Correlations between atazanavir Ctrough and hyperbilirubinemia: a case report

<p>Abstract</p> <p>Introduction</p> <p>Hyperbilirubinemia is a common side effect of the antiretroviral agent atazanavir but is generally reversible upon discontinuation of treatment. We used therapeutic drug monitoring to investigate the occurrence of hyperbilirubinemia in a 49-year-old Hispanic man infected with HIV, following an overdose of ritonavir in ritonavir-boosted atazanavir therapy.</p> <p>Case presentation</p> <p>A 49-year-old Hispanic man with HIV who had received several highly active antiretroviral therapy regimens over a number of years including atazanavir-containing regimens, was diagnosed with hyperbilirubinemia. An inappropriate doubling of ritonavir boosting resulted in a high atazanavir C_troughand an initial rise in bilirubin plasma levels. Bilirubin levels later decreased, probably as a consequence of enzyme induction, while atazanavir plasma concentrations remained elevated.</p> <p>Conclusion</p> <p>This article describes an occurrence of hyperbilirubinemia in a man infected with HIV and supports the importance of therapeutic drug monitoring in investigations of hyperbilirubinemia among patients receiving antiretroviral agents. That the patient tolerated exceptionally high atazanavir levels further strengthens the tolerability profile of this drug.</p

HIFI spectroscopy of low-level water transitions in M82

We present observations of the rotational ortho-water ground transition, the two lowest para-water transitions, and the ground transition of ionised ortho-water in the archetypal starburst galaxy M82, performed with the HIFI instrument on the Herschel Space Observatory. These observations are the first detections of the para-H2O(111-000) (1113\,GHz) and ortho-H2O+(111-000) (1115\,GHz) lines in an extragalactic source. All three water lines show different spectral line profiles, underlining the need for high spectral resolution in interpreting line formation processes. Using the line shape of the para-H2O(111-000) and ortho-H2O+(111-000) absorption profile in conjunction with high spatial resolution CO observations, we show that the (ionised) water absorption arises from a ~2000 pc^2 region within the HIFI beam located about ~50 pc east of the dynamical centre of the galaxy. This region does not coincide with any of the known line emission peaks that have been identified in other molecular tracers, with the exception of HCO. Our data suggest that water and ionised water within this region have high (up to 75%) area-covering factors of the underlying continuum. This indicates that water is not associated with small, dense cores within the ISM of M82 but arises from a more widespread diffuse gas component.Comment: 5 pages, 4 figures. Accepted for publication in A&

Comparative evaluation of seven resistance interpretation algorithms and their derived genotypic inhibitory quotients for the prediction of 48 week virological response to darunavir-based salvage regimens

Background: the darunavir genotypic inhibitory quotient (gIQ) has been suggested as one of the predictors of virological response to darunavir-containing salvage regimens. Nevertheless, which resistance algorithm should be used to optimize the calculation of gIQ is still debated. The aim of our study was to compare seven different free-access resistance algorithms and their derived gIQs as predictors of 48 week virological response to darunavir-based salvage therapy in the clinical setting. Methods: patients placed on two nucleoside reverse transcriptase inhibitors\u200a+\u200a600/100 mg of darunavir/ritonavir twice daily \u200a\ub1\u200a enfuvirtide were prospectively evaluated. Virological response was assessed at 48 weeks. Darunavir resistance interpretation was performed according to seven different algorithms, of which two were weighted algorithms. Analysis of other factors potentially associated with virological response at 48 weeks was performed. Results: fifty-six treatment-experienced patients were included. Overall, 35 patients (62.5%) had a virological response at 48 weeks. Receiver operator characteristic curve analysis showed that De Meyer's weighted score (WS) and its derived gIQ (gIQ WS) were the most accurate parameters defining virological response, and related cut-offs showed the best sensitivity/specificity pattern. In univariate logistic regression analysis, baseline log viral load (P = 0.028), optimized background score 65 2 (P = 0.048), WS >5 (P = 0.001) and WS gIQ 65 600 (P\u200a<\u200a0.0001) were independently associated with virological response. In multivariate analysis, only baseline log viral load (P = 0.008) and WS gIQ 65 600 (P < 0.0001) remained in the model. Conclusions: in our study, although different resistance interpretation algorithms and derived gIQs were associated with virological response, gIQ WS was the most accurate predictive model for achieving a successful virological response

HTLV-1 infection in solid organ transplant donors and recipients in Spain

Background: HTLV-1 infection is a neglected disease, despite infecting 10–15 million people worldwide and severe illnesses develop in 10% of carriers lifelong. Acknowledging a greater risk for developing HTLV-1 associated illnesses due to immunosuppression, screening is being widely considered in the transplantation setting. Herein, we report the experience with universal HTLV testing of donors and recipients of solid organ transplants in a survey conducted in Spain. Methods: All hospitals belonging to the Spanish HTLV network were invited to participate in the study. Briefly, HTLV antibody screening was performed retrospectively in all specimens collected from solid organ donors and recipients attended since the year 2008. Results: A total of 5751 individuals were tested for HTLV antibodies at 8 sites. Donors represented 2312 (42.2%), of whom 17 (0.3%) were living kidney donors. The remaining 3439 (59.8%) were recipients. Spaniards represented nearly 80%. Overall, 9 individuals (0.16%) were initially reactive for HTLV antibodies. Six were donors and 3 were recipients. Using confirmatory tests, HTLV-1 could be confirmed in only two donors, one Spaniard and another from Colombia. Both kidneys of the Spaniard were inadvertently transplanted. Subacute myelopathy developed within 1 year in one recipient. The second recipient seroconverted for HTLV-1 but the kidney had to be removed soon due to rejection. Immunosuppression was stopped and 3 years later the patient remains in dialysis but otherwise asymptomatic. Conclusion: The rate of HTLV-1 is low but not negligible in donors/recipients of solid organ transplants in Spain. Universal HTLV screening should be recommended in all donor and recipients of solid organ transplantation in Spain. Evidence is overwhelming for very high virus transmission and increased risk along with the rapid development of subacute myelopath

Rapid subacute myelopathy following kidney transplantation from HTLV-1 donors: role of immunosuppresors and failure of antiretrovirals

Two kidney transplant recipients from a single donor became infected with HTLV-1 (human T-lymphotropic virus type 1) in Spain. One developed myelopathy 8 months following surgery despite early prescription of antiretroviral therapy. The allograft was removed from the second recipient at month 8 due to rejection and immunosuppressors discontinued. To date, 3 years later, this patient remains infected but asymptomatic. HTLV-1 infection was recognized retrospectively in the donor, a native Spaniard who had sex partners from endemic regions. Our findings call for a reappraisal of screening policies on donor-recipient organ transplantation. Based on the high risk of disease development and the large flux of persons from HTLV-1 endemic regions, pre-transplant HTLV-1 testing should be mandatory in Spain

ELISA versus PCR for diagnosis of chronic Chagas disease: systematic review and meta-analysis

<p>Abstract</p> <p>Background</p> <p>Most current guidelines recommend two serological tests to diagnose chronic Chagas disease. When serological tests are persistently inconclusive, some guidelines recommend molecular tests. The aim of this investigation was to review chronic Chagas disease diagnosis literature and to summarize results of ELISA and PCR performance.</p> <p>Methods</p> <p>A systematic review was conducted searching remote databases (MEDLINE, LILACS, EMBASE, SCOPUS and ISIWeb) and full texts bibliography for relevant abstracts. In addition, manufacturers of commercial tests were contacted. Original investigations were eligible if they estimated sensitivity and specificity, or reliability -or if their calculation was possible - of ELISA or PCR tests, for chronic Chagas disease.</p> <p>Results</p> <p>Heterogeneity was high within each test (ELISA and PCR) and threshold effect was detected only in a particular subgroup. Reference standard blinding partially explained heterogeneity in ELISA studies, and pooled sensitivity and specificity were 97.7% [96.7%-98.5%] and 96.3% [94.6%-97.6%] respectively. Commercial ELISA with recombinant antigens studied in phase three investigations partially explained heterogeneity, and pooled sensitivity and specificity were 99.3% [97.9%-99.9%] and 97.5% [88.5%-99.5%] respectively. ELISA's reliability was seldom studied but was considered acceptable. PCR heterogeneity was not explained, but a threshold effect was detected in three groups created by using guanidine and boiling the sample before DNA extraction. PCR sensitivity is likely to be between 50% and 90%, while its specificity is close to 100%. PCR reliability was never studied.</p> <p>Conclusions</p> <p>Both conventional and recombinant based ELISA give useful information, however there are commercial tests without technical reports and therefore were not included in this review. Physicians need to have access to technical reports to understand if these serological tests are similar to those included in this review and therefore correctly order and interpret test results. Currently, PCR should not be used in clinical practice for chronic Chagas disease diagnosis and there is no PCR test commercially available for this purpose. Tests limitations and directions for future research are discussed.</p

HIV interactions with monocytes and dendritic cells: viral latency and reservoirs

HIV is a devastating human pathogen that causes serious immunological diseases in humans around the world. The virus is able to remain latent in an infected host for many years, allowing for the long-term survival of the virus and inevitably prolonging the infection process. The location and mechanisms of HIV latency are under investigation and remain important topics in the study of viral pathogenesis. Given that HIV is a blood-borne pathogen, a number of cell types have been proposed to be the sites of latency, including resting memory CD4+ T cells, peripheral blood monocytes, dendritic cells and macrophages in the lymph nodes, and haematopoietic stem cells in the bone marrow. This review updates the latest advances in the study of HIV interactions with monocytes and dendritic cells, and highlights the potential role of these cells as viral reservoirs and the effects of the HIV-host-cell interactions on viral pathogenesis

Anti-inflammatory Components from Functional Foods for Obesity

Obesity, defined as excessive fat accumulation that may impair health, has been described throughout human history, but it has now reached epidemic proportions with the WHO estimating that 39% of the world’s adults over 18 years of age were overweight or obese in 2016. Obesity is a chronic low-grade inflammatory state leading to organ damage with an increased risk of common diseases including cardiovascular and metabolic disease, non-alcoholic fatty liver disease, osteo-arthritis and some cancers. This inflammatory state may be influenced by adipose tissue hypoxia and changes in the gut microbiota. There has been an increasing focus on functional foods and nutraceuticals as treatment options for obesity as drug treatments are limited in efficacy. This chapter summarises the importance of anthocyanin-containing fruits and vegetables, coffee and its components, tropical fruit and food waste as sources of phytochemicals for obesity treatment. We emphasise that preclinical studies can form the basis for clinical trials to determine the effectiveness of these treatments in humans