Dataset Information

Clinical Liver Disease Progression Among Hepatitis C-Infected Drug Users With CD4 Cell Count Less Than 200 Cells/mm(3) Is More Pronounced Among Women Than Men.

ABSTRACT: Background. ?Hepatitis C virus (HCV) infection is a leading cause of liver-related morbidity and mortality in the United States, and injection drug users are at particularly high risk. Methods. ?This prospective observational cohort study assessed the rate of, and risk factors for, clinical liver disease progression in a cohort of HCV monoinfected and human immunodeficiency virus (HIV)/HCV coinfected drug users using unadjusted and multivariate Cox proportional hazards regression analyses. Results. ?Of 564 subjects including 421 (75%) with HIV/HCV coinfection and 143 with HCV monoinfection, 55 (10%) had clinical liver disease progression during follow-up with a rate of 25.3 events per 1000 person-years. In unadjusted analysis, there was an interaction between sex and HIV status. In sex-stratified multivariate analysis, HIV/HCV-coinfected women with CD4 <200 cells/mm(3) had 9.99 times the risk of liver disease progression as HCV-monoinfected women (confidence interval [CI], 1.84-54.31; P = .008), and white women had a trend towards increased risk of liver disease progression compared with non-white women (hazard ratio, 2.84; CI, .93-8.68; P = .07). Human immunodeficiency virus/HCV-coinfected men with CD4 <200 cells/mm(3) had 2.86 times the risk of liver disease progression as HCV-monoinfected men (CI, 1.23-6.65; P = .01). Conclusions. ?Hepatitis C virus-monoinfected and HIV/HCV-coinfected drug users had high rates of clinical liver disease progression. In those with HIV infection, liver disease progression was associated with advanced immune suppression. This effect was strikingly more pronounced in women than in men.

SUBMITTER: Baranoski AS

PROVIDER: S-EPMC4777902 | biostudies-other | 2016 Jan

REPOSITORIES: biostudies-other

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Clinical Liver Disease Progression Among Hepatitis C-Infected Drug Users With CD4 Cell Count Less Than 200 Cells/mm(3) Is More Pronounced Among Women Than Men.

Baranoski Amy S AS Cotton Deborah D Heeren Timothy T Nunes David D Kubiak Rachel W RW Horsburgh C Robert CR

Open forum infectious diseases 20151231 1

Background. Hepatitis C virus (HCV) infection is a leading cause of liver-related morbidity and mortality in the United States, and injection drug users are at particularly high risk. Methods. This prospective observational cohort study assessed the rate of, and risk factors for, clinical liver disease progression in a cohort of HCV monoinfected and human immunodeficiency virus (HIV)/HCV coinfected drug users using unadjusted and multivariate Cox proportional hazards regression analyses. Resul ...[more]

PMID: 26955643

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Project description:BackgroundComplete recovery of the CD4 T cell count is uncommon among chronically HIV-infected individuals with very low pre-treatment CD4 count. We studied the prevalence of chronically immune recovery and its associated factors including immune characteristics chronic HIV-infected Thais.MethodsTreatment-naïve participants (n = 375) from the HIV-NAT 006 cohort with a pre-treatment CD4 T cell count after initiating antiretroviral therapy (ART) and having achieved a suppressed viremia (HIV-RNA level < 400 copies/mL) were retrospectively followed at the Thai Red Cross AIDS Research Centre, Bangkok, Thailand. Suboptimal immune recovery (SIR) was defined as having a CD4+ T cell count <200 cells/mm3 for 3 years after ART initiation. A case-control sub-study matched for age, sex and pre-ART CD4 T cell count was conducted to compare immunological characteristics between SIR (n = 17) and non-SIR (n = 24) participants. Immunological biomarkers such as interleukin-7 (IL-7) and soluble CD14 (sCD14) and other covariates including cytomegalovirus (CMV) DNA level, baseline hemoglobin level, hepatitis B and C co-infections, and T cell subsets associated with immune activation and exhaustion were evaluated.ResultsAmong 375 participants with pre-ART CD4 T cell counts < 200 cells/mm3, the prevalence of SIR was 39.7%, 19.7% and 7.7% at years 1, 2 and 3 after starting ART, respectively. In a multivariate analysis, a pre-ART CD4 T cell count ≤100 cells/mm3 (adjusted odds ratio [aOR] 9.45, 95% CI 2.92-30.61, p < 0.001), older age (aOR 1.07, 95% CI 1.01-1.13, p = 0.029) and baseline HIV-RNA level (aOR 0.36, 95% CI 0.21-0.59, p < 0.001) were independently associated with SIR at year 3 after ART initiation. In the matched case-control sub-study (cases = 17, controls = 24), there was a higher prevalence of hepatitis C co-infection (18.8% vs. 0%, p = 0.05), lower sCD14 levels (mean, 6.23 vs. 6.27 log10 pg/mL, p = 0.04), lower CD8 T cell counts (mean, 514 vs. 876, p = 0.0003), lower CD4/CD8 T cell ratio (mean, 0.27 vs. 0.41, p = 0.01) and higher expression of PD1 on CD8+ T cells (74.2% vs. 65.1%, p = 0.02) observed in SIR participants compared to their non-SIR counterparts at year 3 after ART initiation.ConclusionsNearly 10% of the study participants who had achieved virological suppression failed to recover a CD4 T cell count > 200 cells/mm3 after 3 years of ART which was with a very low pre-ART CD4 T cell count and older age. The long-term clinical outcomes of SIR participants need to be further explored.

Project description:BackgroundThere is conflicting evidence on the immunologic benefit of treating helminth co-infections ("deworming") in HIV-infected individuals. Several studies have documented reduced viral load and increased CD4 count in antiretroviral therapy (ART) naïve individuals after deworming. However, there are a lack of data on the effect of deworming therapy on CD4 count recovery among HIV-infected persons taking ART.Methodology/principal findingsTo estimate the association between empiric deworming therapy and CD4 count after ART initiation, we performed a retrospective observational study among HIV-infected adults on ART at a publicly operated HIV clinic in southwestern Uganda. Subjects were assigned as having received deworming if prescribed an anti-helminthic agent between 7 and 90 days before a CD4 test. To estimate the association between deworming and CD4 count, we fit multivariable regression models and analyzed predictors of CD4 count, using a time-by-interaction term with receipt or non-receipt of deworming. From 1998 to 2009, 5,379 subjects on ART attended 21,933 clinic visits at which a CD4 count was measured. Subjects received deworming prior to 668 (3%) visits. Overall, deworming was not associated with a significant difference in CD4 count in either the first year on ART (? = 42.8; 95% CI, -2.1 to 87.7) or after the first year of ART (? = ?-9.9; 95% CI, -24.1 to 4.4). However, in a sub-analysis by gender, during the first year of ART deworming was associated with a significantly greater rise in CD4 count (? = 63.0; 95% CI, 6.0 to 120.1) in females.Conclusions/significanceEmpiric deworming of HIV-infected individuals on ART conferred no significant generalized benefit on subsequent CD4 count recovery. A significant association was observed exclusively in females and during the initial year on ART. Our findings are consistent with recent studies that failed to demonstrate an immunologic advantage to empirically deworming ART-naïve individuals, but suggest that certain sub-populations may benefit.

Project description:BackgroundThalamocortical EEG rhythms in gamma (30-80 Hz) and high-gamma (80-200 Hz) ranges have been linked to arousal and conscious processes. To test the hypothesis that general anesthetics attenuate these rhythms, we characterized the concentration-effect relationship of propofol on the spectral power of these rhythms. In view of the ongoing debate about cortex versus thalamus as the primary site of anesthetic action for unconsciousness, we also compared the relative sensitivity of cortex and thalamus to this effect propofol.MethodsAdult male Long-Evans rats were chronically implanted with electrodes in somatosensory (barrel) cortex and ventroposteromedial thalamus. Propofol was delivered by a computer-controlled infusion using real-time pharmacokinetic modeling to obtain the desired plasma concentration. Spectral power was assessed during baseline, at four stable propofol plasma-concentrations (0, 3,6,9,12 ?g/ml) and during recovery over four frequency ranges (30-50, 51-75, 76-125, 126-200 Hz). Unconsciousness was defined as complete loss of righting reflex. Multiple regression was used to model the change of power (after logarithmic transformation) as a function of propofol concentration and recording site.ResultsUnconsciousness occurred at the 9 ?g/ml concentration in all animals. Propofol caused a robust linear concentration-dependent attenuation of cortical power in the 76-200 Hz range and of thalamic power in the 30-200 Hz range. In all instances the concentration-effect slope for the thalamus was markedly steeper than for the cortex. Furthermore the lowest concentration causing unconsciousness significantly reduced cortical power in the 126-200 Hz range and thalamic power in the 30-200 Hz range.ConclusionsPropofol causes a concentration-dependent attenuation of the power of thalamocortical rhythms in the 30-200 Hz range and this effect is far more pronounced for the thalamus, where the attenuation provides a robust correlate of the hypnotic action of propofol [corrected].

Project description:BackgroundCD4(+) T-lymphocyte count (CD4 count) is a standard method used to monitor HIV-infected patients during anti-retroviral therapy (ART). The World Health Organization (WHO) has pointed out or recommended that a handheld, point-of-care, reliable, and affordable CD4 count platform is urgently needed in resource-scarce settings.MethodsHIV-infected patient blood samples were tested at the point-of-care using a portable and label-free microchip CD4 count platform that we have developed. A total of 130 HIV-infected patient samples were collected that included 16 de-identified left over blood samples from Brigham and Women's Hospital (BWH), and 114 left over samples from Muhimbili University of Health and Allied Sciences (MUHAS) enrolled in the HIV and AIDS care and treatment centers in the City of Dar es Salaam, Tanzania. The two data groups from BWH and MUHAS were analyzed and compared to the commonly accepted CD4 count reference method (FACSCalibur system).ResultsThe portable, battery operated and microscope-free microchip platform developed in our laboratory (BWH) showed significant correlation in CD4 counts compared with FACSCalibur system both at BWH (r?=?0.94, p<0.01) and MUHAS (r?=?0.49, p<0.01), which was supported by the Bland-Altman methods comparison analysis. The device rapidly produced CD4 count within 10 minutes using an in-house developed automated cell counting program.ConclusionsWe obtained CD4 counts of HIV-infected patients using a portable platform which is an inexpensive (<$1 material cost) and disposable microchip that uses whole blood sample (<10 µl) without any pre-processing. The system operates without the need for antibody-based fluorescent labeling and expensive fluorescent illumination and microscope setup. This portable CD4 count platform displays agreement with the FACSCalibur results and has the potential to expand access to HIV and AIDS monitoring using fingerprick volume of whole blood and helping people who suffer from HIV and AIDS in resource-limited settings.

Dataset Information

Clinical Liver Disease Progression Among Hepatitis C-Infected Drug Users With CD4 Cell Count Less Than 200 Cells/mm(3) Is More Pronounced Among Women Than Men.

Publications

Clinical Liver Disease Progression Among Hepatitis C-Infected Drug Users With CD4 Cell Count Less Than 200 Cells/mm(3) Is More Pronounced Among Women Than Men.

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