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id="jr-fip-matches">no matches yet</button><a id="jr-fip-next" class="wsprkl btn" title="Jump to next match">▶</a></nav></nav></div><div id="jr-epub-interstitial" class="hidden"></div><div id="jr-content"><article data-type="main"><div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><div class="fm-sec"><h1 id="_NBK279895_"><span class="title" itemprop="name">Maraviroc Therapy and <i>CCR5</i> Genotype</span></h1><p class="contribs">Dean L.</p><p class="fm-aai"><a href="#_NBK279895_pubdet_">Publication Details</a></p><p><em>Estimated reading time: 8 minutes</em></p></div></div><div class="jig-ncbiinpagenav body-content whole_rhythm" data-jigconfig="allHeadingLevels: ['h2'],smoothScroll: false" itemprop="text"><div id="maraviroc.Introduction" itemprop="description"><h2 id="_maraviroc_Introduction_">Introduction</h2><p>Maraviroc is a chemokine receptor antagonist that is used in combination with other antiretroviral agents to treat human immunodeficiency virus type 1 (HIV-1) infection. Maraviroc exerts its therapeutic activity by blocking entry of the HIV-1 virus into immune cells—specifically the CD4-expressing T-helper cells, which play a major role in protecting the body from infection—precursor cells, and dendritic cells.</p><p>HIV-1 infection is classified in two major forms according to the co-receptor it employs to gain entry in to the cell, namely the chemokine receptor 5 (CCR5) or the CXC chemokine receptor 4 (CXCR4). These co-receptors are expressed on different types of cells, and HIV tropism refers to the types of cells and tissues in which the virus infects and replicates. A tropism assay is conducted to determine which co-receptor the HIV-1 virus uses, i.e., whether the virus is CCR5-tropic, CXCR4-tropic, dual tropic (i.e., HIV-1 virus that is able to use both receptors), or mixed tropic (i.e., a mixture of HIV-1 viruses, some of which use CCR5 and others that use CXCR4).</p><p>Maraviroc is only indicated for treatment of adults with CCR5 tropic HIV-1 and is not recommended when the CXCR4-tropic virus has been detected. The FDA-approved drug label for maraviroc states that “prior to initiation of maraviroc, test all patients for CCR5 tropism using a highly sensitive tropism assay” (<a class="bibr" href="#maraviroc.REF.1" rid="maraviroc.REF.1">1</a>).</p></div><div id="maraviroc.Drug_Maraviroc"><h2 id="_maraviroc_Drug_Maraviroc_">Drug: Maraviroc</h2><p>Maraviroc is the first FDA-approved drug in a class of HIV drugs called entry and fusion inhibitors. Maraviroc blocks the interaction between HIV-1 and CCR5 in healthy immune cells, preventing certain strains (CCR5-tropic) of HIV from entering and infecting the cell. Maraviroc must be taken twice daily and must always be used with other HIV drugs. Taken in combination with these drugs, maraviroc may lower the HIV virus load in the blood.</p><p>Currently, maraviroc is the only CCR5 co-receptor inhibitor that has been approved for clinical use (<a class="bibr" href="#maraviroc.REF.2" rid="maraviroc.REF.2">2</a>). It is used to treat HIV-1-infected patients who have a virus that uses CCR5 for entry, and either never received antiretroviral treatment before, or have experienced therapeutic failure following traditional antiretroviral therapies (<a class="bibr" href="#maraviroc.REF.3" rid="maraviroc.REF.3">3</a>).</p><p>Maraviroc treatment regimens may be used less often than other regimens. Possible reasons include the requirement to test for tropism, which is time-consuming and expensive (see <a href="#maraviroc.Genetic_Testing">Genetic Testing</a>). Furthermore, there is a large selection of potent and tolerable treatment regimens currently available that do not require genotyping prior to use. These treatment regimens may be based on nucleoside reverse transcriptase inhibitors (NRTI), non-nucleoside reverse-transcriptase inhibitors (NNRTI), boosted protease inhibitors (PI), and integrase inhibitors (<a class="bibr" href="#maraviroc.REF.2" rid="maraviroc.REF.2">2</a>, <a class="bibr" href="#maraviroc.REF.4" rid="maraviroc.REF.4">4</a>).</p><p>The entry of HIV-1 into a host cell is a complex process, which begins when the viral envelope glycoprotein, gp120, binds to the cellular protein, CD4. Binding induces conformational changes in gp120 resulting in the exposure of gp4, another viral envelope protein that helps mediate the interaction between the virus and cellular co-receptors, and the fusion of viral and cellular membranes.</p><p>The CD4 count is often used to determine the stages of HIV disease. CD4 is a glycoprotein found on the surface of T helper immune cells. HIV-1 infection leads to a progressive reduction in the number of T cells that express CD4, and a CD4 count of less than 200 cells/mm<sup>3</sup> is one of the qualifications for a diagnosis of AIDS (<a class="bibr" href="#maraviroc.REF.5" rid="maraviroc.REF.5">5</a>, <a class="bibr" href="#maraviroc.REF.6" rid="maraviroc.REF.6">6</a>).</p><p>Measurement of the CD4 count is useful before HIV treatment is started because the CD4 count provides information on the overall immune function of the patient. In the United States, antiretroviral therapy (ART) is now recommended for all HIV-infected patients, regardless of their CD4 count or viral load (<a class="bibr" href="#maraviroc.REF.7" rid="maraviroc.REF.7">7</a>), to keep viral loads at undetectable levels for as long as possible. In adults receiving optimized background treatment for infection with CCR5-tropic HIV-1, the addition of maraviroc leads to a greater increase in CD4 counts compared to the addition of placebo (<a class="bibr" href="#maraviroc.REF.1" rid="maraviroc.REF.1">1</a>).</p><p>HIV-1 most commonly uses either the CCR5 or CXCR4 co-receptors to enter its target cells (<a class="bibr" href="#maraviroc.REF.8" rid="maraviroc.REF.8">8</a>). Maraviroc is an effective antiretroviral agent in individuals who only harbor the CCR5-tropic HIV-1 virus. It is incapable of inhibiting infection against viruses that do not use CCR5 (i.e., CXCR-using virus or dual/mixed virus) (<a class="bibr" href="#maraviroc.REF.1" rid="maraviroc.REF.1">1</a>).</p><p>Maraviroc is metabolized by the cytochrome P450 system, mainly CYP3A, in the liver to inactive metabolites (<a class="bibr" href="#maraviroc.REF.9" rid="maraviroc.REF.9">9</a>, <a class="bibr" href="#maraviroc.REF.10" rid="maraviroc.REF.10">10</a>). As noted above, maraviroc must be used in combination with other antiretroviral medications; the recommended dosage of maraviroc depends on whether the co-medications are inhibitors or inducers of CYP3A (<a class="bibr" href="#maraviroc.REF.1" rid="maraviroc.REF.1">1</a>).</p></div><div id="maraviroc.Gene_CCR5"><h2 id="_maraviroc_Gene_CCR5_">Gene: <i>CCR5</i></h2><p>The chemokine (CC motif) receptor 5 (CCR5) is primarily expressed on the surface of white blood cells. Chemokines are a type of cytokine—they are small, secreted proteins that have a crucial role in the inflammatory response by helping immune cells migrate to areas of tissue damage. Other functions of chemokines include influencing the maturation of various immune cells and promoting the growth of new blood vessels.</p><p>Most chemokines have four characteristic cysteine residues in a conserved location, and they are classified into four families by the location of the first two cysteine residues: CXC, CC, C, and CX3C. For example, members of the “CC” cytokine family have two adjacent cysteine residues near their amino terminus.</p><p>The receptors for chemokines are G-protein coupled, seven-transmembrane domain receptors. Two of these receptors, CCR5 (binds CC chemokines) and CXCR4 (binds CXC chemokines), are also co-receptors used by HIV to enter human white blood cells. CCR5 is expressed on fewer cells (e.g., specific T cells, precursor cells (or macrophages) and dendritic cells) than CXCR4 (e.g., most immune cells, vascular endothelial cells, and neurons).</p><p>HIV-1 virus that uses the CCR5 co-receptor (CCR5-tropic) is more commonly found in the early stages of infection. It is also more common among individuals who have yet to receive treatment, and at least half of all infected individuals harbor only CCR5-tropic viruses throughout the course of infection. The CXCR4-tropic virus is more commonly found during later stages of disease and among individuals who have received HIV treatment. The presence of CXCR4-tropic virus is a predictor of lower CD4 count, a higher viral load, and a more rapid progression to AIDS (<a class="bibr" href="#maraviroc.REF.5" rid="maraviroc.REF.5">5</a>).</p><p>A variant of <i>CCR5</i>, <i>CCR5-Δ32</i> (<a href="/clinvar/variation/8184/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_000579.3:c.554_585del32</a>), contains a 32 bp deletion and codes a nonfunctional receptor that hinders the entry of CCR5-tropic virus in to cells. Individuals who have two copies of this allele are highly resistant to HIV infection, and although individuals who have one copy of the allele remain susceptible to HIV infection, the progression of HIV infection to AIDS is delayed (<a class="bibr" href="#maraviroc.REF.11" rid="maraviroc.REF.11">11</a>).</p><p>The <i>CCR5-Δ32</i> allele occurs at high frequency in European Caucasians (5%–14%) but is rare among African, Native American, and East Asian populations, suggesting that the allele may have conferred an evolutionary survival advantage (<a class="bibr" href="#maraviroc.REF.12" rid="maraviroc.REF.12">12</a>). Possible causes of a positive selection pressure include protection against the bubonic plague (<i>Yersinia pestis</i>) or smallpox (<i>Variola virus</i>) during the Middle Ages. However, other studies have found that the <i>CCR5-Δ32</i> allele arose long before this time and underwent neutral evolution (<a class="bibr" href="#maraviroc.REF.13" rid="maraviroc.REF.13">13</a>).</p></div><div id="maraviroc.Genetic_Testing"><h2 id="_maraviroc_Genetic_Testing_">Genetic Testing</h2><p>Testing of the HIV-1 virus (i.e., the virus, not the patient) should be carried out prior to initiation of treatment with maraviroc. A tropism assay is needed to identify individuals with CCR5-tropic HIV-1. The assay must be highly sensitive to detect low levels of CXCR4-tropic viruses. Maraviroc should not be prescribed if non-CCR5 variants (CXCR4-tropic or dual/mixed-tropic) are detected (<a class="bibr" href="#maraviroc.REF.1" rid="maraviroc.REF.1">1</a>, <a class="bibr" href="#maraviroc.REF.9" rid="maraviroc.REF.9">9</a>). HIV tropism can be determined by phenotype or genotype testing. Phenotypic assays can be performed using plasma RNA (if viral load is greater than 1000 copies/ml) or cell-associated DNA (if viral load is less than 1000 copies/ml). Phenotypic assays use replication-defective laboratory viruses that carry the complete cloned viral envelope proteins gp120 and gp41 derived from the patient. Phenotypic assays measure the ability of these pseudoviruses to infect CD4+ target cells that express either CCR5 or CXCR4 (<a class="bibr" href="#maraviroc.REF.7" rid="maraviroc.REF.7">7</a>).</p><p>Genotyping methods are used to predict which co-receptors on the cell are used by the virus rather than directly assessing tropism. Genotyping methods involve sequencing the third variable region (V3) of gp120 and using algorithms to predict co-receptor usage.</p><p>While phenotypic assays are still considered to be the gold standard, the use of genotyping to determine patient eligibility for maraviroc is increasing due to low cost, greater accessibility, and faster turnaround time for the results as compared to the other methods (<a class="bibr" href="#maraviroc.REF.14" rid="maraviroc.REF.14">14</a>, <a class="bibr" href="#maraviroc.REF.15" rid="maraviroc.REF.15">15</a>). Although there can be discrepancies between the results from phenotypic and genotypic assays, the correlation between genotypic assays and the clinical efficacy of maraviroc is improving (<a class="bibr" href="#maraviroc.REF.16" rid="maraviroc.REF.16">16</a>).</p><p>The NIH’s Genetic Testing Registry (GTR) displays genetic testing information for human genes and conditions, including tests for maraviroc response. These tests investigate the human genes that contribute to the pharmacokinetics of maraviroc, as opposed to the FDA-recommended genetic tests, which are tests for viral genes.</p></div><div id="maraviroc.Therapeutic_Recommendations_ba"><h2 id="_maraviroc_Therapeutic_Recommendations_ba_">Therapeutic Recommendations based on Genotype</h2><p><b>This section contains excerpted</b><sup><a href="#maraviroc.FN1">1</a></sup>
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<b>information on gene-based dosing recommendations. Neither this section nor other parts of this review contain the complete recommendations from the sources.</b></p><p><b>2016 Statement from the US Food and Drug Administration (FDA):</b> Prior to initiation of maraviroc, test all patients for CCR5 tropism using a highly sensitive tropism assay. Maraviroc is recommended for patients with only CCR5-tropic HIV-1 infection. Outgrowth of pre-existing low-level CXCR4- or dual/mixed-tropic HIV-1 not detected by tropism testing at screening has been associated with virologic failure while on maraviroc.</p><p><b>Please review the complete therapeutic recommendations that are located here: (</b><a class="bibr" href="#maraviroc.REF.1" rid="maraviroc.REF.1"><b>1</b></a><b>)</b>.</p></div><div id="maraviroc.Nomenclature"><h2 id="_maraviroc_Nomenclature_">Nomenclature</h2><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figmaravirocTe"><a href="/books/NBK279895/table/maraviroc.Te/?report=objectonly" target="object" title="Table" class="img_link icnblk_img" rid-ob="figobmaravirocTe"><img class="small-thumb" src="/corehtml/pmc/css/bookshelf/2.26/img/table-icon.gif" alt="Table Icon" /></a><div class="icnblk_cntnt"><h4 id="maraviroc.Te"><a href="/books/NBK279895/table/maraviroc.Te/?report=objectonly" target="object" rid-ob="figobmaravirocTe">Table</a></h4></div></div><p>Guidelines for the description and nomenclature of gene variations are available from the Human Genome Variation Society (HGVS) (<a class="bibr" href="#maraviroc.REF.17" rid="maraviroc.REF.17">17</a>)</p></div><div id="maraviroc.Acknowledgments"><h2 id="_maraviroc_Acknowledgments_">Acknowledgments</h2><p>The author would like to thank Aniwaa Owusu Obeng, PharmD, Assistant Professor, The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai; and Victoria M. Pratt, Ph.D., FACMG, Director, Pharmacogenomics Laboratory, Department of Medical and Molecular Genetics, Indiana University School of Medicine; for reviewing this summary.</p><p>
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<b>First edition:</b>
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</p><p>The author would like to thank Mark Wainberg, Professor of Molecular Biology/Virology at McGill University; and Timothy Henrich, Assistant Professor of Medicine, Brigham and Women’s Hospital.</p></div><div id="maraviroc.Version_History"><h2 id="_maraviroc_Version_History_">Version History</h2><p>To view an earlier version of this summary (18 March 2015), please click <a href="/books/NBK279895/bin/20150318maraviroc.pdf">here</a>.</p></div><div id="maraviroc.References"><h2 id="_maraviroc_References_">References</h2><dl class="temp-labeled-list"><dl class="bkr_refwrap"><dt>1.</dt><dd><div class="bk_ref" id="maraviroc.REF.1">SELZENTRY- maraviroc tablet, film coated SELZENTRY- maraviroc solution [package insert]. Freiberg, Germany: Pfizer Laboratories; 2016. Available from: <a href="https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=46f30ac5-c96b-429e-976d-8c5ee1c0761b" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">https://dailymed<wbr style="display:inline-block"></wbr>​.nlm<wbr style="display:inline-block"></wbr>​.nih.gov/dailymed/drugInfo<wbr style="display:inline-block"></wbr>​.cfm?setid=46f30ac5-c96b-429e-976d-8c5ee1c0761b</a>.</div></dd></dl><dl class="bkr_refwrap"><dt>2.</dt><dd><div class="bk_ref" id="maraviroc.REF.2">Sax P.E. Maraviroc for treatment-naive patients with HIV-1 infection: is the glass half empty or half full? <span><span class="ref-journal">J Infect Dis. </span>2010;<span class="ref-vol">201</span>(6):797–9.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/20151843" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 20151843</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>3.</dt><dd><div class="bk_ref" id="maraviroc.REF.3">Parra J., Portilla J., Pulido F., Sanchez-de la Rosa R., et al. Clinical utility of maraviroc. <span><span class="ref-journal">Clin Drug Investig. </span>2011;<span class="ref-vol">31</span>(8):527–42.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/21595497" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21595497</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>4.</dt><dd><div class="bk_ref" id="maraviroc.REF.4">Wyatt H., Herman O., Macartney M., Conibear T., et al. The utility of genotypic tropism testing in clinical practice. <span><span class="ref-journal">Int J STD AIDS. </span>2014.</span> [Epub ahead of print] [<a href="https://pubmed.ncbi.nlm.nih.gov/25147237" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25147237</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>5.</dt><dd><div class="bk_ref" id="maraviroc.REF.5">Goetz M.B., Leduc R., Kostman J.R., Labriola A.M., et al. Relationship between HIV coreceptor tropism and disease progression in persons with untreated chronic HIV infection. <span><span class="ref-journal">Journal of acquired immune deficiency syndromes. </span>2009;<span class="ref-vol">50</span>(3):259–66.</span> [<a href="/pmc/articles/PMC2670851/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2670851</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/19194318" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19194318</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>6.</dt><dd><div class="bk_ref" id="maraviroc.REF.6">Shepherd J.C., Jacobson L.P., Qiao W., Jamieson B.D., et al. Emergence and persistence of CXCR4-tropic HIV-1 in a population of men from the multicenter AIDS cohort study. <span><span class="ref-journal">The Journal of infectious diseases. </span>2008;<span class="ref-vol">198</span>(8):1104–12.</span> [<a href="/pmc/articles/PMC2753263/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2753263</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/18783316" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18783316</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>7.</dt><dd><div class="bk_ref" id="maraviroc.REF.7">UpToDate. Tricyclic and tetracyclic drugs: Pharmacology, administration, and side effects [Cited August 2, 2016]. Available from: <a href="https://www.uptodate.com/contents/tricyclic-and-tetracyclic-drugs-pharmacology-administration-and-side-effects?source=machineLearning&search=tricyclic+antidepressants&selectedTitle=1~150&sectionRank=2&anchor=H31#references" ref="pagearea=cite-ref&targetsite=external&targetcat=link&targettype=uri">https://www<wbr style="display:inline-block"></wbr>​.uptodate<wbr style="display:inline-block"></wbr>​.com/contents/tricyclic-and-tetracyclic-drugs-pharmacology-administration-and-side-effects?source<wbr style="display:inline-block"></wbr>​=machineLearning&search<wbr style="display:inline-block"></wbr>​=tricyclic+antidepressants&selectedTitle<wbr style="display:inline-block"></wbr>​=1~150&sectionRank<wbr style="display:inline-block"></wbr>​=2&anchor=H31#references</a>.</div></dd></dl><dl class="bkr_refwrap"><dt>8.</dt><dd><div class="bk_ref" id="maraviroc.REF.8">Michaud V., Bar-Magen T., Turgeon J., Flockhart D., et al. The dual role of pharmacogenetics in HIV treatment: mutations and polymorphisms regulating antiretroviral drug resistance and disposition. <span><span class="ref-journal">Pharmacological reviews. </span>2012;<span class="ref-vol">64</span>(3):803–33.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/22759796" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22759796</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>9.</dt><dd><div class="bk_ref" id="maraviroc.REF.9">Gaedigk A., Sangkuhl K., Whirl-Carrillo M., Klein T., et al. Prediction of CYP2D6 phenotype from genotype across world populations. <span><span class="ref-journal">Genet Med. </span>2016</span> [<a href="/pmc/articles/PMC5292679/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC5292679</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/27388693" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 27388693</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>10.</dt><dd><div class="bk_ref" id="maraviroc.REF.10">Woollard S.M., Kanmogne G.D. Maraviroc: a review of its use in HIV infection and beyond. <span><span class="ref-journal">Drug Des Devel Ther. </span>2015;<span class="ref-vol">9</span>:5447–68.</span> [<a href="/pmc/articles/PMC4598208/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4598208</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26491256" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26491256</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>11.</dt><dd><div class="bk_ref" id="maraviroc.REF.11">Ioannidis J.P., Rosenberg P.S., Goedert J.J., Ashton L.J., et al. Effects of CCR5-Delta32, CCR2-64I, and SDF-1 3'A alleles on HIV-1 disease progression: An international meta-analysis of individual-patient data. <span><span class="ref-journal">Annals of internal medicine. </span>2001;<span class="ref-vol">135</span>(9):782–95.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11694103" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11694103</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>12.</dt><dd><div class="bk_ref" id="maraviroc.REF.12">Stephens J.C., Reich D.E., Goldstein D.B., Shin H.D., et al. Dating the origin of the CCR5-Delta32 AIDS-resistance allele by the coalescence of haplotypes. <span><span class="ref-journal">American journal of human genetics. </span>1998;<span class="ref-vol">62</span>(6):1507–15.</span> [<a href="/pmc/articles/PMC1377146/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1377146</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/9585595" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 9585595</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>13.</dt><dd><div class="bk_ref" id="maraviroc.REF.13">Sabeti P.C., Walsh E., Schaffner S.F., Varilly P., et al. The case for selection at CCR5-Delta32. <span><span class="ref-journal">PLoS biology. </span>2005;<span class="ref-vol">3</span>(11):e378. </span> p. [<a href="/pmc/articles/PMC1275522/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC1275522</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/16248677" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16248677</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>14.</dt><dd><div class="bk_ref" id="maraviroc.REF.14">Kagan R.M., Johnson E.P., Siaw M., Biswas P., et al. A Genotypic Test for HIV-1 Tropism Combining Sanger Sequencing with Ultradeep Sequencing Predicts Virologic Response in Treatment-Experienced Patients. <span><span class="ref-journal">PloS one. </span>2012;<span class="ref-vol">7</span>(9):e46334. </span> p. [<a href="/pmc/articles/PMC3459909/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3459909</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/23029482" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23029482</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>15.</dt><dd><div class="bk_ref" id="maraviroc.REF.15">Vandekerckhove L.P., Wensing A.M., Kaiser R., Brun-Vezinet F., et al. European guidelines on the clinical management of HIV-1 tropism testing. <span><span class="ref-journal">The Lancet infectious diseases. </span>2011;<span class="ref-vol">11</span>(5):394–407.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/21429803" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21429803</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>16.</dt><dd><div class="bk_ref" id="maraviroc.REF.16">Perez-Olmeda M., Alcami J. Determination of HIV tropism and its use in the clinical practice. <span><span class="ref-journal">Expert Rev Anti Infect Ther. </span>2013;<span class="ref-vol">11</span>(12):1291–302.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/24191978" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24191978</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>17.</dt><dd><div class="bk_ref" id="maraviroc.REF.17">den Dunnen, J.T., R.
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Dalgleish, D.R.
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Maglott, R.K.
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Hart, et al. <span class="ref-title">HGVS Recommendations for the Description of Sequence Variants: 2016 Update. </span><span class="ref-journal">Hum Mutat</span>, 2016.37(6): p.564-9.
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[<a href="https://pubmed.ncbi.nlm.nih.gov/26931183" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26931183</span></a>]</div></dd></dl></dl></div><h2 id="NBK279895_footnotes">Footnotes</h2><dl class="temp-labeled-list small"><dl class="bkr_refwrap"><dt>
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<sup>1</sup>
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</dt><dd><div id="maraviroc.FN1"><p class="no_top_margin"> The FDA labels specific drug formulations. We have substituted the generic names for any drug labels in this excerpt. The FDA may not have labelled all formulations containing the generic drug.</p></div></dd></dl></dl><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK279895_pubdet_">Publication Details</h2><h3>Author Information and Affiliations</h3><p class="contrib-group"><h4>Authors</h4><span itemprop="author">Laura Dean</span>, MD<sup>1</sup>.</p><h4>Affiliations</h4><div class="affiliation"><sup>1</sup> NCBI<div><span class="email-label">Email: </span><a href="mailto:dev@null" data-email="vog.hin.mln.ibcn@naed" class="oemail">vog.hin.mln.ibcn@naed</a></div></div><h3>Publication History</h3><p class="small">Created: <span itemprop="datePublished">March 18, 2015</span>; Last Update: <span itemprop="dateModified">April 10, 2017</span>.</p><h3>Copyright</h3><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright Notice</a><p class="small">All Medical Genetics Summaries content, except where otherwise noted, is licensed under a Creative Commons <a href="https://creativecommons.org/licenses/by/4.0/" ref="pagearea=meta&targetsite=external&targetcat=link&targettype=uri">Attribution 4.0 International (CC BY 4.0)</a> license which permits copying, distribution, and adaptation of the work, provided the original work is properly cited and any changes from the original work are properly indicated. Any altered, transformed, or adapted form of the work may only be distributed under the same or similar license to this one.</p></div></div><h3>Publisher</h3><p><a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=books" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">National Center for Biotechnology Information (US)</a>, Bethesda (MD)</p><h3>NLM Citation</h3><p>Dean L. Maraviroc Therapy and CCR5 Genotype. 2015 Mar 18 [Updated 2017 Apr 10]. In: Pratt VM, Scott SA, Pirmohamed M, et al., editors. Medical Genetics Summaries [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2012-. <span class="bk_cite_avail"></span></p></div><div class="small-screen-prev"><a href="/books/n/gtrbook/lesinurad/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a></div><div class="small-screen-next"><a href="/books/n/gtrbook/mercaptopurine/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div></article><article data-type="table-wrap" id="figobmaravirocTe"><div id="maraviroc.Te" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK279895/table/maraviroc.Te/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__maraviroc.Te_lrgtbl__"><table><thead><tr><th id="hd_h_maraviroc.Te_1_1_1_1" rowspan="2" scope="col" colspan="1" headers="hd_h_maraviroc.Te_1_1_1_1" style="text-align:left;vertical-align:top;">Allele name</th><th id="hd_h_maraviroc.Te_1_1_1_2" rowspan="2" scope="col" colspan="1" headers="hd_h_maraviroc.Te_1_1_1_2" style="text-align:left;vertical-align:top;">Other name(s)</th><th id="hd_h_maraviroc.Te_1_1_1_3" colspan="2" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:top;">HGVS reference sequence</th><th id="hd_h_maraviroc.Te_1_1_1_4" rowspan="2" scope="col" colspan="1" headers="hd_h_maraviroc.Te_1_1_1_4" style="text-align:left;vertical-align:top;">dbSNP reference identifier for allele location</th></tr><tr><th headers="hd_h_maraviroc.Te_1_1_1_3" id="hd_h_maraviroc.Te_1_1_2_1" colspan="1" scope="colgroup" rowspan="1" style="text-align:left;vertical-align:top;">Coding</th><th headers="hd_h_maraviroc.Te_1_1_1_3" id="hd_h_maraviroc.Te_1_1_2_2" scope="col" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Protein</th></tr></thead><tbody><tr><td headers="hd_h_maraviroc.Te_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<i>CCR5delta32</i>
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</td><td headers="hd_h_maraviroc.Te_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"></td><td headers="hd_h_maraviroc.Te_1_1_1_3 hd_h_maraviroc.Te_1_1_2_1" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><a href="/clinvar/variation/8184/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NM_000579.3:c.554_585del32</a><br /><a href="/nuccore/154091327" class="bk_tag" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=nuccore">NM_001100168.1</a>:c.554_585del32</td><td headers="hd_h_maraviroc.Te_1_1_1_3 hd_h_maraviroc.Te_1_1_2_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;"><a href="/clinvar/variation/8184/" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">NP_000570.1:p.Ser185Ilefs</a><br /><a href="/protein/154091328/?report=GenPept" class="bk_tag" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=genpept">NP_001093638.1</a>:p.Ser185Ilefs</td><td headers="hd_h_maraviroc.Te_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="https://www.ncbi.nlm.nih.gov/snp/rs333" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">rs333</a>
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