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Human Immunodeficiency Virus Type-1 Episomal cDNA in Semen

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dc.contributor.author Xu, Chong en_US
dc.contributor.author Politch, Joseph A en_US
dc.contributor.author Mayer, Kenneth H en_US
dc.contributor.author Anderson, Deborah J en_US
dc.date.accessioned 2012-01-12T17:38:08Z
dc.date.available 2012-01-12T17:38:08Z
dc.date.copyright 2005 en_US
dc.date.issued 2005-10-11 en_US
dc.identifier.citation Xu, Chong, Joseph A Politch, Kenneth H Mayer, Deborah J Anderson. "Human immunodeficiency virus type-1 episomal cDNA in semen" AIDS Research and Therapy 2:9. (2005) en_US
dc.identifier.issn 1742-6405 en_US
dc.identifier.uri http://hdl.handle.net/2144/3407
dc.description.abstract BACKGROUND. Episomal 2-long terminal repeat (LTR) HIV-1 cDNA, a by-product of HIV-1 infection, is used in clinical trials as a marker for ongoing viral replication. It would be useful to employ 2-LTR cDNA to monitor cryptic HIV-1 infection in the genital tract of men on antiretroviral therapy (ART) to predict the evolution of sexually transmissible drug-resistant HIV-1, but studies thus far have failed to detect this marker in semen. The objectives of this study were: 1) to use a technique that maximizes DNA recovery from HIV-1 infected white blood cells in semen to determine if episomal 2-LTR cDNA is detectable in semen of ART-naïve men with other evidence of genital tract HIV-1 infection, and 2) to compare levels of HIV-1 2-LTR cDNA, RNA, and proviral DNA in semen from HIV-1+ men on ART. RESULTS. Using a somatic cell DNA extraction technique, 2-LTR cDNA was detected by PCR/ELISA in 4 out of 8 semen samples from ART-naïve men selected for other signs of seminal HIV-1 infection (positive controls). Southern blot and DNA sequencing confirmed that the amplified sequences were HIV-1 2-LTR cDNA; copy numbers ranged from 55 to 504 copies/sample. Two semen samples from a cohort of 22 HIV-1-infected men on dual nucleoside therapy, one with and one without detectable seminal HIV-1 RNA, were 2-LTR cDNA positive (336 and 8,560 copies/sample). Following addition of indinavir to the therapy regimen, no semen samples from 21 men with controlled peripheral and seminal viral loads were 2-LTR cDNA positive at 1 and 6 month time points, despite the persistence of HIV-1 proviral DNA+ semen cells and seminal cytomegalovirus (CMV) shedding in some cases. However, one individual who failed indinavir therapy and later developed distinct protease inhibitor (PI) drug resistance mutations in semen, maintained elevated levels of HIV-1 RNA and 2-LTR cDNA in semen. CONCLUSION. 2-LTR HIV-1 cDNA is detectable in semen of HIV-1-infected men. Two men on ART had 2-LTR HIV-1 cDNA in semen, suggesting that this marker may prove to be useful to monitor HIV-1 infection in the genital tract of men on ART to predict the evolution of drug resistance mutations in semen. en_US
dc.description.sponsorship National Institutes of Health (A1035564, DK072933) en_US
dc.language.iso en en_US
dc.publisher BioMed Central en_US
dc.rights Copyright 2005 Xu et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. en_US
dc.rights.uri http://creativecommons.org/licenses/by/2.0 en_US
dc.title Human Immunodeficiency Virus Type-1 Episomal cDNA in Semen en_US
dc.type article en_US
dc.identifier.doi 10.1186/1742-6405-2-9 en_US
dc.identifier.pubmedid 16219101 en_US
dc.identifier.pmcid 1277815 en_US


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Copyright 2005 Xu et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Except where otherwise noted, this item's license is described as Copyright 2005 Xu et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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