Elena Alvarez

Hospital Carlos III - Madrid, Madrid, Madrid, Spain

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Publications (8)42.56 Total impact

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    ABSTRACT: Raltegravir (RAL) resistance is associated with the selection of integrase mutations at positions 92, 143, 148, and/or 155. A substantial proportion of RAL failures, however, occurs in the absence of these changes. An examination of RAL plasma concentrations may help in interpreting this observation. All early RAL virological failures seen at 22 clinics in Spain during 2009 were identified. HIV integrase sequences and RAL plasma trough concentrations (C(t)) were examined. A total of 106 patients experiencing virological failure on RAL were identified. Only the earliest sample on failure was examined. Integrase sequences could be obtained for 89 (84%), of whom 30 (33.7%) depicted primary RAL resistance mutations (15 N155H, eight Q148H/R, three Y143R, one E92Q, and three more than one of them). Another nine (10.1%) patients showed only secondary changes. The remaining 50 RAL early failures (56.2%) did not select any integrase change. RAL C(t) could be measured in 66 patients at failure and in 21 of them before failure. In a control group of 37 patients with viral suppression on RAL, detectable plasma levels were seen in all cases, with greater median RAL C(t) than in failures, either at the time of viral rebound (p<0.001) or before it (p=0.055). Moreover, median C(t) at the time of failure was greater in patients selecting primary RAL resistance mutations than in the rest of the failures (p<0.001). Undetectable RAL C(t) was seen only in patients failing RAL without integrase resistance mutations (64.1% of them). RAL failures in the absence of integrase resistance mutations mainly reflect poor drug compliance.
    AIDS research and human retroviruses 04/2011; 28(2):156-64. DOI:10.1089/AID.2010.0370 · 2.33 Impact Factor
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    ABSTRACT: INTRODUCTION: Knowledge of drug interactions is vital to maximize antiretroviral efficacy and avoid drug-related toxicities. Treatment of co-morbidities has become a difficult task in HIV-infected individuals because pharmacokinetic and/or pharmacodynamic interactions are common when other medications are prescribed along with antiretroviral agents. AREAS COVERED: This article provides an update of the most relevant drug interactions that occur between antiretroviral agents and other drugs. The article additionally revisits how these drug interactions can be prevented from occurring as well as how they can be managed. EXPERT OPINION: Interactions between antiretrovirals and other drugs are frequent in clinical practice. The most common are those affecting drug metabolism due to induction or inhibition of the CYP450, leading to abnormal drug exposure. It is by this mechanism that most HIV protease inhibitors, non-nucleoside reverse transcriptase inhibitors and maraviroc often interact with other medications. In contrast, nucleoside reverse transcriptase inhibitors and some integrase inhibitors, which do not or only marginally affect CYP450, are relatively free of significant pharmacokinetic interactions, although nucleoside analogs might be involved in some pharmacodynamic interactions.
    Expert Opinion on Drug Metabolism &amp Toxicology 02/2011; 7(4):457-77. DOI:10.1517/17425255.2011.558839 · 2.83 Impact Factor
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    ABSTRACT: Given that atazanavir (ATV) increases bilirubin in an exposure-dependent manner, we tested whether bilirubin levels could be used as a surrogate of virological response to ATV-based regimens in 182 patients. Bilirubin increases of ≥0.7 mg/dl were independently associated with early virological response with an odds ratio of 5.2 (95% confidence interval 2.2-11.9). Total bilirubin, a nonexpensive, simple, and widely available parameter, might be used as a surrogate of virological response to ATV-based regimens, especially in areas with limited resources where HIV-RNA testing is not available.
    AIDS research and human retroviruses 02/2011; 27(10):1043-5. DOI:10.1089/AID.2011.0019 · 2.33 Impact Factor
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    Retrovirology 05/2010; 7(Suppl 1). DOI:10.1186/1742-4690-7-S1-P76 · 4.19 Impact Factor
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    ABSTRACT: Tenofovir (TFV) is a nucleotide analogue widely used for the treatment of HIV infection. Despite its proven efficacy and safety, cases of kidney tubular dysfunction have increasingly been reported and concern exists about the risk of nephrotoxicity associated with the long-term use of TFV. Evidences about the renal toxicity associated with TFV use as well as predictors are examined. The most relevant publications assessing TFV safety and those which have reported cases of tubular dysfunction were identified and carefully revised. Renal damage of clinical significance caused by TFV is uncommon in the short-mid-term. It occurs more frequently in subjects with underlying kidney conditions. TFV primarily results in kidney tubular dysfunction and less frequently in glomerular abnormalities. Kidney damage may progress over time under long-term TFV exposure but is reversible in most cases on drug discontinuation. Severe renal damage associated with TFV use is uncommon and of multifactorial origin. However, mild tubular dysfunction is recognized in a substantial proportion of TFV-treated individuals and tends to increase with cumulative exposure.
    Expert Opinion on Drug Safety 04/2010; 9(4):545-59. DOI:10.1517/14740331003627458 · 2.91 Impact Factor
  • Journal of Hepatology 04/2010; 52. DOI:10.1016/S0168-8278(10)61161-0 · 11.34 Impact Factor
  • Journal of Hepatology 04/2010; 52. DOI:10.1016/S0168-8278(10)60284-X · 11.34 Impact Factor
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    ABSTRACT: Patients with chronic hepatitis C virus (HCV) infection experience antiretroviral-associated liver toxicity more frequently than HIV mono-infected persons. Herein, we report the hepatic safety profile of raltegravir in a relatively large group of HIV/HCV co-infected patients, a population that was poorly represented in the registrational studies. Prospective, observational study of all antiretroviral-experienced HIV-infected patients who initiated raltegravir from January 2006 to January 2009 at a reference HIV clinic. Clinical data, laboratory parameters and liver stiffness measured at baseline, week 4 and every 3 months thereafter were collected. Chronic hepatitis C was defined as positive serum HCV-RNA. Grade 1-4 hepatotoxicity was defined following the AIDS Clinical Trials Group definition for liver enzyme elevations (LEEs). A control group of patients who initiated protease inhibitors (PIs) or non-nucleoside reverse transcriptase inhibitors (NNRTIs) was examined similarly. Data from 218 HIV-infected patients on raltegravir were analysed, 126 HIV mono-infected and 92 HIV/HCV co-infected patients. Any degree of LEEs occurred in 10 (7.9%) HIV mono-infected and 23 (25%) co-infected patients (relative risk 3.1; 95% confidence interval 2.9-3.4; P = 0.002). Severe hepatotoxicity (grade 3-4), however, was only seen in 3 (1.4%) patients, all co-infected with HCV. It occurred at months 1, 15 and 15, respectively. In all three subjects other reasons than raltegravir exposure most likely explained LEEs. Multivariate analysis revealed HCV co-infection as the only independent variable associated with any degree of hepatotoxicity on raltegravir (P = 0.03). Finally, the rate of LEEs in patients on raltegravir was lower than in those who were treated with PIs or NNRTIs. LEEs are less frequent in patients treated with raltegravir than with other antiretroviral drug classes. However, HIV/HCV co-infected patients treated with raltegravir experienced LEEs more frequently than HIV mono-infected persons. In this series, LEEs in patients treated with raltegravir were uniformly mild and no cases of grade 3-4 hepatotoxicity could be directly attributed to the drug. These results reinforce the overall hepatic safety profile of raltegravir.
    Journal of Antimicrobial Chemotherapy 03/2010; 65(3):543-7. DOI:10.1093/jac/dkp446 · 5.31 Impact Factor