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This increase may be a result of dissemination of lung-derived HIV-1 isolates from sites of<jats:italic>Mycobacterium tuberculosis<\/jats:italic>infection and\/or the systemic activation of the immune system in response to TB. To distinguish between these two mechanisms, blood and pleural fluid samples were obtained from HIV-1-infected patients with active pleural TB in Kampala, Uganda (CD4 cell counts of 34 to 705 cells\/\u03bcl, HIV-1 plasma loads of 2,400 to 280,000 RNA copies\/ml, and HIV-1 pleural loads of 7,600 to 4,500,000 RNA copies\/ml). The C2-C3 coding region of HIV-1<jats:italic>env<\/jats:italic>was PCR amplified from lysed peripheral blood mononuclear cells and pleural fluid mononuclear cells and reverse transcriptase-PCR amplified from plasma and pleural fluid HIV-1 virions of eight HIV-1 patients with pleural TB. Phylogenetic and phenetic analyses revealed a compartmentalization of HIV-1 quasispecies between blood and pleural space in four of eight patients, with migration events between the compartments. There was a trend for a greater genetic heterogeneity in the pleural space, which may be the result of an<jats:italic>M. tuberculosis<\/jats:italic>-mediated increase in HIV-1 replication and\/or selection pressure at the site of infection. Collectively, these findings suggest that HIV-1 quasispecies in the<jats:italic>M. tuberculosis<\/jats:italic>-infected pleural space may leak into the systemic circulation and lead to increased systemic HIV-1 heterogeneity during TB.<\/jats:p>","DOI":"10.1128\/jvi.76.4.1697-1706.2002","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T09:55:53Z","timestamp":1027763753000},"page":"1697-1706","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":61,"title":["Human Immunodeficiency Virus Type 1 (HIV-1)Quasispecies at the Sites of<i>Mycobacterium tuberculosis<\/i>InfectionContribute to Systemic HIV-1 Heterogeneity"],"prefix":"10.1128","volume":"76","author":[{"given":"Kalonji R.","family":"Collins","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Department ofMedicine"},{"name":"Molecular Virology Training Program,Case Western Reserve University, Cleveland, Ohio 44106"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel E.","family":"Quin\u0303ones-Mateu","sequence":"additional","affiliation":[{"name":"Department of Virology, Lerner Research Institute,Cleveland Clinic Foundation, Cleveland, Ohio 44195"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mianda","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department ofMedicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry","family":"Luzze","sequence":"additional","affiliation":[{"name":"National Tuberculosis Treatment Centre, MulagoHospitals, Makerere University, Kampala, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John L.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department ofMedicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Hirsch","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department ofMedicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahra","family":"Toossi","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department ofMedicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric J.","family":"Arts","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department ofMedicine"},{"name":"Molecular Virology Training Program,Case Western Reserve University, Cleveland, Ohio 44106"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-199507000-00002"},{"key":"e_1_3_2_3_2","doi-asserted-by":"crossref","first-page":"7216","DOI":"10.4049\/jimmunol.151.12.7216","volume":"151","year":"1993","unstructured":"Antony, V. 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