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Available from: Alessandra Barassi, Aug 21, 2014
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    ABSTRACT: OBJECTIVE:To systematically examine the literature assessing the effect of uridine 5'-diphospho-glucuronosyltransferase (UGT) 1A1*28 genetic polymorphisms on atazanavir-associated hyperbilirubinemia.DATA SOURCES:MEDLINE (1948-November 2012), EMBASE (1980-November 2012), International Pharmaceutical Abstracts (1970-November 2012), Google, and Google Scholar were searched using combinations of the following terms: glucuronosyltransferase, glucuronosyltransferase 1A1, atazanavir, atazanavir plus ritonavir, or polymorph$. The reference lists of all identified articles were manually searched.STUDY SELECTION AND DATA EXTRACTION:Studies were included if at least 1 group of patients received atazanavir therapy and assessed the effect of UGT1A1*28 variants on bilirubin concentrations or atazanavir discontinuation rates. The quality of each study was ranked according to the US Preventive Services Task Force 1996 clas sification system. Information extracted included study design, baseline characteristics, treatment regimens, UGT1A1*28 genotype frequencies, bilirubin concentrations, incidence of hyperbilirubinemia, and atazanavir discontinuation rates.DATA SYNTHESIS:Our search produced 12 studies, of which 9 were included (6 full manuscripts [level II-2], 2 abstracts, and 1 letter to the editor [level III]). Reported UGT1A1*28 homozygote genotype frequencies (0.8-23.8%) were in general agreement with the literature for the diverse ethnic population captured in the 9 studies. An association between the incidence of hyperbilirubinemia and UGT1A1*28 genotype (homozygotes > heterozygotes > wild-type) was demonstrated in all studies that reported such data (6 of 9 studies). However, the calculated positive predictive value for homozygosity and hyperbilirubinemia from pooled data was low (40.3%). Only 2 studies (levels II-2 and III) reported rates of atazanavir discontinuation due to hyperbilirubinemia and showed some positive correlation with presence of the UGT1A1*28 allele.CONCLUSIONS:Based on the available evidence, homozygosity of the UGT1A1*28 allele does not strongly predict the incidence of severe hyper bilirubinemia. Thus, until large, prospective trials demonstrate otherwise, UGT1A1*28 testing does not appear to provide additional information to aid clinical decision-making when initiating atazanavir treatment in HIV-infected patients.
    Annals of Pharmacotherapy 04/2013; 47(4). DOI:10.1345/aph.1R550 · 2.06 Impact Factor
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    ABSTRACT: Despite increasing numbers of women with HIV worldwide, females are underrepresented in clinical trials of antiretrovirals and literature addressing gender differences in clinical outcomes, treatment discontinuation, adverse events and adherence are limited. Most recommendations specific to women in current guidelines relate to pregnant women or women wishing to become pregnant. This purpose of this review is to provide clinicians with an overview of available literature regarding the use of ritonavir-boosted atazanavir (ATV/r) in women. The online databases PubMed and EMBASE, HIV-related conference abstracts and reference lists of relevant articles were searched according to predefined terms and limited to items published from 01/10/2007 to 01/10/2012. Updates to conference presentations were checked for substantive journal publication up to 28/11/2013. Of the 294 initial citations retrieved, manual selection identified 19 relevant publications describing gender-based analyses of ATV/r. Publications describing gender-based differences in efficacy, safety, tolerability, pharmacokinetics, drug-drug interactions and adherence are critically evaluated. As part of a combination ART regimen, ATV/r appears to be a safe, effective and durable option for treatment-naïve and early treatment-experienced patients with HIV-1 infection, including non-pregnant and pregnant women.
    Antiviral therapy 01/2014; 19(3). DOI:10.3851/IMP2742 · 3.02 Impact Factor
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    ABSTRACT: Introduction: Human genetic testing is rapidly entering into most medical disciplines, mainly as a way to predict hereditary conditions including predisposition to cancers or degenerative diseases. Another area of interest for human genomics is to ascertain the therapeutic effect and prevent potential toxicities and/or drug-drug interactions of medication. Areas covered: Several human genotypes have been associated with differences in the metabolism and transport of antiretroviral agents that ultimately affect drug exposure. The accelerated discovery of new gene mutations and polymorphisms that influence the effects of antiretroviral drugs provides a unique opportunity for a personalized medicine approach in the management of lifelong HIV therapy. Expert opinion: Integration of human genomic screening into HIV clinical management will be cost-effective, maximizing the benefit of drugs with the lowest risk of side effects for a given patient.
    Expert Opinion on Drug Metabolism &amp Toxicology 06/2014; 10(8):1-12. DOI:10.1517/17425255.2014.930128 · 2.83 Impact Factor