Improvement in immune parameters and human immunodeficiency virus-1 viral response in individuals treated with 16α-bromoepiandrosterone (HE2000)
A randomised, double-blind, placebo-controlled study examined the safety, tolerance, immunological effect and anti-human immunodeficiency virus (HIV) activity of sub-cutaneously administered HE2000 (16α-bromoepiandrosterone) as monotherapy in treatment-naïve patients with HIV-1. Twenty-four patients...
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| Veröffentlicht in: | Clinical microbiology and infection 2006-11, Vol.12 (11), p.1082-1088 |
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| container_title | Clinical microbiology and infection |
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| creator | Reading, C. Dowding, C. Schramm, B. Garsd, A. Onizuka-Handa, N. Stickney, D. Frincke, J. |
| description | A randomised, double-blind, placebo-controlled study examined the safety, tolerance, immunological effect and anti-human immunodeficiency virus (HIV) activity of sub-cutaneously administered HE2000 (16α-bromoepiandrosterone) as monotherapy in treatment-naïve patients with HIV-1. Twenty-four patients received five sequential daily doses of 50 or 100 mg of HE2000 or placebo every 6 weeks for up to three courses, and were followed thereafter for 3 months. HE2000 was safe, with transient injection site reactions being the main side-effect. Peripheral blood samples, collected serially, were analysed for changes in immune cell phenotypes. Significant increases were observed in the numbers of circulating dendritic cells, early activated (CD69+CD25–) CD8 T-cells and T-NK cells after administration of 50-mg doses of HE2000 (p |
| doi_str_mv | 10.1111/j.1469-0691.2006.01520.x |
| format | Article |
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Twenty-four patients received five sequential daily doses of 50 or 100 mg of HE2000 or placebo every 6 weeks for up to three courses, and were followed thereafter for 3 months. HE2000 was safe, with transient injection site reactions being the main side-effect. Peripheral blood samples, collected serially, were analysed for changes in immune cell phenotypes. Significant increases were observed in the numbers of circulating dendritic cells, early activated (CD69+CD25–) CD8 T-cells and T-NK cells after administration of 50-mg doses of HE2000 (p <0.05). Gene expression in peripheral blood mononuclear cells was analysed by real-time RT-PCR. Before treatment, HIV-1-infected patients had significantly elevated transcripts for a number of inflammatory mediators (p <0.012). After 50 mg or 100 mg HE2000, but not after placebo, there were significant sustained decreases in IL-1β, TNF-α, IL-6 and Cox-2 transcripts (p <0.05). There were no significant differences in CD4 cell numbers, although patients receiving 50-mg doses demonstrated a significant decrease in viral load (– 0.6 log; p <0.01). Anti-HIV-1 T-cell responses were analysed serially using GAG-peptides to stimulate cytoplasmic IFN-γ responses. After three courses, the 50-mg dose group demonstrated a significant increase in CD8 T-cell response against two distinct GAG peptide pools (p <0.03). These findings suggest that immune-based therapies may be able to impact viral load by decreasing inflammation and/or stimulating CD8 T-cells.</description><identifier>ISSN: 1198-743X</identifier><identifier>EISSN: 1469-0691</identifier><identifier>DOI: 10.1111/j.1469-0691.2006.01520.x</identifier><language>eng</language><publisher>Oxford, UK: Elsevier Ltd</publisher><subject>16α-bromoepiandrosterone ; AIDS ; Biological and medical sciences ; HE2000 ; human immunodeficiency virus ; Human immunodeficiency virus 1 ; immune stimulation ; Infectious diseases ; Medical sciences ; therapy</subject><ispartof>Clinical microbiology and infection, 2006-11, Vol.12 (11), p.1082-1088</ispartof><rights>2006 European Society of Clinical Infectious Diseases</rights><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5160-70cd75517d3923427cd770804402393ae8e8298da321a740beb40a678013b02e3</citedby><cites>FETCH-LOGICAL-c5160-70cd75517d3923427cd770804402393ae8e8298da321a740beb40a678013b02e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1469-0691.2006.01520.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1469-0691.2006.01520.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18136846$$DView record in Pascal Francis$$Hfree_for_read</backlink></links><search><creatorcontrib>Reading, C.</creatorcontrib><creatorcontrib>Dowding, C.</creatorcontrib><creatorcontrib>Schramm, B.</creatorcontrib><creatorcontrib>Garsd, A.</creatorcontrib><creatorcontrib>Onizuka-Handa, N.</creatorcontrib><creatorcontrib>Stickney, D.</creatorcontrib><creatorcontrib>Frincke, J.</creatorcontrib><title>Improvement in immune parameters and human immunodeficiency virus-1 viral response in individuals treated with 16α-bromoepiandrosterone (HE2000)</title><title>Clinical microbiology and infection</title><description>A randomised, double-blind, placebo-controlled study examined the safety, tolerance, immunological effect and anti-human immunodeficiency virus (HIV) activity of sub-cutaneously administered HE2000 (16α-bromoepiandrosterone) as monotherapy in treatment-naïve patients with HIV-1. Twenty-four patients received five sequential daily doses of 50 or 100 mg of HE2000 or placebo every 6 weeks for up to three courses, and were followed thereafter for 3 months. HE2000 was safe, with transient injection site reactions being the main side-effect. Peripheral blood samples, collected serially, were analysed for changes in immune cell phenotypes. Significant increases were observed in the numbers of circulating dendritic cells, early activated (CD69+CD25–) CD8 T-cells and T-NK cells after administration of 50-mg doses of HE2000 (p <0.05). Gene expression in peripheral blood mononuclear cells was analysed by real-time RT-PCR. Before treatment, HIV-1-infected patients had significantly elevated transcripts for a number of inflammatory mediators (p <0.012). After 50 mg or 100 mg HE2000, but not after placebo, there were significant sustained decreases in IL-1β, TNF-α, IL-6 and Cox-2 transcripts (p <0.05). There were no significant differences in CD4 cell numbers, although patients receiving 50-mg doses demonstrated a significant decrease in viral load (– 0.6 log; p <0.01). Anti-HIV-1 T-cell responses were analysed serially using GAG-peptides to stimulate cytoplasmic IFN-γ responses. After three courses, the 50-mg dose group demonstrated a significant increase in CD8 T-cell response against two distinct GAG peptide pools (p <0.03). These findings suggest that immune-based therapies may be able to impact viral load by decreasing inflammation and/or stimulating CD8 T-cells.</description><subject>16α-bromoepiandrosterone</subject><subject>AIDS</subject><subject>Biological and medical sciences</subject><subject>HE2000</subject><subject>human immunodeficiency virus</subject><subject>Human immunodeficiency virus 1</subject><subject>immune stimulation</subject><subject>Infectious diseases</subject><subject>Medical sciences</subject><subject>therapy</subject><issn>1198-743X</issn><issn>1469-0691</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><recordid>eNqNUc1u1DAQthCVKAvv4AuoHBLGceI4Bw6wKrTSol5aiZvljWdVr_KHnWy7j9FH4UV4Jia7K7gBvsxY833f_HyMcQGpoPd-m4pcVQmoSqQZgEpBFBmkj8_Y-e_Cc8pFpZMyl99esJcxbgEgkzI_Z0_X7RD6HbbYjdx33Lft1CEfbLAtjhgit53j91NrT7Xe4cbXHrt6z3c-TDERc7QNDxiHvot4kOmc33k32SbyMaAd0fEHP95zoX7-SNahb3scPEmHPlKXnlpeXF3S_PDuFTvbEA1fn-KC3X2-vF1eJaubL9fLj6ukLoSCpITalUUhSierTOZZSd8SNOQ5bVZJixp1VmlnZSZsmcMa1zlYVWoQcg0ZygV7e9Sl_b9PGEfT-lhj09gO-ykaURUZXVIS8OLvwEIpnQtF110wfYTWtFcMuDFD8K0NeyPAzHaZrZldMbMrZrbLHOwyj0R9c-piY22bTbBd7eMfvhaSuijCfTjiHnyD-__WN8vV1zkj_qcjH-m2O4_BxIOb6HzAejSu9_8e9hcoQr6f</recordid><startdate>200611</startdate><enddate>200611</enddate><creator>Reading, C.</creator><creator>Dowding, C.</creator><creator>Schramm, B.</creator><creator>Garsd, A.</creator><creator>Onizuka-Handa, N.</creator><creator>Stickney, D.</creator><creator>Frincke, J.</creator><general>Elsevier Ltd</general><general>Blackwell Publishing Ltd</general><general>Blackwell</general><scope>6I.</scope><scope>AAFTH</scope><scope>IQODW</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7U9</scope><scope>H94</scope></search><sort><creationdate>200611</creationdate><title>Improvement in immune parameters and human immunodeficiency virus-1 viral response in individuals treated with 16α-bromoepiandrosterone (HE2000)</title><author>Reading, C. ; Dowding, C. ; Schramm, B. ; Garsd, A. ; Onizuka-Handa, N. ; Stickney, D. ; Frincke, J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5160-70cd75517d3923427cd770804402393ae8e8298da321a740beb40a678013b02e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>16α-bromoepiandrosterone</topic><topic>AIDS</topic><topic>Biological and medical sciences</topic><topic>HE2000</topic><topic>human immunodeficiency virus</topic><topic>Human immunodeficiency virus 1</topic><topic>immune stimulation</topic><topic>Infectious diseases</topic><topic>Medical sciences</topic><topic>therapy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Reading, C.</creatorcontrib><creatorcontrib>Dowding, C.</creatorcontrib><creatorcontrib>Schramm, B.</creatorcontrib><creatorcontrib>Garsd, A.</creatorcontrib><creatorcontrib>Onizuka-Handa, N.</creatorcontrib><creatorcontrib>Stickney, D.</creatorcontrib><creatorcontrib>Frincke, J.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Pascal-Francis</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Clinical microbiology and infection</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Reading, C.</au><au>Dowding, C.</au><au>Schramm, B.</au><au>Garsd, A.</au><au>Onizuka-Handa, N.</au><au>Stickney, D.</au><au>Frincke, J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Improvement in immune parameters and human immunodeficiency virus-1 viral response in individuals treated with 16α-bromoepiandrosterone (HE2000)</atitle><jtitle>Clinical microbiology and infection</jtitle><date>2006-11</date><risdate>2006</risdate><volume>12</volume><issue>11</issue><spage>1082</spage><epage>1088</epage><pages>1082-1088</pages><issn>1198-743X</issn><eissn>1469-0691</eissn><abstract>A randomised, double-blind, placebo-controlled study examined the safety, tolerance, immunological effect and anti-human immunodeficiency virus (HIV) activity of sub-cutaneously administered HE2000 (16α-bromoepiandrosterone) as monotherapy in treatment-naïve patients with HIV-1. Twenty-four patients received five sequential daily doses of 50 or 100 mg of HE2000 or placebo every 6 weeks for up to three courses, and were followed thereafter for 3 months. HE2000 was safe, with transient injection site reactions being the main side-effect. Peripheral blood samples, collected serially, were analysed for changes in immune cell phenotypes. Significant increases were observed in the numbers of circulating dendritic cells, early activated (CD69+CD25–) CD8 T-cells and T-NK cells after administration of 50-mg doses of HE2000 (p <0.05). Gene expression in peripheral blood mononuclear cells was analysed by real-time RT-PCR. Before treatment, HIV-1-infected patients had significantly elevated transcripts for a number of inflammatory mediators (p <0.012). After 50 mg or 100 mg HE2000, but not after placebo, there were significant sustained decreases in IL-1β, TNF-α, IL-6 and Cox-2 transcripts (p <0.05). 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| source | Wiley-Blackwell Journals; Alma/SFX Local Collection; EZB Electronic Journals Library |
| subjects | 16α-bromoepiandrosterone AIDS Biological and medical sciences HE2000 human immunodeficiency virus Human immunodeficiency virus 1 immune stimulation Infectious diseases Medical sciences therapy |
| title | Improvement in immune parameters and human immunodeficiency virus-1 viral response in individuals treated with 16α-bromoepiandrosterone (HE2000) |
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