Eugenia Quiros Roldan

Liver Damage and Kinetics of Hepatitis C Virus and Human Immunodeficiency Virus Replication during the Early Phases of Combination Antiretroviral Treatment

In order to assess the relationship between human immunodeficiency virus (HIV) RNA, hepatitis C virus (HCV) RNA, CD4, CD8, and liver enzymes during combination antiretroviral therapy, these parameters were measured in 12 HIV-HCV-coinfected patients (who were naive for antiretrovirals) on the day before and 3, 7, 14, 28, 56, and 84 days after initiating the following treatments: stavudine and lamivudine in all patients, indinavir in 6 patients, and nevirapine in 6 patients. HIV RNA declined rapidly, CD4 cells increased slowly, and CD8 cells and liver enzymes were stable. HCV RNA showed a transient significant increase at days 14 and 21 (7.33+/-0.16 [mean +/- SE] and 7.29+/-0.2 log copies/mL vs. 7+/-0.2 log copies/mL at baseline; P<.05). These changes were similar in both treatment groups. A 2-fold alanine aminotransferase increase was observed in 4 of 12 patients; 4 of 4 patients showed increased HCV RNA. The relationship between HCV RNA increase and HIV RNA decrease indicates virus-virus interference. An HCV RNA increase may cause significant liver damage only in a minority of patients.

Different TCRBV genes generate biased patterns of V-D-J diversity in human T cells

The aim of this work was to assess whether each T-cell receptor (TCR) BV segment generates a random pattern of junctional diversity or if, alternatively, biased patterns of V-D-J rearrangements limit the number of available TCR specificities. Detailed molecular analysis of T-cell receptors expressed by lymphocytes was obtained by generating a large number of junctional regions sequences from TCRBV3, TCRBV4, TCRBV5S1, TCRBV12, TCRBV13S2, TCRBV17, TCRBV20, and TCRBV22 variable genes. The > 800 sequences analyzed have allowed the characterization of the recombination frequencies of each germline-encoded V,D, and J segments, as well as of the magnitude of exonucleolytic nibbling and of the number of N nucleotides inserted for each group of TCRB segments. The data obtained indicate that the extent of junctional diversity varies considerably depending on the TCRBV gene implicated in the recombination event, due to the occurrence of skewed patterns of J and D region usage. Furthermore, our results show that “illegitimate” rearrangements occur with unexpectedly high incidence, specifically at the level of TCRBD to TCRBJ joining. These findings provide additional information for a more accurate estimation of the size of the TCRBV repertoire and for understanding the well-established biased pattern of TCRBV expression in humans.

Detection of skewed T-cell receptor V-β gene usage in the peripheral blood of patients with multiple sclerosis

The ex vivo analysis of the T-cell receptor V-beta (TCRBV) gene usage by circulating T lymphocytes in Multiple Sclerosis (MS) patients may contribute to understanding disease pathogenesis. In the present study, TCRBV gene usage was analyzed in freshly collected unstimulated peripheral blood mononuclear cells (PBMC) isolated from 40 MS patients and 20 healthy controls. Nine patients presented abnormal repertoires, with expansion of one or more TCRBV segments. Among these patients, six presented expansion of TCRBV9 chain expression, three also having an expansion of TCRBV1, TCRBV11 and TCRBV22 segments. The most frequently observed TCRBV chain expansion, TCRBV9, was further analyzed and identified as polyclonal. Evaluation of clinical variables showed that median disease duration was shorter in patients with TCRBV gene expression abnormalities. Longitudinal evaluation of five patients with a skewed repertoire showed regression of expanded TCRBV chains expression to normal values. These data indicate that certain MS patients have abnormal TCRBV gene expression. Such abnormalities are caused by polyclonal expansions of T lymphocyte subpopulations that use the same TCRBV gene families, are unstable and preferentially observed early in the course of the disease.

An outbreak of Serratia marcescens bloodstream infections associated with misuse of drug vials in a surgical ward.

We report an outbreak of Serratia marcescens bloodstream infection due to contamination of total parenteral nutrition solution by insulin or poligeline solution when single-use vials were used for multiple doses in a surgical ward. Four patients had severe sepsis, and no patient died. Multidose vials, used either correctly or incorrectly, may be associated with bloodstream infection.

Haemostatic Activation in HIV Infected Patients Treated with Different Antiretroviral Regimens

HIV infected patients treated with highly active antiretroviral therapy (HAART) may be at increased risk of cardiovascular events, particularly if based upon the use of protease inhibitors (PI). We investigated the haemostatic markers of cardiovascular risk in 115 HIV infected subjects, divided into four groups : 1) patients naïve to antiretroviral therapy (Naïve; n=34 patients), or subjects that had been on a stable combination therapy for > or =12 months with either: 2) double reverse transcriptase nucleoside analogue inhibitors therapy (2NRTI; n=26), 3) 2NRTI backbone plus a non-nucleoside analogue reverse transcriptase inhibitor (NNRTI; n=27), and 4) on a PI based regimen (PI; n=28). Forty-four healthy subjects were included as controls. Naïve as well as 2NRTI and NNRTI differed from controls for higher F1+2 (P<.0001) and FVII (P<.007) levels. When comparing PI patients with controls we observed significantly higher levels of Fbg (P=.035), FVII (P<.0001), TM (P<.0089), vWF (P=.009), and F1+2 (P<.0001). The only difference observed among the 4 groups of HIV infected patients was a significantly lower level of F1+2 in PI as compared with NNRTI patients (P=.05) At least one abnormal result was observed in > or = 90.6% of HIV infects groups, vs 43.2% of controls (P<.0001 in all cases). In conclusion, a) HIV infection per se may alter the haemostatic markers of cardiovascular risk, b) minor differences were observed among the different classes of HIV infected patients, namely between NNRTI and PI treated patients.

Elderly Women With Human Immunodeficiency Virus Infection: Is There an Effect of the Virus on Neuropsychological Profile?

Conflict of Interest: This article is based on Lynn Boyars’s doctoral dissertation at Walden University. Author Contributions: Boyars: study concept and design, acquisition of data, analysis, interpretation of data, preparation of manuscript. Sponsor’s Role: This material is the result of work supported by the use of facilities at the Veterans Affairs Illiana Healthcare System, Danville, Illinois. The views expressed herein are those of the author and do not necessarily reflect the views or the official policy of the Department of Veterans Affairs or the U.S. government.

Atazanavir intracellular concentrations remain stable during pregnancy in HIV-infected patients

Background Atazanavir (300 mg) boosted by ritonavir (100 mg) is the preferred third drug in pregnancy. However, there is still discordance on atazanavir dose increase during the third trimester. Objectives To evaluate plasma and intracellular atazanavir and ritonavir concentrations in HIV-infected women during pregnancy and after delivery. Methods This was an observational study. HIV-infected pregnant patients treated with atazanavir/ritonavir plus either tenofovir/emtricitabine or abacavir/lamivudine had been prospectively enrolled after having signed a written informed consent form. Plasma and intracellular atazanavir and ritonavir Ctrough (24 ± 3 h after drug intake) were measured at each visit during the first, second and third trimesters and post-partum using validated HPLC-MS and HPLC-photodiode array methods (with direct evaluation of cellular volume). Data are described as median (IQR) and compared through non-parametric tests. Results Twenty-five patients were enrolled; at baseline, the median age was 32 years (27-35). All patients had plasma HIV RNA <50 copies/mL; the median CD4+ count was 736 cells/mm3 (542-779). Atazanavir plasma concentrations were 441 ng/mL (261-1557), 710 ng/mL (338-1085), 556 ng/mL (334-1022) and 837 ng/mL (608-1757) during the first, second and third trimesters and post-partum, respectively; intracellular concentrations were 743 ng/mL (610-1928), 808 ng/mL (569-1620), 756 ng/mL (384-1074) and 706 ng/mL (467-2688), respectively. Atazanavir intracellular/plasma ratios were 1.32 (0.98-2.77), 1.34 (1.13-1.88), 1.38 (0.61-2.63) and 1.07 (0.56-2.69), respectively. Atazanavir intracellular concentrations and intracellular/plasma ratios showed non-significant changes over time (P > 0.05). Conclusions This is the first demonstration that intracellular atazanavir exposure remains unchanged during pregnancy supporting the standard 300/100 mg atazanavir/ritonavir dosing throughout pregnancy.

Comparison between the gold standard DXA with calcaneal quantitative ultrasound based-strategy (QUS) to detect osteoporosis in an HIV infected cohort

INTRODUCTION Osteoporosis represents one of the most frequent comorbidity among HIV patients. The current standard method for osteoporosis diagnosis is dual-energy X-ray absorptiometry. Calcaneal quantitative ultrasound can provide information about bone quality. The aims of this study are to compare these two methods and to evaluate their ability to screen for vertebral fracture. METHODS This cross-sectional study was conducted in HIV patients attending the Clinic of Infectious and Tropical Diseases of Brescia during 2014 and who underwent lumbar/femoral dual-energy X-ray absorptiometry, vertebral fracture assessment and calcaneal quantitative ultrasound. The assessment of osteoporosis diagnostic accuracy was performed for calcaneal quantitative ultrasound and for vertebral fracture comparing them with dual-energy X-ray absorptiometry. RESULTS We enrolled 73 patients and almost 48% of them had osteoporosis with at least one of the method used. Vertebral fracture were present in 27.4%. Among patients with normal bone measurements, we found vertebral fracture in proportion between 10% and 30%. If we used calcaneal quantitative ultrasound method and/or X-ray as screening, the percentages of possible savable dual-energy X-ray absorptiometry ranged from 12% to 89% and misclassification rates ranged from 0 to 24.6%. A combined strategy, calcaneal quantitative ultrasound and X-Ray, identified 67% of patients with low risk of osteoporosis, but 16.4% of patients were misclassified. CONCLUSIONS We observed that patients with osteoporosis determined by calcaneal quantitative ultrasound and/or dual-energy X-ray absorptiometry have higher probability to undergo vertebral fracture, but neither of them can be used for predicting vertebral fracture. Use of calcaneal quantitative ultrasound for screening is a reasonable alternative of dual-energy X-ray absorptiometry since our study confirm that none strategy is clearly superior, but both screen tools must be always completed with X-ray.

Prognostic role of inflammatory biomarkers in HIV-infected patients with a first diagnosis of Hepatocellular carcinoma (HCC): a single-centre study: ROLDAN et al.

To assess hepatocellular carcinoma (HCC) survival and to investigate the prognostic role of immunonutritional biomarkers, as neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and prognostic nutritional index (PNI), in a cohort of human immunodeficiency virus (HIV)‐infected patients.