Optimizing management of treatment-naïve and treatment-experienced HIV+ patients: the role of maraviroc

Maraviroc is the first CCR5 antagonist approved for the treatment of HIV-1 infection. It specifically inhibits the replication of R5 viruses by blocking viral entry. HIV-1 tropism can be estimated accurately and predict viral response to maraviroc. Genotypic tools are increasingly replacing phenotypic assays in most places. The favorable pharmacokinetic properties and the good safety profile of maraviroc may support an earlier use of the drug in HIV-1 infection, as well as favor its consideration as part of switch strategies in patients under suppressive antiret-roviral regimens containing less-well-tolerated drugs. Moreover, a particular immune benefit of maraviroc might encourage its use as part of intensification strategies in HIV-infected patients with impaired CD4 gains despite prolonged suppression of HIV replication with antiretroviral therapy. However, the long-term consequences of using maraviroc must be carefully checked, given its particular mechanism of action, blocking a physiologic cell receptor

Hyaluronic acid levels predict risk of hepatic encephalopathy and liver-related death in HIV/viral hepatitis coinfected patients

Background: Whereas it is well established that various soluble biomarkers can predict level of liver fibrosis, their ability to predict liver-related clinical outcomes is less clearly established, in particular among HIV/viral hepatitis co-infected persons. We investigated plasma hyaluronic acid’s (HA) ability to predict risk of liver-related events (LRE; hepatic coma or liver-related death) in the EuroSIDA study. Methods: Patients included were positive for anti-HCV and/or HBsAg with at least one available plasma sample. The earliest collected plasma sample was tested for HA (normal range 0–75 ng/mL) and levels were associated with risk of LRE. Change in HA per year of follow-up was estimated after measuring HA levels in latest sample before the LRE for those experiencing this outcome (cases) and in a random selection of one sixth of the remaining patients (controls). Results: During a median of 8.2 years of follow-up, 84/1252 (6.7%) patients developed a LRE. Baseline median (IQR) HA in those without and with a LRE was 31.8 (17.2–62.6) and 221.6 ng/mL (74.9–611.3), respectively (p<0.0001). After adjustment, HA levels predicted risk of contracting a LRE; incidence rate ratios for HA levels 75–250 or ≥250 vs. <75 ng/mL were 5.22 (95% CI 2.86–9.26, p<0.0007) and 28.22 (95% CI 14.95–46.00, p<0.0001), respectively. Median HA levels increased substantially prior to developing a LRE (107.6 ng/mL, IQR 0.8 to 251.1), but remained stable for controls (1.0 ng/mL, IQR –5.1 to 8.2), (p<0.0001 comparing cases and controls), and greater increases predicted risk of a LRE in adjusted models (p<0.001). Conclusions: An elevated level of plasma HA, particularly if the level further increases over time, substantially increases the risk of contracting LRE over the next five years. HA is an inexpensive, standardized and non-invasive supplement to other methods aimed at identifying HIV/viral hepatitis co-infected patients at risk of hepatic complications

The earliest occurrence and remarkable stasis of the family Bostrichidae (Coleoptera: Polyphaga)in Cretaceous Charentes amber.

A new fossil species of auger beetle (Coleoptera: Bostrichidae), preserved in mid-Cretaceous (Albian-Cenomanian) amber from south-western France, is described as Stephanopachys vetus Peris, Delclòs et Perrichot sp. n. The species is the earliest fossil bostrichid discovered to date, but is remarkably similar to Recent species of the genus Stephanopachys, supporting long morphological conservation in wood boring beetles. The specimen is fossilized in fully opaque amber and was imaged in 3D using propagation phase-contrast X-ray synchrotron microtomography. Based on the ecology of extant related species habits, it is suggested that S. vetus sp. n. was a primary succession pioneer following wildfires in mid-Cretaceous forests. The fossil record of the family is reviewed

HIV-1 Infection in Persistently HIV-1-Seronegative Individuals: More Reasons for HIV RNA Screening

Producción CientíficaThe World Health Organization (WHO) has recently released updated guidelines for HIV diagnosis that recommend serum antibody testing by either EIAs or rapid tests and that encourage the identification of unrecognized HIV infections [1]. However, this approach may fail to identify subjects with acute infection. In consideration of the potential public health benefits of not missing individuals in the most contagious phase of infection, implementation of routine HIV RNA screening has been suggested [2]. We want to stress that there are other situations in which viral load is detectable in the absence of reactive antibody tests and in which the introduction of nucleic acid testing may be beneficial. This is the case for HIV-infected subjects in whom specific antibody responses are absent, as for the case reported here.Fondo de Investigaciones Sanitarias (project CP05/00300)Fundación para la Investigación y Prevención del Sida en España (project 36483/05)Fundación Investigación y Educación en Sida.RIS (project ISCIII-RETIC RD06

Unexplained severe portal hypertension in HIV-infected patients: a new clinical entity?

Cases of non-cirrhotic portal hypertension have been reported in HIV-negative patients as a result from exposure to adenosine analogues (e.g. azathioprine), bacterial infections, trace metals and chemicals, genetic coagulation disorders and/or autoimmune diseases. More recently, reports of similar cases in HIV-positive individuals have attracted much attention

New, primitive termites (Isoptera) from Early Cretaceous ambers of France and Lebanon

This is the publisher's version, also available electronically from palaeodiversity.org.Three new genera and species of primitive termites (Isoptera) are described and figured from Early Cretaceous French and Lebanese ambers: Santonitermes chloeae ENGEL, NEL & PERRICHOT, n. gen., n. sp., from an imago preserved in Charentese amber (Albian–Cenomanian); Syagriotermes salomeae ENGEL, NEL & PERRICHOT, n. gen., n. sp., from an alate detected in opaque amber from the same locality and reconstructed using synchrotron microtomographic imaging; and Lebanotermes veltzae ENGEL, AZAR & NEL, n. gen., n. sp., from an alate preserved in Lebanese amber (Aptian). The three genera exhibit primitive features of the Meiatermes-grade of early isopteran genera (sensu ENGEL et al. 2009). In addition, three further fragmentary specimens from Lebanon amber are reported, each apparently distinct from Lebanotermes n. gen. and the previously described Melqartitermes ENGEL et al., 2007. The new fossils further document the diversity and morphological disparity of ‘lower’ termite groups during the Early Cretaceous, highlighting the importance of palaeontological material for understanding isopteran phylogeny as well as the diversification of Isoptera in the latest Jurassic and Early Cretaceous

Influence of Hepatitis C Virus Infection on HIV-1 Disease Progression and Response to Highly Active Antiretroviral Therapy

ObjectiveTo assess hepatitis C virus (HCV) antibody prevalence in the EuroSIDA cohort, along with survival, human immunodeficiency virus (HIV)-1 disease progression, virologic response (plasma HIV-1 RNA load of <500 copies/mL), and CD4 cell count recovery by HCV serostatus in patients initiating highly active antiretroviral therapy (HAART) ResultsHCV serostatus at or before enrollment was available for 5957 patients; 1960 (33%) and 3997 (67%) were HCV seropositive and seronegative, respectively. No association between an increased incidence of acquired immunodeficiency syndrome-defining illnesses or death and HCV serostatus was seen after adjustment for other prognostic risk factors known at baseline (adjusted incidence rate ratio [IRR], 0.97 [95% confidence interval {CI}, 0.81-1.16]). However, there was a large increase in the incidence of liver disease-related deaths in HCV-seropositive patients in adjusted models (IRR, 11.71 [95% CI, 6.42-21.34]). Among 2260 patients of known HCV serostatus initiating HAART, after adjustment, there was no significant difference between HCV-seropositive and -seronegative patients with respect to virologic response (relative hazard [RH], 1.13 [95% CI, 0.84-1.51]) and immunologic response, whether measured as a ⩾50% increase (RH, 0.94 [95% CI, 0.77-1.16]) or a ⩾50 cells/μL increase (RH, 0.92 [95% CI, 0.77-1.11]) in CD4 cell count after HAART initiation ConclusionsHCV serostatus did not affect the risk of HIV-1 disease progression, but the risk of liver disease-related deaths was markedly increased in HCV-seropositive patients. The overall virologic and immunologic responses to HAART were not affected by HCV serostatu

Development of Tropical Spastic Paraparesis in Human T-Lymphotropic Virus Type 1 Carriers Is Influenced by Interleukin 28B Gene Polymorphisms

Producción CientíficaInterleukin 28B (IL28B) rs12979860 polymorphisms were examined in 41 individuals with human T-lymphotrophic virus type 1 (HTLV-1). The alleles CT/TT were more frequent in 12 individuals with HTLV-1-associated myelopathy/tropical spastic paraparesis than in 29 asymptomatic carriers (80% vs 20%; P = .03), and median HTLV-1 proviral load was greater in CT/TT than CC carriers (P = .01). Thus, IL28B testing and closer follow-up of HTLV-1 asymptomatic CT/TT carriers is warranted.Fundación Investigación y Educación en Sida Grant (IES) FIS (CP05/00300)Red de Investigación en SIDA Grant (RIS, ISCIII-RETIC RD06/006)Proyecto europeo NEAT Grant (LSHP-CT-2006-037570