Events In HIV-infected Patients Research Articles

Development and Validation of the HIV-CARDIO-PREDICT Score to Estimate the Risk of Cardiovascular Events in HIV-Infected Patients.

Commonly used risk assessment tools for cardiovascular disease might not be accurate for HIV-infected patients. We aimed to develop a model to accurately predict the 10-year cardiovascular disease (CV) risk of HIV-infected patients. In this retrospective cohort study, adult HIV-infected patients seen at Boston Medical Center between March 2012 and January 2017 were divided into model development and validation cohorts. Boston Medical Center, a tertiary, academic medical center. Adult HIV-infected patients, seen in inpatient and outpatient setting. We used logistic regression to create a prediction risk model for cardiovascular events using data from the development cohort. Using a point-based risk-scoring system, we summarized the relationship between risk factors and cardiovascular disease (CVD) risk. We then used the area under the receiver operating characteristics curve (AUC) to evaluate model discrimination. Finally, we tested the model using a validation cohort. 1914 individuals met the inclusion criteria. The model had excellent discrimination for CVD risk [AUC 0.989; (95% CI: 0.986-0.993)] and included the following 11 variables: male sex (95% CI: 2.53-3.99), African American race/ethnicity (95% CI: 1.50-3.13), current age (95% CI: 0.07-0.13), age at HIV diagnosis (95% CI: -0.10-(-0.02)), peak HIV viral load (95% CI: 9.89 × 10-7-3.00 × 10-6), nadir CD4 lymphocyte count (95% CI: -0.03-(-0.02)), hypertension (95% CI: 0.20-1.54), hyperlipidemia (95% CI: 3.03-4.60), diabetes (95% CI: 0.61-1.89), chronic kidney disease (95% CI: 1.26-2.62), and smoking (95% CI: 0.12-2.39). The eleven-parameter multiple logistic regression model had excellent discrimination [AUC 0.957; (95% CI: 0.938-0.975)] when applied to the validation cohort. Our novel HIV-CARDIO-PREDICT Score may provide a rapid and accurate evaluation of CV disease risk among HIV-infected patients and inform prevention measures.

SMAD2/3 Phosphorylation Is Downregulated in T Cells in HIV-Infected Patients.

Persistent inflammation contributes to the exhaustion of immune system and non-AIDS-defining events in HIV-infected patients. Transforming growth factor β (TGF-β) is generally considered an anti-inflammatory cytokine. It is unclear that why high-level TGF-β coexists with chronic inflammation during HIV infection. In this study, it was found that HIV-infected patients had lower proportion of phosphorylated SMAD2/3-positive cells among total CD3+ T cells and subsets of CD3+CD8+ and CD3+CD8- T cells when compared with health subjects. The findings implied that phosphorylation of SMAD2/3 is inhibited in HIV-infected patients, and that disturbance of TGF-β/SMAD2/3 signaling pathway may be involved in HIV-related chronic inflammation.

Coronary Heart Disease in HIV-Infected Patients

Currently, there are methods of drug exposure to the infection caused by the human immunodeficiency viruses (HIV), that allow to suppress the active replication of the virus in the patient's body. The era of antiretroviral therapy, which has allowed HIV-infected people to live longer, has begun. This led to an increase in their cardiovascular diseases, which occur at an earlier age and are more severe than in people without HIV. Specific or “nontraditional” risk factors damaging vascular wall occur in HIV patients along with traditional risk factors. These factors include: the negative impact of HIV on endothelium, an imbalance of inflammatory mediators, pathological immune activation, a decrease in the level of CD4 cells, a change in the number and function of platelets. The question of the effect of antiretroviral therapy on the occurrence of atherosclerotic vascular lesions remains debatable. Acute coronary syndrome (ACS) is one of the most frequent and most severe cardiovascular events in HIV-infected patients. The risk of myocardial infarction is highest in patients with a viral load of HIV-1 ribonucleic acid (RNA)≥500 copies/ml and a CD4 cell count of <200/ml. The most common form of ACS in HIV patients is ACS with ST segment elevation. Treatment of ACS in HIV patients has some difficulties: a high frequency of stent thrombosis, the frequent occurrence of thrombocytopenia, drug interactions with antiretroviral therapy. The high risk of developing cardiovascular diseases in HIV patients necessitates the introduction of active measures of primary and secondary prevention, taking into account the specific interaction of all drugs taken by the patient.

976. Development and Validation of a Risk Score for Predicting Cardiovascular Events in HIV-Infected Patients

BackgroundHIV-infected individuals are at higher risk for developing cardiovascular disease (CVD). We aimed to develop a model to predict 10-year cardiovascular (CV) risk given that commonly used CVD risk assessment tools might not be accurate for HIV-infected patients.MethodsWe conducted a retrospective cohort study of HIV-infected patients seen at Boston Medical Center between March 2012 and January 2017. Exclusion criteria are shown in Figure 1. Patients were divided into model development and validation cohorts. Logistic regression was used to create a risk model for CV events using data from the development cohort. The relationship between risk factors and CVD risk was summarized using a point-based risk-scoring system. Areas under the receiver-operating-characteristics curve (AUC) were used to evaluate model discrimination. The model was subsequently tested using the validation cohort.ResultsOf 3,867 eligible HIV-infected patients, 1,914 individuals met inclusion criteria (Figure 1). There were 256 CV events in the development cohort. Ten independent prognostic factors were incorporated into the prediction function (Pmodel < 0.001). The model had excellent discrimination for CVD risk [AUC 0.94; (95% CI:0.93–0.96)] (Figure 2) and included the following variables: male sex (P < 0.001), African-American ethnicity (P = 0.023), current age (P = 0.020), age at HIV diagnosis (P = 0.006), peak HIV viral load (P = 0.012), nadir CD4 lymphocyte count (P < 0.001), hypertension (P < 0.001), hyperlipidemia (P = 0.001), diabetes (P < 0.001), and chronic kidney disease (P < 0.001). Scoring system and score sheets of risk estimates were developed to predict CV events in a 10-year follow-up period (Figures 3 and 4). The 10-parameter multiple logistic regression model also had excellent discrimination [AUC 0.96; (95% CI: 0.89–0.99)] when applied to the validation cohort.ConclusionWe developed and validated a risk-scoring system based on 10 clinical factors that accurately predict the 10-year risk for CV events in an HIV-infected population. This assessment tool may provide clinicians with a rapid assessment of cardiovascular disease risk among HIV-infected patients and inform prevention measures during the era of effective antiretroviral therapy. Disclosures All Authors: No reported Disclosures.

Hepatitis C virus and cumulative infections are associated with atherogenic cardiovascular events in HIV-infected subjects

Objectivesto analyze the association between HCV coinfection and cumulative infections with the development of a cardiovascular disease in HIV-infected subjects. MethodsHIV-infected subjects attended at Virgen del Rocio University Hospital, between January 1982 and March 2018, were considered if fulfilled the following criteria: at least two visits to the HIV clinic, clinical records with data about VZV reactivation and bacterial infections, available data on HCV coinfection status. Atherogenic cardiovascular events were registered. To analyze factors associated with the development of cardiovascular event, a logistic regression analysis was performed. Results823 subjects were included in the study. During the observational period, 58/823 (7.05%) developed a cardiovascular event. Advanced age at HIV-1 diagnosis, a low T-CD4 nadir, HCV coinfection and the burden of infections were independently associated with the risk of developing a cardiovascular event, apart from lipid levels and diabetes. Conclusionsboth HCV and the burden of infections are associated with an increased risk of cardivascular event in HIV-infected patients, together with other cardiovascular risk factors. Therapeutic strategies such as HCV erradication or VZV immunization could ameliorate cardiovascular risk in these subjects.

Metabolic events in HIV-infected patients using abacavir are associated with erythrocyte inosine triphosphatase activity.

Abacavir use has been associated with an increased risk of cardiovascular disease (CVD) and metabolic events in HIV-infected patients, although this finding was not consistently found. It is unclear whether abacavir only increases this risk in subpopulations of HIV-infected patients. It may be hypothesized that inosine 5'-triphosphate pyrophosphohydrolase (ITPase), an enzyme involved in the metabolism of purine analogues used in HIV treatment, plays a role in the risk of CVD and metabolic events in HIV-infected patients. ITPase activity and ITPA genotype were determined in 393 HIV-infected patients. ITPase activity <4 mmol IMP/mmol Hb/h was considered decreased. ITPA polymorphisms tested were: c.94C>A (rs1127354) and c.124 + 21A>C (rs7270101). ORs were determined using generalized estimating equation models for developing CVD in patients who had ever been exposed to abacavir, tenofovir or didanosine and for developing metabolic events in patients currently using these drugs. In patients using abacavir, metabolic events were associated with ITPase activity. No association was demonstrated for tenofovir or didanosine. The OR for metabolic events was 3.11 in patients using abacavir with normal ITPase activity (95% CI 1.34-7.21; P = 0.008) compared with patients with decreased ITPase activity [adjusted for age, BMI, cumulative duration of combination ART (cART) use and the use of PI and NNRTI]. CVD was not associated with ITPase activity or ITPA genotype. This study shows, for the first time, that ITPase activity is associated with the occurrence of metabolic events in patients using abacavir. Further studies are needed to confirm this association and to elucidate the possible mechanism.

Observed versus predicted cardiovascular events and all-cause death in HIV infection: a longitudinal cohort study

BackgroundThe aim of the study was to assess the applicability of an algorithm predicting 10-year cardiovascular disease (CVD) generated in the setting of the Framingham Heart Study to a real-life, contemporary Italian cohort of HIV-positive subjects.MethodsThe study was an observational longitudinal cohort study. The probability for 10-year CVD events according to the Framingham algorithm was assessed in 369 consecutive HIV-positive participants free from overt CVD enrolled in 2004, who were followed for a median of 10.0 years (interquartile range, 9.1-10.1). Cardiovascular events included myocardial infarction, hospitalized heart failure, revascularized angina, sudden cardiac death, stroke, peripheral arterial disease.ResultsOver 3097 person-years of observation, we observed a total of 34 CVD events, whereas Framingham algorithm predicted the occurrence of 34.3 CVD events. CVD event rate was 11.0/1000 person-years of follow-up. In a receiver operating characteristics curve analysis, Framingham risk equation showed an excellent predictive value for incident CVD events (c-statistics, 0.83; 95% confidence interval, 0.76-0.90). In a multivariable Cox analysis, age, smoking and diabetes were independent predictors of CVD events. All-cause death rate was 20.0/1000 person-years of follow-up (n = 62 deaths). Causes of death included liver diseases (18), malignancies (14), AIDS-related (11); cardiovascular (9) and others (10). In a Cox analysis, age, AIDS diagnosis and chronic hepatitis were independent predictors of death.ConclusionsObserved CVD events in HIV-infected patients were well predicted by Framingham algorithm. Established major CVD risk factors are the strongest determinants of CVD morbidity in an Italian contemporary cohort of HIV-positive subjects. Interventions to modify traditional risk factors are urgently needed in HIV people.

Contribution of Oxidative Stress to Non-AIDS Events in HIV-Infected Patients.

Recognition of potentially modifiable mechanisms implicated in the pathogenesis of non-AIDS events (NAEs) might help improve outcomes of HIV-infected individuals. HIV infection has been associated with increased oxidative stress. We assessed the association between F2-isoprostanes and serious NAEs, and whether they improve the predictive performance of inflammation and coagulation biomarkers. Prospective multicenter cohort. Individuals who had an incident serious NAE and 2 sex- and age-matched participants with no events were selected. Measurement of F2-isoprostanes, highly sensitive C-reactive protein, interleukin-6, D-dimer, sCD14, sCD40, sCD163, and neopterin levels was performed in successive plasma samples collected from cohort inclusion. Biomarkers were measured in 78 participants developing serious NAEs or death, and 151 subjects with no events. Adjusted levels of F2-isoprostanes, and also of highly sensitive C-reactive protein, sCD14, and D-dimer were higher in individuals who developed serious NAEs, including or not non-AIDS deaths. The same results were observed when only samples collected since the time of achieving virological suppression were analyzed. The additive incorporation of each biomarker, ending with F2-isoprostanes, in an adjusted model was associated with a graded and significant increase in the quality of model fitting, and 94% sensitivity, 33% specificity, and 0.77 accuracy to predict serious NAEs including non-AIDS-related death. Oxidative stress is associated with a higher risk of serious NAEs, including non-AIDS deaths. This effect is independent and additive to biomarkers of inflammation, monocyte activation, and coagulation. Our results suggest that oxidative stress should be included among mechanisms to deal with to improve prognosis of HIV-infected individuals.

The Prevalence of Cerebral Microbleeds in HIV-Infected Hemophilia Patients

Objective: Several studies have shown that rates of cerebrovascular events in HIV-infected patients are increased in comparison to uninfected individuals. In addition, cerebral bleeding represents a serious complication in hemophilia patients. Recently, asymptomatic cerebral microbleeds (CMBs), which can be detected by highly sensitive techniques such as T2*-weighted magnetic resonance imaging (MRI), have emerged as an important marker for predicting symptomatic cerebral bleeding. The aim of the present study was to investigate the prevalence of CMBs in HIVinfected hemophilia patients and to evaluate the association between HIV infection and cerebral bleeding. Methods: All HIV-infected hemophilia patients (HIV+ HemPts) who visited our hospital from January 2015 to December 2016 were enrolled in this study. In addition, all HIV-uninfected hemophilia patients (HIV- HemPts) who visited our hospital in the same period were enrolled as controls. CMBs were assessed using T2*-weighted MRI. The relationship between cerebral bleeding and the patients’ clinical factors was examined. Results: Two HIV+ HemPts had symptomatic cerebral bleedings during the study period. Twenty-one asymptomatic HIV+ HemPts and 13 HIV- HemPts underwent T2*-weighted MRI. CMBs were observed in 7 HIV+ HemPts (30.4%) and 1 HIV- HemPts (7.7%). In the multivariate logistic regression analysis, HIV infection was the factor most closely related to cerebral bleeding (odds ratio: 9.78, p-value: 0.08). Conclusion: This is the first report to investigate the prevalence of CMBs in HIV-infected patients. The prevalence of CMBs or symptomatic cerebral bleeding in HIV+ HemPts was high in comparison to that in HIV- HemPts. The brain screening test by T2*-weighted MRI seems to be meaningful for HIV+ HemPts.

The CD4/CD8 Ratio is Inversely Associated with Carotid Intima-Media Thickness Progression in Human Immunodeficiency Virus-Infected Patients on Antiretroviral Treatment.

Inversion of the CD4/CD8 ratio (<1) has been identified as a surrogate marker of immunosenescence and an independent predictor of AIDS events in HIV-infected patients and mortality in the general population. We aimed to assess the association between the CD4/CD8 ratio and carotid intima-media thickness (cIMT) progression in treated HIV-infected patients as a marker of coronary heart disease. A longitudinal study was conducted during 3 years in 96 virally suppressed HIV-infected patients receiving antiretroviral treatment (ART). We analyzed the associations between the CD4/CD8 ratio, cardiovascular risk factors, and antiretroviral treatment (ART) and progression of subclinical atherosclerosis assessed using cIMT at baseline and after 3 years. Finally, 96 patients completed the study. Seventy six (79.1%) patients were male, aged 44 ± 10 years; 39 (40.6%) were on treatment with protease inhibitors; 49 (51.04%) with nonnucleoside reverse transcriptase inhibitors, 6 (6.25%) with integrase inhibitors, 3 (3.12%) with maraviroc, and 2 (2.08%) just with nucleoside reverse transcriptase inhibitors. The mean of ART exposition was 6.9 ± 5.9 years. Twenty six (27%) patients had family history of ischemic heart disease, 51 (53.12%) were smokers, 12 (12.5%) were hypertensive, 4 (4.16%) had type 2 diabetes, 23 (23.9%) had dyslipidemia, and 31 (32.3%) were infected with hepatitis C virus. Baseline cIMT was significantly associated with age (rho = 0.497; p < .001), basal glucemia (rho = 0.323; p = .001), triglycerides (rho = 0.232; p = .023), Framingham risk score (rho = 0.324; p = .001), CD4/CD8 ratio (rho = -0.176; p = .05), and dyslipidemia (0.72 ± 0.16 mm vs. 0.63 ± 0.11 mm; p = .029). In multivariable analysis where cardiovascular risk factor and ART were included, cIMT progression was inversely associated with CD4/CD8 ratio [odds ratio (OR) = 0.283; confidence interval (95% CI) 0.099-0.809; p = .019]. In conclusion, the inversion of CD4/CD8 ratio in treated HIV-infected patients is independently associated with cIMT progression, a marker of coronary heart disease. Therefore, it might be clinically useful as predictor of cardiovascular events.

Impact of HIV-1 tropism on the emergence of non-AIDS events in HIV-infected patients receiving fully suppressive antiretroviral therapy.

Objective:The impact of HIV-1 tropism on the emergence of non-AIDS events was evaluated in a cohort of 116 antiretroviral therapy (ART) responder patients.Methods:The patients were followed for the emergence of hypertension, renal impairment, metabolic and bone disorders (defined as non-AIDS events) each 8 weeks at standard visits. A V3 plasma sequence genotype analysis was performed at the time of ART initiation and the geno2pheno algorithm with the results that defines the false-positive rate (FPR) was used to infer HIV tropism. The associations between the non-AIDS events and the FPR at baseline were evaluated using the χ2 test for trend. A Cox-regression analysis using the counting process formulation of Andersen and Gill was performed to define whether the emergence of non-AIDS events was correlated to FPR.Results:The prevalence of at least one non-AIDS event resulted higher in patients with a FPR below 10% than in patients with a R5 virus (P = 0.033). Patients with a FPR below 5.0% most frequently developed non-AIDS events during ART (P = 0.01). A higher prevalence of patients with at least two AIDS events was found in the group of patients with a FPR below 5.0% with respect to the others (P < 0.001). At multivariate Cox-regression analysis, having an X4 virus and age were independently associated with a higher probability of non-AIDS event development.Conclusion:This study shows that an X4 virus, particularly a FPR less than 5%, is related to non-AIDS events development. Further studies are warranted to understand the mechanisms underlying this phenomenon.

Abstract 11790: New and Old Cardiovascular Disease Risk Models to Predict Events in HIV Infected Patients

Background: The high incidence of cardiovascular events in HIV infected patients creates the important challenge of performing an accurate risk assessment and initiating treatment in the most appropriate patients. The new Pooled Equations (PE) recommended by the recent ACC/AHA guidelines have not been tested in HIV infected patients and compared with the older Framingham Risk Score (FRS). Method: Cohort of 2,550 HIV infected patients (34% women) followed prospectively for a total of 10,695 patient-years. We compared the 10-year risk of events of 7.5% with PE versus a FRS level of 6%, for the dual purpose of assessing the validity of the new algorithm in HIV and verify whether lowering the threshold of the older algorithm may be equivalent to the new method. Results: Mean age was 49.7+/-7 years, and mean HIV exposure was 16.6+/-6 years. Total follow-up was 10,695 patient-years and 67 non-fatal myocardial infarctions and 2 CV deaths were recorded. PE&gt;7.5% and FRS&gt;6% predicted (44/69 and 49/69) and missed (25/69 and 20/69) the same number of true events. The Net Reclassification Index showed that PE&gt;7.5% is weaker than FRS&gt;6% to predict events (7% fewer events predicted) but better to predict non-events (14% more cases predicted to not occur). Table 1 shows the recommendation for statin therapy according to PE and FRS compared to current clinical practice within our institution: the 2 algorithms were not superior to what is currently implemented at our institution. Conclusions: In HIV infected patients the new PE&gt;7.5% algorithm performs similarly to a FRS&gt;6% to predict events but is better than the older algorithm to predict non-events. Neither model is superior to clinical practice as a method to select patients who should receive risk reduction therapies. (p-value for comparison of recommended vs actual statin prescription)

Cerebrovascular events in HIV-infected patients: an analysis of a cohort of 3203 HIV+ patients during the times of cART

Purpose/Aim: Cerebrovascular events (CVE) in HIV infected patients have become an increasingly relevant neurological complication. Data about the prevalence and clinical features of CVE in HIV infected patients since the introduction of combined Anti-Retroviral Therapy (cART) are rare. Methods: A retrospective study of HIV-infected patients with a CVE was performed from 2002 to 2011. During this time period 3203 HIV-infected patients were admitted to the University hospital of Münster, Germany. All patients had access to regular and long term treatment with cART. The clinical features were analyzed and the prevalence of ischemic stroke (IS), transient ischemic attack (TIA) and intracerebral bleeding (ICB) was calculated. Results: The total prevalence of all CVE was at 0.6% (95% CI: 0.3, 0.8) (0.4% for IS (95% CI: 0.2, 0.6), 0.2% for TIA (95% CI: 0.0, 0.3) and 0.1% for ICB (95% CI: 0.0, 0.2)) and the crude annual incidence rate at 59 per 100.000 for all events. The median CD4 cell count was 405/μl (25th to 75th percentile: 251–568). The majority of patients had AIDS. The median age was at 49 years (25th to 75th percentile: 40–69). Some events were associated with HIV-associated vasculopathy or viral co-infections. Most patients presented with multiple vascular risk factors. Conclusion: The study confirms that CVE occur in HIV-infected patients with a good immune status and at a young age. HIV infection has to be considered in young stroke patients. The rate of CVE in this study was constant when comparing to the pre-cART era. HIV associated vasculopathy and viral co-infections need to be considered in the diagnostics of stroke.

Prognostic Indicators for Recurrent Thrombotic Events in HIV-infected Patients with Acute Coronary Syndromes: Use of Registry Data From 12 sites in Europe, South Africa and the United States

AimsLimited data are available on prognostic indicators for HIV patients presenting with ACS. Methods and resultsData on consecutive patients with HIV infection receiving standard highly active antiretroviral therapy (HAART) presenting with ACS between January 2001 and September 2012 were collected. Cardiac death and myocardial infarction (MI) were the primary end-points. 10,050 patients with ACS were screened, and among them a total of 201 patients (179 [89%] males and a median age of 53 [47-62] years) were included, 48% of them admitted for ST-elevation myocardial infarction and 14% having left ventricular systolic dysfunction (LVSD) at discharge. CD4+ counts less than 200 cells/mm3 were reported in 18 patients (9%), and 136 patients (67%) were treated with nucleoside-reverse transcriptase inhibitors (NRTI). After a median of 24months (10–41), 30 patients (15%) died, 12 (6%) for cardiac reasons, 20 (10%) suffered a MI, 29 (15%) a subsequent revascularization, and 7 (3%) a stent thrombosis. Other than LVSD (hazard ratio=6.4 [95% confidence interval [CI]: 1.6-26: p=0.009]), the only other independent predictor of cardiac death was not being treated with NRTI (hazard ratio=9.9 [95% CI: 2.1-46: p=0.03); a CD4 cell count <200 cells/mm3 was the only predictor of MI (hazard ratio=5.9 [95% CI: 1.4-25: p=0.016]). ConclusionsHIV patients presenting with ACS are at significantly increased risk for cardiac death if not treated with NRTI, and at significantly increased risk of MI if their CD4 cell count is <200 cells/mm3, suggesting that the stage of HIV disease (and lack of NRTI treatment) may contribute to cardiovascular instability.

Coagulation and morbidity in treated HIV infection

HIV infected patients are at increased risk for venous and arterial thromboembolic events. Multiple markers related to inflammation (IL-6, TNFrI, C-reative protein) and coagulation (tissue factor expression, FVIII, thrombin, fibrinogen and D-dimer levels) are increased in HIV infection, and several are predictive of thrombotic risk and mortality in HIV disease. The mechanisms behind the risk for abnormal coagulation in HIV infection have not been fully elucidated, but may be related to a chronic immune activation and inflammatory state in both untreated and treated HIV infection. The contribution of traditional risk factors, including smoking and dyslipidemia, overly represented in HIV infected patients, must also be considered when assessing thrombotic risk in this setting. Currently, several interventional studies are aimed at reducing inflammation and cardiovascular risk in HIV disease and may provide insights into the determinants of clotting events in HIV infected patients.

Hepatitis Delta Is a Major Determinant of Liver Decompensation Events and Death in HIV-Infected Patients

Coinfection with hepatitis viruses is common in individuals infected with human immunodeficiency virus (HIV) and has become a leading cause of complications and death in those receiving antiretroviral therapy (ART). We retrospectively examined the effect of coinfection with hepatitis B, C, and/or D viruses (HBV, HCV, HDV, respectively) on liver decompensation events (ascites, variceal bleeding, encephalopathy, and/or hepatocellular carcinoma) and liver-related mortality in HIV-positive patients on regular follow-up since the year 2004 at a reference HIV clinic in Madrid, Spain. A total of 1147 HIV-infected patients (mean age, 42 years; 81% males; 46% intravenous drug users, 85.4% on ART) were analyzed. Mean follow-up was 81.2 ± 17.8 months. At baseline, 521 patients (45.4%) were HCV-antibody positive, 85 (7.4%) were hepatitis B surface antigen positive, and 17 (1.5%) were anti-HDV positive. A total of 233 HIV/HCV-coinfected patients received antiviral therapy for HCV, of whom 106 (45%) achieved sustained virologic response (SVR). Overall, 15 patients died of liver-related complications and 26 developed hepatic decompensation events. Taking as controls the 524 HIV-monoinfected patients, HDV coinfection (adjusted hazard ratio [AHR], 7.5; 95% confidence interval [CI], 1.84-30.8; P = .005) and baseline liver stiffness (AHR, 1.1; 95% CI, 1.07-1.13; P < .0001) were associated with a higher rate of liver-related morbidity and mortality. In contrast, SVR following hepatitis C therapy in HIV/HCV-coinfected patients was protective (AHR, 0.11; 95% CI, .01-.86; P = .03). Hepatitis delta is associated with a high rate of death and liver decompensation events in HIV-infected patients on ART.

Role of IL-6 in Mycobacterium avium–Associated Immune Reconstitution Inflammatory Syndrome

Immune reconstitution inflammatory syndrome (IRIS) is a major adverse event of antiretroviral therapy in HIV infection, and paradoxically occurs as HIV viremia is suppressed and CD4 T cell numbers recover. IRIS reflects pathogenic immune responses against opportunistic infections acquired during the period of immunodeficiency, but little is understood about the mechanisms of inflammatory pathology. In this study, we show that IL-6 and C-reactive protein levels transiently rise at the time of the IRIS event in HIV-infected patients, unmasking Mycobacterium avium complex infection after starting antiretroviral therapy. To directly test the role of IL-6 in IRIS pathology, we used a model of experimentally inducible IRIS in which M. avium-infected T cell-deficient mice undergo a fatal inflammatory disease after reconstitution with CD4 T cells. We find that IL-6 neutralization reduces C-reactive protein levels, alleviates wasting disease, and extends host survival during experimental IRIS. Moreover, we show that combined blockade of IL-6 and IFN-γ further reduces IRIS pathology, even after the onset of wasting disease. The combination of these clinical and experimental-model data show that the IL-6 pathway is not only a biomarker of mycobacterial IRIS but also a major mediator of pathology distinct from IFN-γ and may be a useful target for therapeutic intervention.

IFNL4 ss469415590 variant is a better predictor than rs12979860 of pegylated interferon-alpha/ribavirin therapy failure in hepatitis C virus/HIV-1 coinfected patients

A new transiently induced region (interferon-λ 4 protein; IFNL4) harbouring a dinucleotide variant ss469415590 (TT or ΔG), upstream of IFNL3 (IL28B), was recently found to be associated with hepatitis C virus (HCV) clearance. To determine the effect of IFLN4 ss469415590 variation on the HCV response to IFN-based therapy in HCV/HIV-1 coinfected patients, ss469415590 was genotyped in a cohort of 207 patients from our clinic. Treatment failure occurred in 77% of minor ΔG-allele carriers versus 48% of noncarriers, indicating that the ΔG allele was strongly associated with treatment failure. Importantly, multivariate logistic analysis revealed that ss469415590 genotype was a better predictor of treatment failure than rs12979860.

High incidence of serious adverse events in HIV-infected patients treated with a telaprevir-based hepatitis C virus treatment regimen

To report the rates of grade IV adverse events and hepatitis C virus (HCV) treatment discontinuation associated with the use of telaprevir, pegylated interferon, and ribavirin. Retrospective cohort analysis. The study included patients coinfected with HIV and HCV who underwent HCV treatment in a clinic-based setting with telaprevir, pegylated interferon, and ribavirin. The United States of America National Institutes of Health Division of AIDS grading system was used to rate severity of adverse events. Of the 24 consecutive patients treated for HCV using telaprevir/pegylated interferon/ribavirin, 50% (12/24) developed serious adverse events and 29% (7/24) discontinued HCV treatment due to adverse events, despite an intensive multidisciplinary monitoring approach. In this HIV clinic-based experience, a high rate of grade IV adverse events and treatment discontinuations were observed associated with HCV telaprevir-based treatment. Careful consideration of the risks and benefits of telaprevir-based therapy should be undertaken, given prospects for interferon-sparing therapy in the near future.

CD4+ lymphocyte count predicts recurrent thrombotic events in HIV-infected patients with acute coronary syndromes

CD4+ lymphocyte count predicts recurrent thrombotic events in HIV-infected patients with acute coronary syndromes