Brygida Knysz

Decline in the AIDS and death rates in the EuroSIDA study: an observational study

BACKGROUND Since the introduction of highly active antiretroviral therapy (HAART), little is known about whether changes in HIV-1 mortality and morbidity rates have been sustained. We aimed to assess possible changes in these rates across Europe. METHODS We analysed data for 9803 patients in 70 European HIV centres including ones in Israel and Argentina. Incidence rates of AIDS or death were calculated for overall and most recent CD4 count in 6-monthly periods and in three treatment eras (pre-HAART, 1994-1995; early-HAART, 1996-1997; and late-HAART, 1998-2002). FINDINGS The incidence of AIDS or death fell after September, 1998, by 8% per 6-month period (rate ratio 0.92, 95% CI 0.88-0.95, p<0.0001). When AIDS and death were analysed separately, the incidence of all deaths during the late-HAART era was significantly lower than that during the early-HAART era in patients whose latest CD4 count was 20 cells/microL or less (0.43, 0.35-0.53, p<0.0001), but at higher CD4 counts, did not differ between early-HAART and late-HAART. Incidence of AIDS was about 50% lower in late-HAART than in early-HAART, irrespective of latest CD4 count (p<0.0001). In multivariate Coxs models, with early-HAART as the reference, there was an increased risk of AIDS (relative hazard 1.39; 95% CI 1.16-1.67, p=0.0004) and all deaths (1.29; 1.08-1.56, p=0.0065) in the pre-HAART era, and a reduced risk of AIDS (0.62; 0.50-0.77, p<0.0001) and all deaths (0.66; 0.53-0.82, p=0.0002) in the late-HAART era. INTERPRETATION The initial drop in mortality and morbidity after the introduction of HAART has been sustained. Potential long-term adverse effects associated with HAART have not altered its effectiveness in treating AIDS.

Spontaneous Viral Clearance, Viral Load, and Genotype Distribution of Hepatitis C Virus (HCV) in HIV-Infected Patients with Anti-HCV Antibodies in Europe

BACKGROUND Variables influencing serum hepatitis C virus (HCV) RNA levels and genotype distribution in individuals with human immunodeficiency virus (HIV) infection are not well known, nor are factors determining spontaneous clearance after exposure to HCV in this population. METHODS All HCV antibody (Ab)-positive patients with HIV infection in the EuroSIDA cohort who had stored samples were tested for serum HCV RNA, and HCV genotyping was done for subjects with viremia. Logistic regression was used to identify variables associated with spontaneous HCV clearance and HCV genotype 1. RESULTS Of 1940 HCV Ab-positive patients, 1496 (77%) were serum HCV RNA positive. Injection drug users (IDUs) were less likely to have spontaneously cleared HCV than were homosexual men (20% vs. 39%; adjusted odds ratio [aOR], 0.36 [95% confidence interval {CI}, 0.24-0.53]), whereas patients positive for hepatitis B surface antigen (HBsAg) were more likely to have spontaneously cleared HCV than were those negative for HBsAg (43% vs. 21%; aOR, 2.91 [95% CI, 1.94-4.38]). Of patients with HCV viremia, 786 (53%) carried HCV genotype 1, and 53 (4%), 440 (29%), and 217 (15%) carried HCV genotype 2, 3, and 4, respectively. A greater HCV RNA level was associated with a greater chance of being infected with HCV genotype 1 (aOR, 1.60 per 1 log higher [95% CI, 1.36-1.88]). CONCLUSIONS More than three-quarters of the HIV- and HCV Ab-positive patients in EuroSIDA showed active HCV replication. Viremia was more frequent in IDUs and, conversely, was less common in HBsAg-positive patients. Of the patients with HCV viremia analyzed, 53% were found to carry HCV genotype 1, and this genotype was associated with greater serum HCV RNA levels.

Changes in hospital admissions across Europe: 1995-2003. Results from the EuroSIDA study

To describe changes in the proportions of patients admitted to hospital and the duration of admission during the month of March between 1995 and 2003 and to describe the factors related to admission for 9802 patients from EuroSIDA, a pan‐European, observational cohort study.

Regional changes over time in initial virologic response rates to combination antiretroviral therapy across Europe.

Background: Changes in virologic response to initial combination antiretroviral therapy (cART) over calendar time may indicate improvements in cART or emergence of primary resistance. Regional variations may identify differences in available antiretroviral drugs or patient management. Methods: Virologic response (viral load < 500 copies/mL) 6 to 12 months after starting cART was analyzed in antiretroviral-naive EuroSIDA patients. Analyses were stratified by region (south, central west, north, east) or time started cART (early, 1996-1997; mid, 1998-1999; late, 2000-1904). Results: Virologic suppression was achieved by 60% of 2102 patients: 57% south (n = 560), 61% central west (n = 466), 63% north (n = 606), 58% east (n = 470) (P = 0.091). An increase was observed over time: 52% early cART, 56% mid cART, 69% late cART (P < 0.001). Overall, there were significant effects of region (P = 0.026) and time (P < 0.001) on virologic response after adjustment for confounders. Stratified by period, regional differences were less evident (early cART, P = 0.967; mid cART, P = 0.291; late cART, P = 0.163). Stratified by region, temporal changes were observed (south, P = 0.061; central west, P < 0.001; north: P = 0.070; east, P = 0.001). Conclusions: There was some evidence of regional differences in initial virologic response to cART. Improvements over time were observed, suggesting that so far, the effect of primary resistance has not been of sufficient magnitude to prevent increasing suppression rates.

Evaluation of early cerebral metabolic, perfusion and microstructural changes in HCV-positive patients: a pilot study.

BACKGROUND & AIMS The aim of the study was to evaluate early metabolic perfusion, and microstructural cerebral changes in patients with the hepatitis C virus (HCV) infection and normal appearing brain on plain MR using advanced MR techniques, as well as to assess correlations of MR measurements with the liver histology activity index (HAI). METHODS Fifteen HCV-positive patients and 18 control subjects underwent single voxel MR spectroscopy (MRS), perfusion weighted imaging (PWI), and diffusion tensor imaging (DTI), using a 1.5T MR unit. MRS metabolite ratios (NAA/Cr, Cho/Cr, mI/Cr) were calculated. PWI values of relative cerebral blood volume (rCBV) were assessed from 8 areas including several cortical locations, basal ganglia, and fronto-parietal white matter. DTI fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were obtained from 14 white matter tracts. RESULTS Compared to controls, HCV-positive patients showed significantly (p < 0.05) lower NAA/Cr ratios within frontal and parietal white matters, lower rCBV values within frontal and temporo-parietal cortices, decreased FA values, as well as increased ADC values in several white matter tracts. We also found elevated rCBV values in basal ganglia regions. The increase in mI/Cr and Cho/Cr ratio was correlated with a higher HAI score. CONCLUSIONS The results of advanced MR techniques indicate neurotoxicity of HCV reflected by neuronal impairment within white matter, cortical hypoperfusion, and disintegrity within several white matter tracts. Hyperperfusion in basal ganglia may be an indicator of brain inflammation in HCV patients. Our findings may suggest a biologic link between HCV-related liver disease and cerebral dysfunction.

Efficacy and safety of ombitasvir/paritaprevir/r and dasabuvir compared to IFN-containing regimens in genotype 1 HCV patients: The MALACHITE-I/II trials

BACKGROUND & AIMS Telaprevir plus pegylated interferon/ribavirin (TPV+PegIFN/RBV) remains a therapeutic option for chronic hepatitis C virus (HCV) genotype (GT) 1 infection in many regions. We conducted two open-label, phase IIIb trials comparing safety and efficacy of all-oral ombitasvir/paritaprevir/ritonavir and dasabuvir±ribavirin (OBV/PTV/r+DSV±RBV) and TPV+PegIFN/RBV. METHODS Treatment-naïve (MALACHITE-I) or PegIFN/RBV-experienced (MALACHITE-II) non-cirrhotic, chronic HCV GT1-infected patients were randomized to OBV/PTV/r+DSV+weight-based RBV, OBV/PTV/r+DSV (treatment-naïve, GT1b-infected patients only), or 12weeks of TPV+PegIFN+weight-based RBV and 12-36 additional weeks of PegIFN/RBV. The primary endpoint was sustained virologic response 12weeks post-treatment (SVR12). Patient-reported outcome questionnaires evaluated mental and physical health during the studies. RESULTS Three hundred eleven treatment-naïve and 148 treatment-experienced patients were randomized and dosed. Among treatment-naïve patients, SVR12 rates were 97% (67/69) and 82% (28/34), respectively, in OBV/PTV/r+DSV+RBV and TPV+PegIFN/RBV-treated GT1a-infected patients; SVR12 rates were 99% (83/84), 98% (81/83), and 78% (32/41) in OBV/PTV/r+DSV+RBV, OBV/PTV/r+DSV, and TPV+PegIFN/RBV-treated GT1b-infected patients. Among treatment-experienced patients, SVR12 rates were 99% (100/101) and 66% (31/47) with OBV/PTV/r+DSV+RBV and TPV+PegIFN/RBV. Mental and physical health were generally better with OBV/PTV/r+DSV±RBV than TPV+PegIFN/RBV. Rates of discontinuation due to adverse events (0-1% and 8-11%, respectively, p<0.05) and rates of hemoglobin decline to <10g/dl (0-4% and 34-47%, respectively, p<0.05) were lower for OBV/PTV/r+DSV±RBV than TPV+PegIFN/RBV. CONCLUSIONS Among non-cirrhotic, HCV GT1-infected patients, SVR12 rates were 97-99% with 12week, multi-targeted OBV/PTV/r+DSV±RBV regimens and 66-82% with 24-48 total weeks of TPV+PegIFN/RBV. OBV/PTV/r+DSV±RBV was associated with a generally better mental and physical health, more favorable tolerability, and lower rates of treatment discontinuation due to adverse events.

Evaluation of metabolic changes within the normal appearing gray and white matters in neurologically asymptomatic HIV-1-positive and HCV-positive patients: Magnetic resonance spectroscopy and immunologic correlation

OBJECTIVE The aim of the study was to evaluate early metabolic changes using proton MR spectroscopy (MRS) in asymptomatic HIV-1-positive and HCV-positive patients without abnormalities in the structural MR examination. METHODS Sixty-five asymptomatic patients: 21 HIV-1-positive naive, 20 HIV-1-positive with combination antiretroviral therapy (cART), 9 HIV-1/HCV-positive naive, 15 HCV-positive naive and 18 normal subjects were enrolled in the study. The MRS examinations were performed with a 1.5T MR scanner. Voxels were located in the following regions: posterior cingulate gyrus (PCG), anterior cingulate gyrus (ACG), parietal white matter (PWM), left basal ganglia (BG) and frontal white matter (FWM). The NAA/Cr, Cho/Cr, mI/Cr ratios and correlations of MRS measurements with the immunologic data were analyzed. RESULTS There was a significant decrease (p<0.05) of the NAA/Cr ratios in PCG, ACG and PWM regions in HIV-1-positive cART treated patients compared to the normal subjects. The significantly decreased NAA/Cr ratios in PWM and FWM were observed in HCV infected patients. The subjects with HIV-1/HCV co-infection revealed significantly lower NAA/Cr ratios in the ACG area. Other metabolite ratios in all analyzed regions, as well as the NAA/Cr ratios in BG showed no significant differences. The decrease of CD4n T cell count was associated with the decease of the NAA/Cr ratio in the PCG area and the increase of Cho/Cr ratio in the FWM region. CONCLUSIONS The metabolic changes - reduction of NAA/Cr ratios are most pronounced in HIV-1-positive patients using cART. The low CD4n T cell count is a risk factor for neurocognitive impairment in HIV-1-positive patients.

Value of Perfusion-Weighted MR Imaging in the Assessment of Early Cerebral Alterations in Neurologically Asymptomatic HIV-1-Positive and HCV-Positive Patients

Background and Purpose Asymptomatic central nervous system (CNS) involvement occurs in the early stage of the human immunodeficiency virus (HIV) infection. It has been documented that the hepatitis C virus (HCV) can replicate in the CNS. The aim of the study was to evaluate early disturbances in cerebral microcirculation using magnetic resonance (MR) perfusion-weighted imaging (PWI) in asymptomatic HIV-1-positive and HCV-positive patients, as well as to assess the correlation between PWI measurements and the clinical data. Materials and Methods Fifty-six patients: 17 HIV-1-positive non-treated, 18 HIV-1-positive treated with combination antiretroviral therapy (cART), 7 HIV-1/HCV-positive non-treated, 14 HCV-positive before antiviral therapy and 18 control subjects were enrolled in the study. PWI was performed with a 1.5T MR unit using dynamic susceptibility contrast (DSC) method. Cerebral blood volume (CBV) measurements relative to cerebellum (rCBV) were evaluated in the posterior cingulated region (PCG), basal ganglia (BG), temporoparietal (TPC) and frontal cortices (FC), as well as in white matter of frontoparietal areas. Correlations of rCBV values with immunologic data and liver histology activity index (HAI) were analyzed. Results Significantly lower rCBV values were found in the right TPC and left FC as well as in PCG in HIV-1-positive naïve (p = 0.009; p = 0.020; p = 0.012), HIV-1 cART treated (p = 0.007; p = 0.009; p = 0.033), HIV-1/HCV-positive (p = 0.007; p = 0.027; p = 0.045) and HCV-positive patients (p = 0.010; p = 0.005; p = 0.045) compared to controls. HIV-1-positive cART treated and HIV-1/HCV-positive patients demonstrated lower rCBV values in the right FC (p = 0.009; p = 0.032, respectively) and the left TPC (p = 0.036; p = 0.005, respectively), while HCV-positive subjects revealed lower rCBV values in the left TPC region (p = 0.003). We found significantly elevated rCBV values in BG in HCV-positive patients (p = 0.0002; p<0.0001) compared to controls as well as to all HIV-1-positive subjects. There were no significant correlations of rCBV values and CD4 T cell count or HAI score. Conclusions PWI examination enables the assessment of HIV-related as well as HCV-related early cerebral dysfunction in asymptomatic subjects. HCV-infected patients seem to reveal the most pronounced perfusion changes.

Prevalence of Demodex spp. in eyelash follicles in different populations

Introduction The pathologic relevance of Demodex infestation in blepharitis is still controversial. The aim of the study was to determine the prevalence of Demodex spp. in eyelash follicles and its relationship to eye symptoms. Material and methods A total of 290 individuals were studied for the presence of Demodex folliculorum and Demodex brevis within eyelash follicles. Participants belonged to one of four groups: inpatients, drug abusers, health professionals, and medical students. Ten eyelashes were epilated from each subject, placed on microscope slides and examined for parasites. The sample was defined as positive if at least one parasite or parasites ova were present. The presence of parasites was analyzed according to age, gender, place of living, reported eye problems, and use of contact lenses or glasses. Results The prevalence of Demodex spp. infestation among all studied subjects was 41%, with the highest infestation rate among inpatients (p < 0.01) and elderly people (p < 0.001). No difference regarding the presence of Demodex was found between women and men (p = 0.76). Demodex folliculorum was about 2.4 times more frequent than D. brevis. The prevalence of Demodex spp. in subjects with and without eye complaints suggesting blepharitis was similar (41.6% vs. 40.2%, respectively, p = 0.9). On the other hand, wearing glasses was linked to Demodex infestation (48.4% vs. 32.3%, p < 0.01). Conclusions Demodex is a common saprophyte found in human eyelash follicles. Its presence might be related to some ocular discomfort; however, in the vast majority of cases the infestation seems to be asymptomatic.

Vitamin D and clinical disease progression in HIV infection: results from the EuroSIDA study

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK