HIV Markers Research Articles

A pilot study of brisk walking in sedentary combination antiretroviral treatment (cART)- treated patients: benefit on soluble and cell inflammatory markers

BackgroundChronic HIV infection is associated with low-level inflammation and increased risk of chronic diseases and mortality. The objective was to assess the effects of moderate intensity exercise on metabolic and inflammatory markers in HIV-infected treated persons.MethodsThis was a pilot study enrolling cART-treated, sedentary persons with metabolic complications in a 12-week protocol, consisting of three sessions per week of 60 min brisk walking with (strength-walk group) or without (walk group) 30 min circuit-training. Assessments at baseline and week 12 (W12) included body morphometrics and total body dual-energy X-ray absorptiometry; lipid and glucose blood profile; plasma level of high sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), D-dimer, interleukin-18 (IL-18), soluble CD14, and CD38 and HLA-DR expression on CD4+ and CD8+ T-cells.ResultsForty-nine patients were included and 35 (71%) completed the program: 21 in the walk and 14 in the strength-walk group. At W12, significant improvements were observed of body mass index, waist and hip circumference, and total cholesterol both overall and in the walk group, and of LDL cholesterol in both training groups. In the whole group, significant reductions were observed in hsCRP, IL-6, D-dimer, IL-18, and of CD8+/CD38+/HLA-DR+ cell frequencies. HsCRP and CD8+/CD38+/HLA-DR+ frequency decreased significantly in both training groups when examined separately whereas IL-6 and D-dimer in the walk group only.ConclusionsBrisk walking, with or without strength exercise, could improve lipid profile and inflammatory markers in chronic HIV infection.Trial registrationACTRN12615001258549, registered 17 November 2015, “retrospectively registered” Web address of trial: http://www.ANZCTR.org.au/ACTRN12615001258549.aspx

Evolution of hepatitis B serological markers in HIV coinfected patients: a case study.

ABSTRACTOBJECTIVE To describe the evolution of serological markers among HIV and hepatitis B coinfected patients, with emphasis on evaluating the reactivation or seroreversion of these markers.METHODS The study population consisted of patients met in an AIDS Outpatient Clinic in São Paulo State, Brazil. We included in the analysis all HIV-infected and who underwent at least two positive hepatitis B surface antigen serological testing during clinical follow up, with tests taken six months apart. Patients were tested with commercial kits available for hepatitis B serological markers by microparticle enzyme immunoassay. Clinical variables were collected: age, sex, CD4+ T-cell count, HIV viral load, alanine aminotransferase level, exposure to antiretroviral drugs including lamivudine and/or tenofovir.RESULTS Among 2,242 HIV positive patients, we identified 105 (4.7%) patients with chronic hepatitis B. Follow up time for these patients varied from six months to 20.5 years. All patients underwent antiretroviral therapy during follow-up. Among patients with chronic hepatitis B, 58% were hepatitis B “e” antigen positive at the first assessment. Clearance of hepatitis B surface antigen occurred in 15% (16/105) of patients with chronic hepatitis B, and 50% (8/16) of these patients presented subsequent reactivation or seroreversion of hepatitis B surface antigen. Among hepatitis B “e” antigen positive patients, 57% (35/61) presented clearance of this serologic marker. During clinical follow up, 28.5% (10/35) of those who initially cleared hepatitis B “e” antigen presented seroreversion or reactivation of this marker.CONCLUSIONS Among HIV coinfected patients under antiretroviral therapy, changes of HBV serological markers were frequently observed. These results suggest that frequent monitoring of these serum markers should be recommended.

Correlates of infection and molecular characterization of blood-borne HIV, HCV, and HBV infections in HIV-1 infected inmates in Italy: An observational cross-sectional study.

Coinfection of blood-borne hepatitis B and hepatitis C viruses (HBV and HCV, respectively) in human immunodeficiency virus type 1 (HIV-1)-positive individuals frequently occurs in inmate population and peculiar viral strains and patterns of virological markers may be observed.Plasma from 69 HIV-1-positive inmates was obtained from 7 clinical centers connected with correctional centers in different towns in Italy. HIV, HBV, and HCV markers were tested by commercial assays. Virus genotyping was carried out by sequencing the protease and reverse transcriptase-encoding region (PR-RT region) for HIV and a region encompassing the NS5B gene for HCV and subsequent phylogenetic analysis.Twelve over 14 HIV-subtyped inmates were infected with HIV-1 subtype B strains. The 2 non-B strains belonged to subtype G and CRF02_AG, in an Italian and a Gambian patient, respectively. Variants carrying the K103N and Y181C resistance mutations to non-nucleoside reverse transcriptase inhibitors (NNRTIs) were found in 2 out of 9 patients naive for combined antiretroviral therapy (cART) (22.2%). Most HIV-positive patients (92.8%) showed evidence of past or present HBV and/or HCV infection. Prevalence of HBV and HCV was 81.2% for both viruses, whereas prevalence of HBV/HCV coinfection was 69.6%. A significantly higher presence of HCV infection was found in Italians [odds ratio (OR) 11.0; interval 1.7–80.9] and in drug users (OR 27.8; interval 4.9–186.0). HCV subtypes were determined in 42 HCV or HBV/HCV-coinfected individuals. HCV subtypes 1a, 3a, 4d, and 1b were found in 42.9%, 40.5%, 14.3%, and 2.4% of inmates, respectively. Low titers of HBV DNA in HBV DNA positive subjects precluded HBV subtyping.The high prevalence of HBV and HCV coinfections in HIV-infected inmates, as well as the heterogeneity of HIV and HCV subtypes suggest the need to adopt systematic controls in prisons to monitor both the burden and the genetic forms of blood-borne viral infections, in order to apply targeted therapeutic interventions.

The role of trophoblast cell receptor expression in HIV-1 passage across the placenta in pre-eclampsia: an observational study.

To compare expression of markers of HIV and associated receptors (p24, CD4, CCR5 and ICAM-2) in placentae and umbilical cords of HIV-associated and pre-eclamptic pregnancies to elucidate any association between these conditions in mother-to-child transmission. Cross-sectional immunohistochemical analysis of target receptor expression. Laboratory-based study of primigravidae attending a district hospital in South Africa. Retrospectively collected placental tissue (stratified into four groups according to HIV status of normotensive and pre-eclamptic participants (n=20/group). Immunohistochemistry utilising CD4 (1:1), p24 (1:10), CCR5 (1:80) and ICAM-2 (1:100) antibodies was performed using light microscopy for image acquisition and analysis. Evaluate the expression of receptors on syncytiotrophoblast involved in in utero transmission of HIV. Syncytiotrophoblast was immunopositive for CD4 and CCR5 antibody with greater expression of CCR5 in HIV-positive versus HIV-negative groups (F1,159 =6.979, P=0.009) and normotensive versus pre-eclamptic groups (F1,159 =8.803, P=0.003). p24 was present in both placentae and umbilical cords of babies that were HIV-negative at 6weeks. ICAM-2 immunostaining was observed in the syncytiotrophoblast across study groups and was significantly higher in the HIV-negative pre-eclamptic group (χ2 (3) =45.3; P<0.001). Concurrent CD4 and CCR5 receptor expression demonstrates possible in utero viral entry routes across the placental barrier. ICAM-2 expression may influence HIV passage across the placenta or restoration of risk of pre-eclampsia in HAART-treated mothers. HIV was found in fetal circulation regardless of antiretroviral treatment. Further confirmatory ultrastructural and molecular work is warranted. CD4, CCR5 and ICAM-2 on syncytiotrophoblast may facilitate HIV infection of passage across the placenta.

High variability of HIV and HCV seroprevalence and risk behaviours among people who inject drugs: results from a cross-sectional study using respondent-driven sampling in eight German cities (2011-14).

BackgroundPeople who inject drugs (PWID) are at increased risk of acquiring and transmitting HIV and Hepatitis C (HCV) due to sharing injection paraphernalia and unprotected sex. To generate seroprevalence data on HIV and HCV among PWID and related data on risk behaviour, a multicentre sero- and behavioural survey using respondent driven sampling (RDS) was conducted in eight German cities between 2011 and 2014. We also evaluated the feasibility and effectiveness of RDS for recruiting PWID in the study cities.MethodsEligible for participation were people who had injected drugs within the last 12 months, were 16 years or older, and who consumed in one of the study cities. Participants were recruited, using low-threshold drop-in facilities as study sites. Initial seeds were selected to represent various sub-groups of people who inject drugs (PWID). Participants completed a face-to-face interview with a structured questionnaire about socio-demographics, sexual and injecting risk behaviours, as well as the utilisation of health services. Capillary blood samples were collected as dried blood spots and were anonymously tested for serological and molecular markers of HIV and HCV. The results are shown as range of proportions (min. and max. values (%)) in the respective study cities. For evaluation of the sampling method we applied criteria from the STROBE guidelines.ResultsOverall, 2,077 PWID were recruited. The range of age medians was 29–41 years, 18.5–35.3 % of participants were female, and 9.2–30.6 % were foreign born. Median time span since first injection were 10–18 years. Injecting during the last 30 days was reported by 76.0–88.4 % of participants. Sharing needle/syringes (last 30 days) ranged between 4.7 and 22.3 %, while sharing unsterile paraphernalia (spoon, filter, water, last 30 days) was reported by 33.0–43.8 %. A majority of participants (72.8–85.8 %) reported incarceration at least once, and 17.8–39.8 % had injected while incarcerated. Between 30.8 and 66.2 % were currently in opioid substitution therapy. Unweighted HIV seroprevalence ranged from 0–9.1 %, HCV from 42.3–75.0 %, and HCV-RNA from 23.1–54.0 %. The implementation of RDS as a recruiting method in cooperation with low-threshold drop in facilities was well accepted by both staff and PWID. We reached our targeted sample size in seven of eight cities.ConclusionsIn the recruited sample of mostly current injectors with a long duration of injecting drug use, seroprevalence for HIV and HCV varied greatly between the city samples. HCV was endemic among participants in all city samples. Our results demonstrate the necessity of intensified prevention strategies for blood-borne infections among PWID in Germany.Electronic supplementary materialThe online version of this article (doi:10.1186/s12889-016-3545-4) contains supplementary material, which is available to authorized users.

Risk Factors Associated With Quantitative Evidence of Lung Emphysema and Fibrosis in an HIV-Infected Cohort.

The disease spectrum for HIV-infected individuals has shifted toward comorbid non-AIDS conditions including chronic lung disease, but quantitative image analysis of lung disease has not been performed. To quantify the prevalence of structural changes of the lung indicating emphysema or fibrosis on radiographic examination. A cross-sectional analysis of 510 HIV-infected participants in the multicenter Lung-HIV study was performed. Data collected included demographics, biological markers of HIV, pulmonary function testing, and chest computed tomographic examinations. Emphysema and fibrosis-like changes were quantified on computed tomographic images based on threshold approaches. In our cohort, 69% was on antiretroviral therapy, 13% had a current CD4 cell count less than 200 cells per microliter, 39% had an HIV viral load greater than 500 copies per milliliter, and 25% had at least a trace level of emphysema (defined as >2.5% of voxels <-950HU). Trace emphysema was significantly correlated with age, smoking, and pulmonary function. Neither current CD4 cell count nor HIV viral load was significantly correlated with emphysema. Fibrosis-like changes were detected in 29% of the participants and were significantly correlated with HIV viral load (Pearson correlation coefficient = 0.210; P < 0.05); current CD4 cell count was not associated with fibrosis. In multivariable analyses including age, race, and smoking status, HIV viral load remained significantly correlated with fibrosis-like changes (coefficient = 0.107; P = 0.03). A higher HIV viral load was significantly associated with fibrosis-like changes, possibly indicating early interstitial lung disease, but emphysematous changes were not related to current CD4 cell count or HIV viral load.

Viral markers for HIV cure trials: are we getting any closer?

The definite proof of concept of an effective treatment aimed at HIV cure would be a very prolonged or permanent HIV remission after interruption of treatment. However, treatment interruption studies have generally resulted in a quick viral rebound in nearly all patients with the exception of a few isolated cases of long-term post-treatment control. Consequently, biomarkers that could predict whether a cure strategy has any profound impact are needed [1].

Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) Co-Infection Among HIV Infected Individuals at Tertiary Care Hospital in Western Nepal.

The HIV, HBV and HCV viruses are the major public health concern all over the world including Nepal. The aim of the study is to determine the rate of HBV and HCV co-infections in patients with HIV infection. The study cohort included 218 consecutive HIV infected patients who were examined for co-infection with HBV or HCV or both at Manipal teaching hospital, Western Nepal. The demographic data of the subjects was collected retrospectively. The data was analyzed with SPSS software and EPI Info to measure the correlation of variables and infection rates. In the course of six years study period, a total of 25,708 samples were collected for HIV screening test. The 218 (0.8%) screen test positive for HIV were confirmed as per WHO guidelines. The overall rate of co-infection with HBV and or HCV was 7.3% (16 of 218 patients). Only 7 (3.2% [CI 1.3, 6.5]) were positive for both HIV and HBV infection markers and 9 (4.1% [CI 1.9, 7.7]) were positive for HIV and HCV infection markers. None were positive of all three virus markers. It is advisable to implementregular screening for Hepatitis B Virus and Hepatitis C Virus among all HIV infected individuals and their sexual partners.

1C.01

Objective: Elevated inflammatory markers such as C-reactive protein (CRP) and interleukin-6 (IL-6) are well-known risk factors for cardiovascular mortality. The less familiar marker, soluble urokinase plasminogen activator receptor (suPAR), is known to predict cancer, infections and all-cause mortality. We determined whether suPAR, CRP and IL-6 are predictive of both all-cause and cardiovascular mortality in a black population, highly burdened by cardiovascular disease and HIV infection. Design and method: We included 1 425 black South Africans, of which 208 died within five years after baseline data collection. EDTA plasma biomarker levels were determined, while all-cause and cardiovascular mortality were used as endpoints. Results: At baseline suPAR, CRP and IL-6 were higher in non-survivors than in survivors (P < 0.001). SuPAR (HR 1.27, 95% CI 1.09–1.48), IL-6 (HR 1.49, 95% CI 1.24–1.78) and CRP (HR 1.39, 95% CI 1.17–1.65) predicted all-cause mortality, while only suPAR (HR 1.40, 95% CI 1.04–1.87) and IL-6 (HR 1.61, 95% CI 1.10–2.35) predicted cardiovascular mortality. The prognostic value of suPAR was independent of IL-6 and CRP (P<=0.015).Conclusions: SuPAR predicted both all-cause and cardiovascular mortality, independent of traditional risk factors, HIV and other inflammatory markers, underlining the prognostic value of suPAR in a black population.

Soluble urokinase plasminogen activator receptor as a prognostic marker of all-cause and cardiovascular mortality in a black population

BackgroundElevated inflammatory markers such as C-reactive protein (CRP) and interleukin-6 (IL-6) are well-known risk factors for cardiovascular mortality. The less familiar marker, soluble urokinase plasminogen activator receptor (suPAR), is known to predict cancer, infections and all-cause mortality. We determined whether suPAR, CRP and IL-6 are predictive of both all-cause and cardiovascular mortality in a black population, highly burdened by cardiovascular disease and HIV infection. MethodsWe included 1425 black South Africans, of which 208 died within five years after baseline data collection. EDTA plasma biomarker levels were determined, while all-cause and cardiovascular mortality were used as endpoints. ResultsAt baseline suPAR, CRP and IL-6 were higher in non-survivors than in survivors (P<0.001). SuPAR (HR 1.27, 95% CI 1.09–1.48), IL-6 (HR 1.49, 95% CI 1.24–1.78) and CRP (HR 1.39, 95% CI 1.17–1.65) predicted all-cause mortality, while only suPAR (HR 1.40, 95% CI 1.04–1.87) and IL-6 (HR 1.61, 95% CI 1.10–2.35) predicted cardiovascular mortality. The prognostic value of suPAR was independent of IL-6 and CRP (P≤0.015). ConclusionSuPAR predicted both all-cause and cardiovascular mortality, independent of traditional risk factors, HIV and other inflammatory markers, underlining the prognostic value of suPAR in a black population.

Immuno-hematological abnormalities of human immunodeficiency virus-1 infected highly active antiretroviral naïve adults in Zaria, Northern Nigeria

Background: In HIV-1-infected adults, hematological derangements include peripheral cytopenias and bone marrow abnormalities. The level of the CD4+ T lymphopenia is presently considered as one of the best markers of HIV induced immune impairment. Multiple interacting factors contribute to the hematological manifestations of HIV infection. We compare the prevalence of peripheral cytopenias and the level of immunological deterioration in treatment naive HIV-1 infected patients. Patients and Methods: Four hundred consecutive HIV-1 infected patients undergoing pre-treatment (Highly active antiretroviral therapy naive) assessment were recruited at the HIV sub-specialty clinic of Ahmadu Bello University Teaching Hospital, Zaria, Nigeria between May 2003 and October 2004. A cross-sectional study of baseline hematological and immunological parameters was undertaken after confirmation of HIV-1 infection by double ELISA methods; complete blood count and CD4+ T cell count (Dynal ® ) were analyzed by manual techniques. Results: Anemia is the most common peripheral cytopenia, 73% in male and 54% in the females. Neutropenia occurred in 10.8% of the patients while 6.25% had thrombocytopenia. Packed cell volume and Absolute lymphocyte count is associated with a reduction of CD4+ T cell counts but this is not consistent following gender and CDC clinical/immunological staging. CD4+ T cell counts decreases significant from asymptomatic stage A through symptomatic stages B to stage C p Conclusion: This study demonstrates that anemia and low CD4+ T cells are the commonest hematological complication in HIV-1 infected patients and these cytopenias deteriorates with increasing advanced stages of the infection.

Herpes simplex virus type 2 serostatus is not associated with inflammatory or metabolic markers in antiretroviral therapy-treated HIV.

Systemic inflammation and immune activation may persist in HIV-infected persons on suppressive combination antiretroviral therapy (cART) and contribute to adverse health outcomes. We compared markers of immune activation, inflammation, and abnormal glucose and lipid metabolism in HIV-infected adults according to herpes simplex virus type 2 (HSV-2) serostatus in a 6-month observational cohort study in Toronto, Canada. HIV-infected adults on suppressive (viral load <50 copies/ml) cART were categorized as HSV-2 seropositive or seronegative using the HerpeSelect ELISA, and underwent study visits at baseline, 3 months, and 6 months. The primary outcome was the median percentage of activated (CD38(+)HLADR(+)) CD8 T cells. Secondary outcome measures included additional immune (activated CD4, regulatory T cells) and inflammatory (hsCRP, D-dimer, IL-1b, IL-6, MCP-1, TNF, sICAM-1, sVCAM-1, Ang1/Ang2 ratio) markers. Metabolic outcomes included the proportion with impaired fasting glucose/impaired glucose tolerance/diabetes, insulin sensitivity (calculated using the Matsuda index), insulin resistance (homeostasis model assessment of insulin resistance), and fasting lipids. The impact of HSV-2 on each outcome was estimated using generalized estimating equation regression models. Of 84 participants, 38 (45%) were HSV-2 seropositive. HSV signs and symptoms were uncommon. Aside from D-dimer, which was more often detectable in HSV-2 seropositives (adjusted odds ratio=3.58, 95% CI=1.27, 10.07), HSV-2 serostatus was not associated with differences in any other immune, inflammatory cytokine, acute phase reactant, endothelial activation, or metabolic markers examined in univariable or multivariable models. During the study, CD8 and CD4 T cell activation declined by 0.16% and 0.08% per month, respectively, while regulatory T cells increased by 0.05% per month. HSV-2 serostatus was not consistently associated with immune activation, inflammatory, or lipid and glucose metabolic markers in this cohort of HIV-infected adults on suppressive cART.

History of Hepatitis B Infection Is the Most Common Risk Factor Impacting Eligibility in Minority Donors for Cord Blood

▪Background:Cord blood (CB) is an accepted allogeneic hematopoietic stem cell source and has increased access to transplantation particularly for minority patients (Barker et al, BBMT 2010; 16: 1541-48). As a result, one of the aims of the CB Banks is to increase collections from minority donors.Before the acceptance of any Cord Blood Unit (CBU) in the searchable inventory for potential use in clinical transplantation, FDA requires donor eligibility assignment, as mandated by the 2005 published guidelines, and licensure.Objective and Methods:We performed a retrospective analysis of the eligibility assignment on the CBU collected during the period 4/2013-3/2014 (one fiscal year) in six collection sites of the National Cord Blood Program (NCBP) at the New York Blood Center. Three of the collection sites are located in the New York area, and the other three in each of the following states: Atlanta, GA, Cleveland, OH, and Fairfax, VA. All CBU that met criteria for banking were evaluated for eligibility; CBU with positive maternal infectious disease markers for HIV, HCV, HBV and HTLV were discarded according to the FDA Guidelines.We grouped the reasons for ineligibility in six risk factor categories, as listed in Table 1. We further looked at race/ethnic background of the mothers and the various risk factors and impact on donor eligibility.Results:From a total of 1826 CBU placed in the NCBP searchable inventory during the study period, 1597 (87%) were qualified as eligible, whereas 237 (13%) were assigned as ineligible. 1567 eligible CBU (85.5%) met all other FDA licensure criteria and became licensed HEMACORD®, whereas the ineligible CBU, or eligible with parameters below the FDA specifications were Investigational New Drug (IND) products (N=259 or 14%).Table 1Reasons for ineligibility for CBU%#1. Mother immigrated from, or lived in Europe50.6%#2. Mother with anti-HB Core reactive, HBsAg negative, HBV PCR nonreactive24.4%#3. High risk behavior in mother (incarcerated during pregnancy, etc)9.7%#4. Transfusion in pregnancy, severe autoimmune disease4.6%#5. Chorioamnionitis diagnosis in mother3.7%#6. Other (isolated events)6.75%Note: HBV PCR was performed using Procleix Ultrio assay (Gen Probe, Inc.)Abstract 2453. Table 2RaceNReason #1Reason #2Reason #3Reason #4Reason #5Reason #6White11677.5%13.7%7.75%3.45%1.72%4.3%Asian3735%54%2.7%0%2.7%5.4%African American429.5%36%19%13.5%9.5%13%Multi-race4154%17%12%4.8%4.8%7.3%Pacific Islander1100%0%0%0%0%0%Results and discussion:In our cohort of 237 ineligible CBU, the racial distribution was as follows: 49% came from White donors, 16% from Asian, 18% from African American and 17% from Multi-Race donors. The two leading causes for donor’s ineligibility in our cohort were the risk of vCJD associated with maternal immigration/extended residence in a European country, or in American military base in Europe (51% of the cases), and presence of anti-HB Core Ab with HBV DNA negative results (24.5%).The percentage of ineligible CBU within total number of donations from each individual racial group was as follows: White: 12%; Asian: 17%; African American: 11% and Multi Race: 16%. This finding is in contrast with published data where African American donors were significantly less likely to be eligible to donate whole blood (Shaz BH et al, Transfusion 2012 52(5); 1050-61). It is important to note that the presence of positive anti-HB Core Ab was the leading cause for ineligibility among Asian (54%), and African American donors (36%). None of these donors were positive for HBV DNA indicating absence of viremia.Conclusion:In contrast to blood donors, CBU from ineligible donors can be used for transplantation as IND products, rather than being deferred, provided there is an urgent medical need. History of hepatitis B infection is a common risk factor in minority donors but viremia has not been demonstrated. On the other hand, “reluctance” to use these CBU in clinical practice impacts primarily minority patients. DisclosuresNo relevant conflicts of interest to declare.

Serological markers of viral, syphilitic and toxoplasmic infection in children and teenagers with nephrotic syndrome: case series from Mato Grosso State, Brazil.

Some infections can be the cause of secondary nephrotic syndrome. The aim of this study was to describe the experience of a Renal Disease Reference Clinic from Central Brazil, in which serological markers of some infectious agents are systematically screened in children with nephrotic syndrome. Data were obtained from the assessment of medical files of all children under fifteen years of age, who matched nephrotic syndrome criteria. Subjects were tested for IgG and IgM antibodies against T. gondii and cytomegalovirus; antibodies against Herpes simplex, hepatitis C virus and HIV; and surface antigen (HBsAg) of hepatitis B virus. The VDRL test was also performed. 169 cases were studied. The median age on the first visit was 44 months and 103 (60.9%) patients were male. Anti-CMV IgG and IgM were found in 70.4% and 4.1%, respectively. IgG and IgM against Toxoplasma gondii were present in 32.5% and 5.3%, respectively. Two patients were positive for HBsAg, but none showed markers for HIV, hepatitis C, or Treponema pallidum. IgG and IgM against herpes simplex virus were performed on 54 patients, of which 48.1% and 22.2% were positive. IgM antibodies in some children with clinical signs of recent infection suggest that these diseases may play a role in the genesis of nephrotic syndrome.

Glyburide-Induced Cholestatic Hepatitis

Introduction: Glyburide is a second generation sulfonylurea commonly used in the treatment of type 2 diabetes mellitus. The most common side effects include hypoglycemia, gastrointestinal disturbances, rashes, and nocturia with rare reports of hepatotoxic effects of glyburide - hepatic cholestasis, granulomatous hepatitis, and liver failure. Approximately 1% of drug-induced liver disease is caused by sulfonylurea derivatives, which are either predominately parenchymal or cholestatic in nature. Early recognition of an idiosyncratic drug reaction to glyburide is essential to prevent the reversible hepatic injury. We hereby present a case of a 35-year-old female with a past medial history significant for polycystic ovarian syndrome who presented to the primary care clinic with fever and malaise for 10 days, which was unrelieved by a 1-week course of Keflex. She was also found to have elevated blood glucose levels of 319 mg/dL and A1c of 10.2%. She was started on glyburide. After the first dose, the patient developed nausea and vomiting. Lab work done at the urgent care was significant for deranged liver function tests, prompting the admission to the hospital. On initial exam, the vitals were significant for pulse 112/min, blood pressure 103/60 mm Hg, and temperature 100.8 F. Physical exam was significant for mild abdominal distention with no tenderness to palpation. Labs revealed WBC-15.3 K/uL, hemoglobin/Hematocrit 12.5 g/dL/35.8 %, a cholestatic pattern with total bilirubin 1.9 mg/dL, alkaline phosphatase 286 U/L, AST 56 U/L, and ALT 73U/L. Viral hepatitis panel and HIV markers were unremarkable. Anti-mitochondrial antibody, smooth muscle antibody, myeloperoxidase antibody, and anti-neutrophilic antibody were negative. Ultrasound and computed tomography scan ruled out any evidence of obstruction. Hepatobiliary iminodiacetic acid scan was also negative for any signs of cholecystitis or obstruction. Based on imaging and clinical presentation, diagnosis of an idiosyncratic reaction to glyburide resulting in cholestasis was established. The patient stopped glyburide and initiated insulin for glucose control, leading to resolution of symptoms and improvement of the liver functions. On 2 weeks’ follow-up, there was normalization of liver enzymes. After the detailed discussion, the patient was agreeable to take the drug re-challenge, which confirmed the glyburide-induced cholestatic pattern of liver injury on re-exposure.

Factors associated with short-term changes in HIV viral load and CD4+ cell count in antiretroviral-naive individuals

Objectives:Among antiretroviral therapy (ART)-naive individuals, viral load levels tend to increase and CD4+ cell counts decline over time. We sought to explore the rate of change and influence of other factors associated with these markers of HIV progression.Design:An observational cohort collaboration study.Methods:A total of 158 385 pairs of consecutive viral load and CD4+ cell count simultaneously measured from 34 384 ART-naive individuals in the COHERE database were analysed. Annual changes and factors associated with these changes were estimated using generalized estimating equations.Results:Viral load continued to rise at a mean [95% confidence interval (CI)] rate of 0.091 (0.086–0.096) log10 copies/ml per year. A faster rise in viral load was significantly associated with older age, such that for every 10 years older, it was a mean 0.022 log10 copies/ml per year greater. The mean (95% CI) CD4+ cell count change was −78.0 (−80.1 to −76.0) cell/μl per year and it was strongly associated with a higher current viral load: for every 1 log10 copies/ml higher, CD4+ cell count declined by an additional 37.6 cells/μl per year (P < 0.001). Current viral load was a stronger predictor of CD4+ cell count depletion than baseline viral load. Neither sex, race nor transmission by injecting drug use was associated with change in either the viral load or CD4+ cell count.Discussion:We found that in ART-naive individuals, viral load continues to increase over time and more sharply in those who are older. Our results also suggest that higher current viral load is strongly associated with ongoing rate of CD4+ cell count depletion.

Cerebral toxoplasmosis in children and adolescents from “Dr. Victor Babeş” Hospital pediatric HIV-cohort

Cerebral toxoplasmosis (Toxo) is rarely described in children. The Romanian pediatric cohort consists of children that have been infected parenterally in the late ’80s. We aimed to describe the prevalence, clinical findings and outcome of Toxo in children and adolescents from the Romanian Pediatric Cohort, that have been diagnosed in the “Dr. Victor Babes” Hospital, one of the main reference centers for HIV from Romania Cerebral toxoplasmosis was diagnosed based on CDC case definition (presumptive and definitive diagnosis). We reviewed retrospectively the charts of all 29 children diagnosed with Toxo starting 1996, recording the demographic, HIV markers, antiretroviral treatment, clinical and neuroimaging data, treatment and outcome of Toxo. The prevalence of Toxo was 4.8% from 604 patients followed in the Hospital. Out of 29 patients diagnosed with Toxo, 19 were girls and 28 had parenterally and 1 had vertically acquired HIV. The mean age at HIV diagnosis was 11.5±6.5 years, and 15.6±5.3 years at Toxo diagnosis. In 10 patients HIV was diagnosed concomitantly with Toxo. At onset 89.7% patients had focal neurological signs and 62.1% had headache. Median CD4 count was 60 (95% CI for median 27-95) lf/cmm. 28 patients had positive T. gondii IgG antibodies in plasma and/or cerebrospinal fluid. Only 6 patients had treatment with cotrimoxazole, most of them being treated with pyrimethamine/sulphadoxine combination and alternatively with atovaquone. 69% of patients had any adverse reactions to Toxo treatment. Most adverse reactions were cutaneous in 10 patients (5 severe) and anemia in 7 patients. Nine patients had antiretroviral therapy (ART) before Toxo diagnosis, out of them 1 had mono, 1 dual therapy, 6 were failing cART and one patient had immune reconstitution syndrome. Ten patients (34.5%) died. The median survival time was 117 months. In univariate analysis survival was correlated with shorter time from onset to admission (p=0.04) while on multivariate analysis diagnosis in the post-cART period was the only factor associated with longer survival (p=0.03). 14 of 19 patients recovered with sequels, most of them motor deficits. Cerebral toxoplasmosis in this particular pediatric cohort shared common features with that reported in adults pertaining to prevalence in pre-cART period and pathogenic mechanism. Survival was associated with a more rapid diagnosis of cerebral toxoplasmosis and with access to cART.

HIV and Aging: Effects on the Central Nervous System

With the introduction of combination antiretroviral therapy, many human immunodeficiency virus-positive (HIV+) individuals are reaching advanced age. The proportion of people living with HIV older than 50 years already exceeds 50% in many communities, and is expected to reach this level nationally by 2015. HIV and aging are independently associated with neuropathological changes, but their concurrence may have a more deleterious effect on the central nervous system (CNS). Published data about neurocognitive and neuroimaging markers of HIV and aging are reviewed. Putative factors contributing to neurocognitive impairment and neuroimaging changes in the aging HIV+ brain, such as metabolic disturbances, cardiovascular risk factors, immune senescence, and neuroinflammation, are described. The possible relationship between HIV and some markers of Alzheimer's disease is presented. Current research findings emphasize multiple mechanisms related to HIV and combination antiretroviral therapy that compromise CNS structure and function with advancing age.

Elevated Risk for Invasive Meningococcal Disease Among Persons With HIV

An association between HIV and invasive meningococcal disease (IMD) has been suggested by several previous studies but has not been fully described in the era of highly active antiretroviral therapy in the United States. To estimate the risk for IMD and death in people living with HIV/AIDS (PLWHA) in New York City (NYC) and the contribution of CD4(+) cell count and viral load (VL) to IMD risk. Comparison of the incidence rate of IMD among PLWHA with that among HIV-uninfected persons. Surveillance data on IMD for patients aged 15 to 64 years from 2000 to 2011 were matched to death and HIV registries to calculate IMD risk and case-fatality ratios. A subset of PLWHA who had a CD4(+) cell count and VL measurement near the time of their IMD infection was included in age-matched case-control analyses to assess HIV markers and IMD risk. Retrospective cohort from communicable disease surveillance. 265 persons aged 15 to 64 years with IMD during 2000 to 2011. Meningococcal and HIV data abstracted from surveillance and registry databases, including CD4(+) cell counts and VL. The average annual incidence rate of IMD was 0.39 cases per 100 000 persons. The relative risk for IMD among PLWHA in NYC during 2000 to 2011 was 10.0 (95% CI, 7.2 to 14.1). Among PLWHA, patients with IMD were 5.3 times (CI, 1.4 to 20.4 times) as likely as age-matched control patients to have CD4(+) counts less than 0.200 × 10(9) cells/L. Missing data on smoking status and comorbidity. People living with HIV/AIDS in NYC are at increased risk for IMD. Cost-effectiveness and vaccine efficacy studies are needed to evaluate the value of a national recommendation for routine meningococcal vaccination of PLWHA. New York City Tax Levy.

Seroprevalence of HBV, HCV, HIV and Syphilis Markers among Blood Donors at Suez Canal University Hospital Blood Bank

Background; The aim of this study was to determine the seroprevalence of Hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (anti-HCV), anti-human immunodeficiency virus (anti-HIV), and VDRL in blood donors in Suez Canal University hospital, blood bank in Ismailia. Methods: This was a retrospective, descriptive study. All blood donors’ records from January 1996 to December 2011 were included; we analyzed data from 149,381 blood samples collected. Data were evaluated with SPSS and differences in prevalence, gender, and residence were calculated using the x2 test. Results: The seroprevalence of HBsAg and anti-HCV were 2.3% (3440) and 7.2% (10729), respectively. The annual Anti-HCV prevalence dropped significantly (P 0.05). Both HBsAg and anti-HCV showed higher prevalence among male (2.3%, 7.3%, respectively) and rural donors (2.6%, 7.9%, respectively) more than female (2.1%, 6.6%, respectively) and urban donors (2%, 6.6%, respectively). We did not have any positive HIV or syphilis cases in our study. Conclusion: It is of utmost importance to continue screening donated blood with highly sensitive and specific tests to ensure the safety of blood for recipient.