Browsing by Subject "human immunodeficiency virus"

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Open Access
Direct-Acting Antivirals Improve Access to Care and Cure for Patients With HIV and Chronic HCV Infection.
(Open Forum Infect Dis, 2018-01) Collins, Lauren F; Chan, Austin; Zheng, Jiayin; Chow, Shein-Chung; Wilder, Julius M; Muir, Andrew J; Naggie, Susanna
Background: Direct-acting antivirals (DAA) as curative therapy for hepatitis C virus (HCV) infection offer >95% sustained virologic response (SVR), including in patients with human immunodeficiency virus (HIV) infection. Despite improved safety and efficacy of HCV treatment, challenges remain, including drug-drug interactions between DAA and antiretroviral therapy (ART) and restrictions on access by payers. Methods: We performed a retrospective cohort study of all HIV/HCV co-infected and HCV mono-infected patients captured in care at our institution from 2011-2015, reflecting the DAA era, to determine treatment uptake and SVR, and to elucidate barriers to accessing DAA for co-infected patients. Results: We identified 9290 patients with HCV mono-infection and 507 with HIV/HCV co-infection. Compared to mono-infected patients, co-infected patients were younger and more likely to be male and African-American. For both groups, treatment uptake improved from the DAA/pegylated interferon (PEGIFN)-ribavirin to IFN-free DAA era. One-third of co-infected patients in the IFN-free DAA era required ART switch and nearly all remained virologically suppressed after 6 months. We observed SVR >95% for most patient subgroups including those with co-infection, prior treatment-experience, and cirrhosis. Predictors of access to DAA for co-infected patients included Caucasian race, CD4 count ≥200 cells/mm3, HIV virologic suppression and cirrhosis. Time to approval of DAA was longest for patients insured by Medicaid, followed by private insurance and Medicare. Conclusions: DAA therapy has significantly improved access to HCV treatment and high SVR is independent of HIV status. However, in order to realize cure for all, barriers and disparities in access need to be urgently addressed.
Open Access
Incidence, Long-Term Outcomes, and Healthcare Utilization of Patients With Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome and Disseminated Mycobacterium avium Complex From 1992-2015.
(Open Forum Infect Dis, 2017) Collins, Lauren F; Clement, Meredith E; Stout, Jason E
BACKGROUND: Despite the advent of combination antiretroviral therapy (cART), patients with human immunodeficiency virus (HIV) continue to develop late-stage complications including acquired immune deficiency syndrome (AIDS), disseminated Mycobacterium avium complex (DMAC), and death. METHODS: We performed an observational retrospective cohort study of HIV-infected adults who developed DMAC in the Duke University Health System from 1992 to 2015 to determine the incidence, long-term outcomes, and healthcare utilization of this population at high risk for poor outcomes. Findings were stratified by the "pre-cART" era (before January 1, 1996) and "post-cART" thereafter. RESULTS: We identified 330 adult HIV-infected patients newly diagnosed with DMAC, the majority (75.2%) of whom were male and non-Hispanic black (69.1%), with median age of 37 years. Incidence of DMAC declined significantly from 65.3/1000 in 1992 to 2.0/1000 in 2015, and the proportion of females and non-Hispanic blacks was significantly higher in the post-cART era. The standardized mortality ratios for DMAC patients who received cART were 69, 58, 27, 5.9, and 6.8 at years 1-5, respectively, after DMAC diagnosis. For patients diagnosed with DMAC in 2000 or later (n = 135), 20% were newly diagnosed with HIV in the 3 months preceding presentation with DMAC. Those with established HIV had a median time from HIV diagnosis to DMAC diagnosis of 7 years and were more likely to be black, rehospitalized in the 6 months after DMAC diagnosis, and die in the long term. CONCLUSIONS: Disseminated Mycobacterium avium complex continues to be a lethal diagnosis in the cART era, disproportionately afflicts minority populations, and reflects both delayed entry into care and failure to consistently engage care.
Open Access
Markers of Tissue Repair and Cellular Aging Are Increased in the Liver Tissue of Patients With HIV Infection Regardless of Presence of HCV Coinfection.
(Open forum infectious diseases, 2018-07) Naggie, Susanna; Swiderska-Syn, Marzena; Choi, Steve; Lusk, Sam; Lan, Audrey; Ferrari, Guido; Syn, Wing-Kin; Guy, Cynthia D; Diehl, Anna Mae
Liver disease is a leading cause of HIV-related mortality. Hepatitis C virus (HCV)-related fibrogenesis is accelerated in the setting of HIV coinfection, yet the mechanisms underlying this aggressive pathogenesis are unclear. We identified formalin-fixed paraffin-embedded liver tissue for HIV-infected patients, HCV-infected patients, HIV/HCV-coinfected patients, and controls at Duke University Medical Center. De-identified sections were stained for markers against the wound repair Hedgehog (Hh) pathway, resident T-lymphocytes, and immune activation and cellular aging. HIV infection was independently associated with Hh activation and markers of immune dysregulation in the liver tissue.
Open Access
Patterns of Healthcare Utilization Among Veterans Infected With Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV) and Coinfected With HIV/HCV: Unique Burdens of Disease.
(Open forum infectious diseases, 2016-09) Katrak, Shereen; Park, Lawrence P; Woods, Christopher; Muir, Andrew; Hicks, Charles; Naggie, Susanna
Background. Hepatitis C virus (HCV) infection is a leading cause of cirrhosis and the primary cause of liver transplantation in the United States, and coinfection with human immunodeficiency virus (HIV) increases the risk of comorbidities. However, healthcare utilization (HCU) patterns among HIV/HCV-coinfected patients are poorly understood. This study compared the rates of HCU and reasons for hospital admission among HCV-infected, HIV-infected, and HIV/HCV-coinfected veterans. Methods. Hepatitis C virus- and HIV-infected and HIV/HCV-coinfected veterans in care with the Department of Veterans Affairs (VA) from 1998 to 2009 (n = 335 371, n = 28 179, n = 13 471, respectively) were identified by HIV- and HCV-associated International Classification of Diseases, Ninth Revision codes from the clinical case registry. We assessed rates of HCU using emergency department (ED) visits, outpatient visits, and hospitalization and primary diagnoses associated with hospitalization. Independent risk factors associated with hospitalization were also examined. Results. Rates of outpatient and ED visits increased over the 11-year study period for all groups, with inpatient admission rates remaining stable. The HCU rates were consistently higher for the coinfected than other cohorts. The primary reason for hospital admission for all groups was psychiatric disease/substance use, accounting for 44% of all admissions. Nadir CD4 <350 cells/mm³ was associated with higher rates of hospitalization versus nadir CD4 >500 cells/mm³. Conclusions. As the current population of HCV-infected, HIV-infected, and HIV/HCV-coinfected veterans age, they will continue to place a substantial and increasing demand on the US healthcare system, particularly in their utilization of ED and outpatient services. These data suggest the need for an ongoing investment in mental health and primary care within the VA healthcare system.
Open Access
Prevalence of Early Cardiac Dysfunction in Children Living with Human Immunodeficiency Virus in Western Kenya
(2018) McCrary, Andrew
Background: HIV-associated cardiac dysfunction has severe consequences, and traditional measures of echocardiography underestimate disease. Novel echocardiographic measures may detect early disease in time for intervention. The aims of this study are to define the prevalence of early cardiac dysfunction in children living with HIV, and the relationships between cardiac function and same-day plasma HIV RNA levels.
Methods: Using a cross-sectional study design, we performed echocardiograms and obtained plasma HIV RNA levels on perinatally HIV-infected children engaged in care at Moi Teaching and Referral Hospital in Eldoret, Kenya. Early cardiac dysfunction was defined as normal ejection fraction but left ventricular global longitudinal strain (LV GLS) z-score < -2 or myocardial performance index (MPI) ≥ 0.5. The relationship between measures of cardiac function and HIV RNA levels and the assessment of other clinical covariates (age, sex, duration on antiretrovirals, and AZT exposure) with measures of cardiac function were modeled using multivariable regression.
Results: 302 perinatally HIV-infected children (mean age 9.8±3.2 years, range 2-16 years) were enrolled. The mean BMI-for-age z-s core was -1.0±1.1. The median duration on antiretrovirals was 5.4 years (IQR 3.2, 7.6). One hundred and sixteen children (38.4%) had been exposed to AZT (median duration of exposure 2.6 years, IQR 0.2, 5.4). One hundred and one of 298 (33.9%) had HIV RNA measurements ≥ 40 copies/ml. Only 1 of 302 children had LV GLS-for-BSA z-score ≤ -2 and normal ejection fraction meeting the criteria for early cardiac dysfunction, and 65 of 292 (22.3%) children had an MPI ≥ 0.5 and normal ejection fraction. In multivariate analysis, neither LVGLS z-score nor MPI were associated with HIV RNA levels ≥ 40 copies/ml or any clinical variables in the model [β -0.08 (95%CI -0.39, 0.23) and β 0.01 (95%CI -0.01, 0.03), respectively]. MPI was very weakly correlated with LVGLS z-score (r -0.15; 95%CI -0.26, -0.04).
Conclusions: Nearly one quarter of these perinatally HIV-infected children demonstrated echocardiographic evidence of early cardiac dysfunction, based primarily on abnormal MPI measurements. This finding was not correlated with same-day HIV RNA levels or other clinically relevant variables. Further investigation into the clinical significance of this finding is urgently needed as abnormal MPI measurements have been shown to be predictive of heart failure in at risk populations.