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Badalona, Spain

Vandekerckhove L.P.R.,Ghent University | Wensing A.M.J.,University Utrecht | Kaiser R.,University of Cologne | Brun-Vezinet F.,Bichat Claude Bernard University Hospital | And 18 more authors.
The Lancet Infectious Diseases | Year: 2011

Viral tropism is the ability of viruses to enter and infect specific host cells and is based on the ability of viruses to bind to receptors on those cells. Testing for HIV tropism is recommended before prescribing a chemokine receptor blocker. In most European countries, HIV tropism is identified with tropism phenotype testing. New data support genotype analysis of the HIV third hypervariable loop (V3) for the identification of tropism. The European Consensus Group on clinical management of tropism testing was established to make recommendations to clinicians and clinical virologists. The panel recommends HIV-tropism testing for the following groups: drug-naive patients in whom toxic effects are anticipated or for whom few treatment options are available; patients who have poor tolerability to or toxic effects from current treatment or who have CNS pathology; and patients for whom therapy has failed and a change in treatment is considered. In general, an enhanced sensitivity Trofile assay and V3 population genotyping are the recommended methods. Genotypic methods are anticipated to be used more frequently in the clinical setting because of their greater accessibility, lower cost, and faster turnaround time than other methods. For the interpretation of V3 loop genotyping, clinically validated systems should be used when possible. Laboratories doing HIV tropism tests should have adequate quality assurance measures. Similarly, close collaboration between HIV clinicians and virologists is needed to ensure adequate diagnostic and treatment decisions. © 2011 Elsevier Ltd. Source


Llibre J.M.,Foundation University | Llibre J.M.,Autonomous University of Barcelona | Clotet B.,Irsicaixa Foundation
AIDS Reviews | Year: 2012

Once-daily single-tablet regimens represent the paramount simplification of antiretroviral treatment achieved so far. They include drugs with favorable pharmacokinetics that allow once-daily administration, that do not need dose adjustments, have no additional toxicities, and do not require dissimilar intake conditions. Co-formulated efavirenz/tenofovir disoproxil fumarate/emtricitabine has been a gold standard of initial therapy since its approval in 2006. Galenic research and industry patent agreements may allow availability of single-tablet regimens with HIV-1 nonnucleoside reverse transcriptase inhibitors (efavirenz or rilpivirine), integrase inhibitors (cobicistat-boosted elvitegravir or dolutegravir), and protease inhibitors (cobicistat-boosted darunavir), combined with either tenofovir disoproxil fumarate/emtricitabine or abacavir/lamivudine. The introduction of the new phamacoenhancer cobicistat as a potential substitution for ritonavir and the investigational agent GS-7340, with one-tenth the tenofovir mass, is a breakthrough in antiretroviral drug development. Many HIV-1-infected patients who are treatment-naive or treatment-experienced with susceptible virus will potentially have more options to reduce pill burden and optimize dosage schedules with one pill once-daily regimens. Source


Demetriou V.L.,University of Cyprus | van de Vijver D.A.M.C.,Erasmus Medical Center | Kousiappa I.,University of Cyprus | Balotta C.,University of Milan | And 15 more authors.
PLoS ONE | Year: 2010

Background HIV-1 genotypic drug resistance is an important threat to the success of antiretroviral therapy and transmitted resistance has reached 9% prevalence in Europe. Studies have demonstrated that HIV-1 DNA load in peripheral blood mononuclear cells (PBMC) have a predictive value for disease progression, independently of CD4 counts and plasma viral load. Methodology/Principal Findings Molecular-beacon-based real-time PCR was used to measure HIV-1 second template switch (STS) DNA in PBMC in newly-diagnosed HIV-1 patients across Europe. These patients were representative for the HIV-1 epidemic in the participating countries and were carrying either drug-resistant or sensitive viral strains. The assay design was improved from a previous version to specifically detect M-group HIV-1 and human CCR5 alleles. The findings resulted in a median of 3.32 log10 HIV-1 copies/106 PBMC and demonstrated for the first time no correlation between cellular HIV-1 DNA load and transmitted drug-resistance. A weak association between cellular HIV-1 DNA levels with plasma viral RNA load and CD4+ T-cell counts was also reconfirmed. Co-receptor tropism for 91% of samples, whether or not they conferred resistance, was CCR5. A comparison of pol sequences derived from RNA and DNA, resulted in a high similarity between the two. Conclusions/Significance An improved molecular-beacon-based real-time PCR assay is reported for the measurement of HIV-1 DNA in PBMC and has investigated the association between cellular HIV-1 DNA levels and transmitted resistance to antiretroviral therapy in newly-diagnosed patients from across Europe. The findings show no correlation between these two parameters, suggesting that transmitted resistance does not impact disease progression in HIV-1 infected individuals. The CCR5 co-receptor tropism predominance implies that both resistant and non-resistant strains behave similarly in early infection. Furthermore, a correlation found between RNA- and DNA-derived sequences in the pol region suggests that genotypic drug-resistance testing could be carried out on either template. © 2010 Demetriou et al. Source


Pineda-Pena A.-C.,Rega Institute for Medical Research | Pineda-Pena A.-C.,El Rosario University | Schrooten Y.,Rega Institute for Medical Research | Schrooten Y.,University Hospitals Leuven | And 30 more authors.
PLoS ONE | Year: 2014

We aimed to study epidemic trends and predictors for transmitted drug resistance (TDR) in our region, its clinical impact and its association with transmission clusters. We included 778 patients from the AIDS Reference Center in Leuven (Belgium) diagnosed from 1998 to 2012. Resistance testing was performed using population-based sequencing and TDR was estimated using the WHO-2009 surveillance list. Phylogenetic analysis was performed using maximum likelihood and Bayesian techniques. The cohort was predominantly Belgian (58.4%), men who have sex with men (MSM) (42.8%), and chronically infected (86.5%). The overall TDR prevalence was 9.6% (95% confidence interval (CI): 7.7-11.9), 6.5% (CI: 5.0-8.5) for nucleoside reverse transcriptase inhibitors (NRTI), 2.2% (CI: 1.4-3.5) for non-NRTI (NNRTI), and 2.2% (CI: 1.4-3.5) for protease inhibitors. A significant parabolic trend of NNRTI-TDR was found (p = 0.019). Factors significantly associated with TDR in univariate analysis were male gender, Belgian origin, MSM, recent infection, transmission clusters and subtype B, while multivariate and Bayesian network analysis singled out subtype B as the most predictive factor of TDR. Subtype B was related with transmission clusters with TDR that included 42.6% of the TDR patients. Thanks to resistance testing, 83% of the patients with TDR who started therapy had undetectable viral load whereas half of the patients would likely have received a suboptimal therapy without this test. In conclusion, TDR remained stable and a NNRTI up-and-down trend was observed. While the presence of clusters with TDR is worrying, we could not identify an independent, non-sequence based predictor for TDR or transmission clusters with TDR that could help with guidelines or public health measures. © 2014 Pineda-Peña et al. Source


Luo R.,University of Delaware | Cardozo E.F.,University of Delaware | Piovoso M.J.,Pennsylvania State University | Wu H.,University of Rochester | And 5 more authors.
Journal of the Royal Society Interface | Year: 2013

A model of reservoir activation and viral replication is introduced accounting for the production of 2-LTR HIV-1 DNA circles following antiviral intensification with the HIV integrase inhibitor raltegravir, considering contributions of de novo infection events and exogenous sources of infected cells, including quiescent infected cell activation. The model shows that a monotonic increase in measured 2-LTR concentration post intensification is consistent with limited de novo infection primarily maintained by sources of infected cells unaffected by raltegravir, such as quiescent cell activation, while a transient increase in measured 2-LTR concentration is consistent with significant levels of efficient (R0 > 1) de novo infection. The model is validated against patient data from the INTEGRAL study and is shown to have a statistically significant fit relative to the null hypothesis of random measurement variation about a mean. We obtain estimates and confidence intervals for the model parameters, including 2-LTR half-life. Seven of the 13 patients with detectable 2-LTR concentrations from the INTEGRAL study have measured 2-LTR dynamics consistent with significant levels of efficient replication of the virus prior to treatment intensification. © 2013 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License. Source

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