial dysfunction
To examine the effect of hepatitis C virus (HCV) on the prevalence of chronic kidney disease (CKD) among veterans with HIV and to evaluate independent associations of HCV and CKD with mortality.
We studied a national cohort of HIV-infected patients receiving care through the Veterans Healthcare Administration from 1998 to 2004. CKD was defined as an estimated glomerular filtration rate [eGFR (mL/min/1.73 m2)] < 60. Poisson regression was used to assess relationships between CKD, HCV, and mortality.
Among 23,155 HIV-infected veterans, 12% had CKD. Forty percent of the cohort was coinfected with HCV, and a higher proportion of coinfected subjects had CKD compared with monoinfected subjects (14% vs 11%, P < 0.001). During the median follow-up of 7.6 years, 37% of subjects died and a graduated increase in adjusted mortality rates occurred with lower levels of eGFR (P < 0.001). Adjusted mortality rates were consistently higher in HCV-coinfected subjects across all levels of eGFR (P < 0.001). HCV was independently associated with increased mortality (incidence rate ratio 1.23, 95% confidence interval 1.17–1.29).
CKD is prevalent in HIV-infected veterans and associated with substantially higher mortality. Compared with their monoinfected counterparts, veterans coinfected with HCV have significantly higher rates of CKD and mortality.
death; HIV; hepatitis C; kidney failure; veterans
Although guidelines in individuals not infected with the human immunodeficiency virus (HIV) consider diabetes mellitus (DM) to be a coronary heart disease (CHD) equivalent, there is little information on its association with CHD in those infected with HIV. We investigated the impact of DM and preexisting CHD on the development of a new CHD episode among 33 347 HIV-infected individuals in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D Study).
Methods and Results
Over 159 971 person-years, 698 CHD events occurred. After adjustment for gender, age, cohort, HIV transmission, ethnicity, family history of CHD, smoking, and calendar year, the rate of a CHD episode was 7.52 times higher (Poisson regression, 95% CI 6.02 to 9.39, P=0.0001) in those with preexisting CHD than in those without preexisting CHD, but it was only 2.41 times higher (95% CI 1.91 to 3.05, P=0.0001) in those with preexisting DM compared with those without DM. No statistical interactions were apparent between either diagnosis and sex; although older people with DM had an increased CHD rate compared with younger people, older people with preexisting CHD had a lower event rate. A statistically significant interaction between preexisting DM and CHD (P=0.003) suggested that the CHD rate in those with preexisting CHD and DM is lower than expected on the basis of the main effects alone.
DM and preexisting CHD are both important risk factors for CHD events in HIV-infected individuals. There is a need for targeted interventions to reduce the risk of CHD in both high-risk groups of HIV-infected individuals.
coronary disease; diabetes mellitus; risk factors; human immunodeficiency virus; epidemiology
How hepatitis C virus (HCV) affects coronary heart disease (CHD) risk factors and outcomes is largely unknown.
Methods and Results
Among a cohort of patients with stable CHD, we examined the association between HCV seropositivity and levels of inflammatory markers (C-reactive protein [CRP], fibrinogen, interleukin-6, and tumor necrosis factor [TNF]-α) and risk for the following outcomes: death, cardiovascular (CV) events, and heart failure events. A total of 84 (8.6%) participants were found to be seropositive for HCV. HCV-seropositive patients were found to have significantly lower adjusted mean levels of CRP (2.6 vs. 4.4; P <.01) and fibrinogen (340 vs. 398; P <.01), but higher levels of TNF-α (7.1 vs. 4.8; P <.01). Age-adjusted rates for HCV seropositive vs. seronegative were as follows: death 93 vs. 42/1,000 p-y (P <.01), CV events 62 vs. 40 (P = .13), and heart failure 76 vs. 29 (P <.01). After adjustment for demographic and clinical factors, HCV remained significantly associated with an increased risk for heart failure events (HR =2.13; 95% CI: 1.19–3.80).
In this cohort with CHD, HCV seropositive participants had higher rates of death, CVevents, and heart failure hospitalizations during follow-up. After adjustment for CV risk factors, HCV seropositivity remained independently associated with risk for heart failure events.
Hepatitis C virus; inflammatory markers; heart failure
Persons with HIV infection have been reported to develop age-related diseases at younger ages than those without HIV. Whether this finding is related to HIV infection or failure to control for other risk factors is unknown.
To investigate whether persons with HIV infection develop hepatitis C virus (HCV)–related liver disease at younger ages than similar persons without HIV.
Comparison of the severity of liver fibrosis by age among persons who have HCV with and without HIV followed concurrently in the same protocol.
Observational cohort from Baltimore, Maryland, participating in the ALIVE (AIDS Linked to the IntraVenous Experience) study.
1176 current and former injection drug users with antibodies to HCV.
Liver fibrosis assessed semiannually from 2006 to 2011 by elastography (FibroScan, Echosens, Paris, France) and using previously validated thresholds for clinically significant fibrosis and cirrhosis; concurrent assessment of medical history, alcohol and illicit drug use, HCV RNA levels, hepatitis B virus surface antigen level, body mass index, and (for those with HIV) CD4+ lymphocyte count and HIV RNA levels.
Among 1176 participants with antibodies to HCV, the median age was 49 years and 34% were coinfected with HIV and HCV. Participants contributed 5634 valid liver fibrosis measurements. The prevalence of clinically significant fibrosis without cirrhosis (12.9% vs. 9.5%) and of cirrhosis (19.5% vs. 11.0%) was greater in persons coinfected with HIV and HCV than in those with only HCV (P < 0.001). Increasing age and HIV infection were independently associated with liver fibrosis, as were daily alcohol use, chronic hepatitis B virus infection, body mass index greater than 25 kg/m2, and greater plasma HCV RNA levels. When these factors were kept constant, persons with HIV had liver fibrosis measurements equal to those of persons without HIV, who were, on average, 9.2 years older.
The process of liver fibrosis began before the study in most persons.
In this cohort, persons who have HCV with HIV have liver fibrosis stages similar to those without HIV who are nearly a decade older.
Treatment rates for hepatitis C virus (HCV) are low in actual clinical settings. However, the proportion of patients eligible for treatment, especially among those coinfected with HIV, is not well known. Our aim was to determine and compare the rates for HCV treatment eligibility among HCV and HCV-HIV-coinfected persons. We assembled a national cohort of HCV-infected veterans in care from 1998–2003, using the VA National Patient Care Database for demographic/clinical information, the Pharmacy Benefits Management database for pharmacy records, and the Decision Support Systems database for laboratory data. We compared the HCV-monoinfected and HCV-HIV-coinfected subjects for treatment indications and eligibility using current treatment guidelines. Of the 27,452 subjects with HCV and 1225 with HCV-HIV coinfection, 74.0% and 84.6% had indications for therapy and among these, 43.9% of HCV-monoinfected and 28.4% of HCV-HIV-coinfected subjects were eligible for treatment. Anemia, decompensated liver disease (DLD), chronic obstructive pulmonary disease (COPD), recent alcohol abuse, and coronary artery disease were the most common contraindications in the HCV, and anemia, DLD, renal failure, recent drug abuse, and COPD in the HCV-HIV-coinfected group. Among those eligible for treatment, only 23% of the HCV-monoinfected and 15% of the HCV-HIV-coinfected subjects received any treatment for HCV. Most veterans with HCV are not eligible for treatment according to the current guidelines. Even for those who are eligible for treatment, only a minority is prescribed treatment. Several contraindications are modifiable and aggressive management of those may improve treatment prescription rates.
Perceived stress may increase risk for coronary heart disease (CHD) and death, but few studies have examined these relationships longitudinally. We sought to determine the association of perceived stress with incident CHD and all‐cause mortality.
Methods and Results
Data were from a prospective study of 24 443 participants without CHD at baseline from the national Reasons for Geographic And Racial Differences in Stroke (REGARDS) study cohort. Outcomes were expert‐adjudicated acute CHD and all‐cause mortality. Over a mean follow‐up of 4.2 (maximum 6.9) years, there were 659 incident CHD events and 1320 deaths. Analyses were stratified by income level because of significant interactions with stress. For individuals with low income, 3529 (35.4%) reported high stress, and for those with high income, 2524 (22.1%) did so. Compared with reporting no stress, those reporting the highest stress had higher risk for incident CHD if they reported low income (sociodemographic‐adjusted HR 1.36, 95% CI: 1.04, 1.78) but not high income (sociodemographic‐adjusted HR 0.82, 95% CI: 0.57, 1.16); the finding in low income individuals attenuated with adjustment for clinical and behavioral factors (HR 1.29, 95% CI: 0.99, 1.69, P=0.06). After full adjustment, the highest stress category was associated with higher risk for death among those with low income (HR 1.55, 95% CI: 1.31, 1.82) but not high income (HR 1.13, 95% CI: 0.88, 1.46).
High stress was associated with greater risks of CHD and death for individuals with low but not high income.
epidemiology; mortality; myocardial infarction; stress
Inflammation is a potential mechanism to explain the accelerated atherosclerosis observed in HIV- and hepatitis C virus (HCV)–infected persons. We evaluated C-reactive protein (CRP) in HIV-infected and HIV/HCV-coinfected individuals in the era of effective antiretroviral (ARV) therapy.
Cross-sectional study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM) cohort and controls from the Coronary Artery Risk Development in Young Adults (CARDIA) study.
CRP levels were measured in 1135 HIV-infected participants from the FRAM cohort and 281 controls from the CARDIA study. The associations of HIV and HIV/HCV infection with CRP levels were estimated by multivariable linear regression.
Compared with controls, HIV monoinfection was associated with an 88% higher CRP level in men (P < 0.0001) but with no difference in women (5%; P = 0.80) in multivariate analysis. CRP levels were not associated with ARV therapy, HIV RNA level, or CD4 cell count. Compared with controls, HIV/HCV coinfection was associated with a 41% lower CRP level in women (P = 0.012) but with no difference in men (+4%; P = 0.90). Among HIV-infected participants, HCV coinfection was associated with 50% lower CRP levels after multivariable analysis (P < 0.0001) in men and women. Greater visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were strongly associated with CRP levels. Among HIV- infected participants, CRP levels were 17% (P < 0.001) and 21% (P = 0.002) higher per doubling of VAT and SAT; among controls, CRP levels were 34% (P < 0.001) and 61% (P = 0.009) higher, respectively.
In the absence of HCV coinfection, HIV infection is associated with higher CRP levels in men. HCV coinfection is associated with lower CRP levels in men and women.
cardiovascular disease; C-reactive protein; hepatitis C virus; HIV; inflammation
There is emerging evidence that Hepatitis C virus (HCV) infection plays a role in the etiology of immune thrombocytopenia purpura (ITP) and autoimmune hemolytic anemia (AIHA) which both are severe autoimmune cytopenias.
In order to determine if HCV infection increases the risk for ITP and AIHA, we calculated the incidence rates of ITP and AIHA among 120,691 HCV-infected and 454,905 matched HCV-uninfected U.S. veterans diagnosed 1997–2004. After excluding individuals with a prior diagnosis of a lymphoproliferative disease, HIV, or cirrhosis, we fit Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) as measures of risks.
We found 296 ITP and 90 AIHA cases. Among HCV-infected versus HCV-uninfected persons, the overall incidence rates of ITP were 30.2 and 18.5 per 100,000 person-years, and for AIHA they were 11.4 and 5.0 per 100,000 person-years, respectively. HCV was associated with elevated risks for ITP (HR=1.8, 95% CI 1.4–2.3) and AIHA (HR=2.8, 95% CI 1.8–4.2). ITP incidence was increased among both untreated and treated HCV-infected persons (HR 1.7, 95% CI 1.3–2.2, and HR 2.4, 95% CI 1.5–3.7, respectively), whereas AIHA incidence was elevated only among treated HCV-infected persons (HR 11.6, 95% CI 7.0–19.3).
Individuals infected with HCV are at an increased risk for ITP, while the development of AIHA appears to be associated with HCV treatment. It may be beneficial to test individuals newly diagnosed with ITP for HCV infection.
As those with HIV infection live longer, ‘non-AIDS’ condition associated with immunodeficiency and chronic inflammation are more common. We ask whether ‘non-HIV’ biomarkers improve differentiation of mortality risk among individuals initiating combination antiretroviral therapy (cART).
Using Poisson models, we analysed data from the Veterans Aging Cohort Study (VACS) on HIV-infected veterans initiating cART between 1 January 1997 and 1 August 2002. Measurements included: HIV biomarkers (CD4 cell count, HIV RNA and AIDS-defining conditions); ‘non-HIV’ biomarkers (haemoglobin, transaminases, platelets, creatinine, and hepatitis B and C serology); substance abuse or dependence (alcohol or drug); and age. Outcome was all cause mortality. We tested the discrimination (C statistics) of each biomarker group alone and in combination in development and validation data sets, over a range of survival intervals, and adjusting for missing data.
Of veterans initiating cART, 9784 (72%) had complete data. Of these, 2566 died. Subjects were middle-aged (median age 45 years), mainly male (98%) and predominantly black (51%). HIV and ‘non-HIV’ markers were associated with each other (P<0.0001) and discriminated mortality (C statistics 0.68–0.73); when combined, discrimination improved (P<0.0001). Discrimination for the VACS Index was greater for shorter survival intervals [30-day C statistic 0.86, 95% confidence interval (CI) 0.80–0.91], but good for intervals of up to 8 years (C statistic 0.73, 95% CI 0.72–0.74). Results were robust to adjustment for missing data.
When added to HIV biomarkers, ‘non-HIV’ biomarkers improve differentiation of mortality. When evaluated over similar intervals, the VACS Index discriminates as well as other established indices. After further validation, the VACS Index may provide a useful, integrated risk assessment for management and research.
anaemia; CD4 cell count; hepatitis C coinfection; hepatology; injecting drug use; outcomes; renal/kidney; risk groups; viral load
Hepatitis C virus (HCV)/human immunodeficiency virus (HIV) co-infection has become a serious public health problem especially in high risk groups such as injection drug users in China. However, the impact of HIV infection and antiretroviral therapy (ART) on HCV viral load which is usually regarded as a predictor of liver disease progress had not been well studied in this country.
To explore correlations of HIV co-infection and ART with plasma HCV load among HCV-infected patients in an ethnic minority area in Yunnan Province, China.
Patients and Methods
HCV/HIV co-infected patients and HCV mono-infected controls were examined and compared for plasma HCV RNA and related risk factors.
A total of 145 HCV/HIV co-infected patients and 25 HCV mono-infected controls were studied. The majority of the participants were male, belonged to an ethnic minority and were younger than 45 years old. HCV viral suppression rate with undetectable plasma HCV viral load was 28.3% in the HCV/HIV co-infected patients, 36% among HCV mono-infected controls and 29.4% overall. ART-prescribed HCV/HIV co-infected patients had significantly higher HCV viral loads (IQR: (3.80-6.44)*log10 copies ml-1) than those naïve to ART (IQR: (undetectable-6.41)*log10 copies ml-1) and HCV mono-infected patients (IQR: (undetectable-5.44)*log10 copies ml-1). Men, from the Dai minority and those with more than six years education, were also shown to have a higher plasma HCV viral load,according to multiple logistic regression analysis.
ART potentially increases the plasma HCV viral load among HCV/HIV coinfected patients in an ethnic minority area in China. Future large scale prospective cohort studies are needed to address the controversy associated between HIV co-infection and the natural history of HCV.
HIV; Coinfection; Antiretroviral therapy, Highly Active; Viral load
Coinfection with hepatitis C (HCV) significantly increases the risk of acute and chronic renal disease in HIV-infected individuals. However, the burden of acute kidney injury (AKI) directly attributable to HIV among HCV-infected individuals and associated risk factors are not well understood. Within a prospective cohort, AKI episodes were identified by a rise in creatinine of 0.5 mg/dL. Incidence of first AKI events was calculated for HIV/HCV coinfected versus HCV monoinfected subjects, and multivariable analyses using Cox proportional hazards were performed to identify predictors of AKI. Throughout the study period, 35% HIV/HCV coinfected and 17% HCV monoinfected subjects developed AKI, with incidence of 8.74/100 person-years and 3.53/100 person-years, respectively (hazard ratio (HR) 2.48; [95% confidence interval (CI) 1.50, 3.74]). In multivariable analysis, HIV coinfection (HR 2.19 [1.33, 3.62]), decompensated cirrhosis (HR 6.64 [3.81, 11.6]), and cocaine use (HR 2.06 [1.15, 3.71]) were independently associated with AKI. HCV genotype, HCV viral load, hazardous drinking, and heroin use were not associated with AKI. Study limitations included potential misclassification bias of HCV-infected individuals as serial HIV antibody testing was not routinely performed after study entry, and inability to adjust for tenofovir use in multivariable analysis. In conclusion, among subjects with HCV infection, decompensated cirrhosis, HIV coinfection, and cocaine use are associated with increased risk of AKI. These findings highlight the importance of preventing and treating cirrhosis, controlling HIV coinfection, and reducing cocaine use in HIV/HCV coinfected persons.
To determine the associations of hepatitis C virus (HCV) infection with insulin resistance and abnormal glucose tolerance in a cohort of older adults with or at risk of HIV infection.
A cross-sectional study of 267 HIV-infected and 179 at-risk-uninfected adults without a history of diabetes mellitus.
HCV antibody assays and RNA levels were performed to assess HCV status. Antiretroviral use, family history of diabetes, sedentary behavior, and sociodemographic data were obtained using standardized interviews. Fasting insulin levels and oral glucose tolerance tests were performed to assess two outcomes, the homeostasis model assessment of insulin resistance and abnormal glucose tolerance [impaired glucose tolerance (IGT) or diabetes].
Of 446 participants, 265 (59%) were HCV seropositive; of these, 199 (75%) had detectable HCV-RNA levels. Insulin resistance was greater among HCV-seropositive compared with seronegative participants, adjusting for body mass index, Hispanic ethnicity, age greater than 55 years, sedentary behavior (watching television > 4 h/day), HIV status, HAART, and protease inhibitor (PI) use. Ninety-eight participants (22%) had abnormal glucose tolerance (69 with IGT and 29 with diabetes). Among HIV-infected participants, 25% were on non-PI HAART and 52% were on PI HAART, but HAART and PI use were not associated with insulin resistance or abnormal glucose tolerance. Among obese participants, abnormal glucose tolerance was more common in HCV-seropositive than seronegative individuals, whereas among non-obese participants there was no association.
The potential impact of HCV co-infection and obesity on glucose metabolism should be recognized in clinical care, and addressed in future research studies of HIV-infected individuals.
Hepatitis C virus; HIV; impaired glucose tolerance; insulin resistance; obesity; type 2 diabetes
The impact of highly active antiretroviral therapy (HAART) on progression to end-stage liver disease (ESLD) in human immunodeficiency virus (HIV)/ hepatitis C virus (HCV) co-infection remains controversial.
We studied 157 HCV+ hemophilic men (85 HIV+, 72 HIV−), on whom dates of HIV and HCV serovconversion and clinical outcomes were known. Time to ESLD was determined by Kaplan Meier product-limit methods, and risk factors for ESLD progression were analyzed by a Cox proportional hazards model.
Among HIV+ men, ESLD was more common, 17 of 85 (20.0%) than in HIV−, 8 of 72 (11.1%) and median ESLD-free survival significantly shorter, p = 0.009, hazard ratio 3.00 [95%CI: 1.27–7.08]. HAART treated HIV+ had longer ESLD-free survival than HIV+ untreated, 30.3 vs. 20.0 yr, p = 0.043, hazard ratio, 3.14 [95% CI: 1.27–7.08], comparable to survival in HIV-men, p = 0.13, hazard ratio 2.20 [95% CI: 0.76–2.35]. Progression was unrelated to HAART toxicity (n=0) or HCV antiviral therapy (n=7). HIV+ HAART Rx and HIV− did not differ in HCV duration, age at ESLD, age at death or present, overall or AIDS mortality, all p > 0.05.
These data suggest HAART improves ESLD-free survival, approaching that in HIV− men.
Highly active antiretroviral therapy; hepatitis C; endstage liver disease; HIV infection; survival; HIV-HCV co-infection
HCV incidence from 1996-2008 among HIV-infected men in U.S. HIV therapeutic trials was 0.51 per 100 person-years. Incident HCV occurred primarily through non-parenteral means; 75% of seroconverters reported no drug injection. At-risk HIV-infected persons should have access to HCV surveillance
Background. Outbreaks of sexually transmitted hepatitis C virus (HCV) infection have been reported among human immunodeficiency virus (HIV)–infected men who have sex with men in Europe, Australia, and New York. Whether this is occurring across the United States is unknown.
Methods. We determined incidence of HCV infection during 1996–2008 among male participants of the AIDS Clinical Trial Group Longitudinal Linked Randomized Trials cohort, a long-term study of HIV-infected persons randomized into selected US-based clinical trials. We evaluated associations with self-reported injection drug use (IDU), time-varying CD4+ cell count, and HIV RNA level with use of multivariate Poisson regression. No sexual or non-IDU risk factor data was available.
Results. A total of 1830 men had an initial negative HCV antibody test result and at least 1 subsequent HCV antibody test result, contributing >7000 person-years. At the time of the initial negative HCV antibody test result, 94% of men were receiving highly active antiretroviral therapy (HAART) and 6% reported current or prior IDU. Thirty-six seroconverted, with overall incidence of .51 cases per 100 person-years (95% confidence interval, .36–.70). Mean age at seroconversion was 46 years. Seroconversion was associated with IDU (25% of seroconverters reported IDU history vs 5% of nonseroconverters; P < .001), whereas 75% (n = 27) of seroconverters reported no IDU (incidence, 2.67 cases per 100 person-years among IDUs, .40 cases per 100 person-years among non-IDUs). Seroconversion was associated with HIV RNA level >400 copies/mL (44% at time of antibody positivity vs 21% at time of last negative antibody test result; P = .02) but not with CD4+ cell count.
Conclusions. Incident HCV infection occurs in HIV-infected men involved in US HIV therapeutic trials, primarily through nonparenteral means, despite engagement in care and HAART. HCV antibody development was not related to immune status but was associated with inadequate HIV suppression. At-risk HIV-infected persons should have access to HCV surveillance.
Data from prospective cohort studies regarding the association between subclinical hyperthyroidism and cardiovascular outcomes are conflicting. We aimed to assess the risks of total and coronary heart disease (CHD) mortality, CHD events, and atrial fibrillation (AF) associated with endogenous subclinical hyperthyroidism among all available large prospective cohorts.
Individual data on 52 674 participants were pooled from 10 cohorts. Coronary heart disease events were analyzed in 22 437 participants from 6 cohorts with available data, and incident AF was analyzed in 8711 participants from 5 cohorts. Euthyroidism was defined as thyrotropin level between 0.45 and 4.49 mIU/L and endogenous subclinical hyperthyroidism as thyrotropin level lower than 0.45 mIU/L with normal free thyroxine levels, after excluding those receiving thyroid-altering medications.
Of 52 674 participants, 2188 (4.2%) had subclinical hyperthyroidism. During follow-up, 8527 participants died (including 1896 from CHD), 3653 of 22 437 had CHD events, and 785 of 8711 developed AF. In age-and sex-adjusted analyses, subclinical hyperthyroidism was associated with increased total mortality (hazard ratio [HR], 1.24, 95% CI, 1.06–1.46), CHD mortality (HR, 1.29; 95% CI, 1.02–1.62), CHD events (HR, 1.21; 95% CI, 0.99–1.46), and AF (HR, 1.68; 95% CI, 1.16–2.43). Risks did not differ significantly by age, sex, or preexisting cardiovascular disease and were similar after further adjustment for cardiovascular risk factors, with attributable risk of 14.5% for total mortality to 41.5% for AF in those with subclinical hyperthyroidism. Risks for CHD mortality and AF (but not other outcomes) were higher for thyrotropin level lower than 0.10 mIU/L compared with thyrotropin level between 0.10 and 0.44 mIU/L (for both, P value for trend, ≤.03).
Endogenous subclinical hyperthyroidism is associated with increased risks of total, CHD mortality, and incident AF, with highest risks of CHD mortality and AF when thyrotropin level is lower than 0.10 mIU/L.
Because of major advances in the treatment of HIV /AIDS, HIV-positive persons now live longer, healthier lives; however, hepatitis C virus (HCV) is increasingly recognized as a major cause of morbidity and mortality in this population. Among HCV-infected persons, HIV co-infection is associated with increased HCV RNA levels, increased hepatic inflammation and fibrosis, and more rapid progression to cirrhosis and end-stage liver disease. Compounding this problem are reduced HCV treatment response rates among HCV /HIV co-infected persons. Moreover, antiretroviral therapy used to suppress HIV replication is often associated with a paradoxical increase in HCV RNA levels, as well as hepatotoxicity. Despite the adverse clinical consequences of HCV/ HIV co-infection, the mechanisms by which these two viruses interact at the cellular level remain largely unexplored. This review focuses on the evidence demonstrating direct infection of hepatocytes by HIV, as well as the indirect mechanisms by which HIV may regulate HCV replication at the cellular level. A comprehensive understanding of virus–virus and virus–cell interactions is critical to the development of novel treatment strategies to combat HCV/ HIV co-infection.
co-infection; hepatitis C virus; human immunodeficiency virus; liver
The role of serum uric acid as an independent risk factor for cardiovascular disease remains unclear although hyperuricemia is associated with cardiovascular disease such as coronary heart disease (CHD), stroke and hypertension.
A systematic review and meta-analysis using a random-effects model was conducted to determine the risk of CHD associated with hyperuricemia in adults. Studies of hyperuricemia and CHD were identified by searching major electronic databases using the Medical Subject Headings and keywords without language restriction (through February 2009). Only prospective cohort studies were included if they had data on CHD incidences or mortalities related to serum uric acid levels in adults.
26 eligible studies of 402,997 adults were identified. Hyperuricemia was associated with an increased risk of CHD incidence (unadjusted risk ratio (RR) 1.34; 95% confidence interval (CI) 1.19-1.49) and mortality (unadjusted RR 1.46; 95% CI 1.20-1.73). When adjusted for potential confounding, the pooled RR was 1.09 (95% CI: 1.03-1.16) for CHD incidence and 1.16 (95% CI: 1.01-1.30) for mortality. For each increase of 1 mg/dl in uric acid level, the pooled multivariate RR for CHD mortality was 1.12 (95% CI: 1.05-1.19). Subgroup analyses showed no significant association between hyperuricemia and CHD incidence/mortality in men, but an increased risk for CHD mortality in women (RR 1.67; 95% CI: 1.30-2.04).
Hyperuricemia may marginally increase the risk of CHD events, independently of traditional CHD risk factors. A more pronounced increased risk for CHD mortality in women should be investigated in future research.
hyperuricemia; coronary heart disease; meta-analysis