{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T21:56:06Z","timestamp":1762898166477},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2006,3,27]],"date-time":"2006-03-27T00:00:00Z","timestamp":1143417600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Infect Dis"],"published-print":{"date-parts":[[2006,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>The way various antiretroviral drugs and drug combinations affect HIV-1 infection in the central nervous system is still largely unknown. The aim of this study was to determine the cerebrospinal fluid (CSF) steady-state concentrations of saquinavir and nelfinavir in relation to plasma concentrations, and to study their effect in combination with two nucleoside reverse transcriptase inhibitors (NRTIs) on CSF viral loads, intrathecal immunoactivation, and blood-brain barrier integrity.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Paired CSF and plasma samples from 8 antiretroviral-na\u00efve HIV-1 infected patients starting combination therapy with saquinavir, nelfinavir, and two nucleoside analogues were collected prior to treatment, and again after approximately 12 and 48 weeks of antiretroviral therapy. Additional plasma samples were taken at weeks 2, 4, 8, 24, and 36. The concentrations of protease inhibitors were analysed, as were levels of HIV-1 RNA, CD4+ T-cell count, \u03b22-microglobulin, neopterin, albumin ratio, IgG index, and monocytic cell count.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>None of the patients in the study presented with HIV-1 RNA &lt; 50 copies\/mL in CSF or plasma prior to treatment, compared to 5\/7 at the end of the study. Signs of cell-mediated intrathecal immunoactivation, measured by neopterin and \u03b22-microglobulin, decreased significantly in both CSF and serum, although only 1\/7 reached normal CSF neopterin levels after 48 weeks of treatment. There was no significant reduction of albumin ratio, IgG index or CSF monocytic cell count. Saquinavir median (range) concentrations were &lt; 2.5 (&lt; 2.5\u201396.0) nM unbound in plasma, and &lt; 2.5 (&lt; 2.5\u20139.0) nM total in CSF. Nelfinavir median (range) concentrations were 10.0 (&lt; 2.0\u201331.0) nM unbound in plasma, and &lt; 2.0 (&lt; 2.0\u201323.0) nM total in CSF. Saquinavir and nelfinavir were detectable in 7\/15 and 9\/15 CSF samples, respectively.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Saquinavir and nelfinavir, in combination with two NRTIs, decrease the CSF viral load and, to a lesser extent, intrathecal immunoactivation. We found reasonably high CSF concentrations of nelfinavir, but suboptimal concentrations of saquinavir.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2334-6-63","type":"journal-article","created":{"date-parts":[[2006,4,6]],"date-time":"2006-04-06T12:50:36Z","timestamp":1144327836000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Cerebrospinal fluid HIV-1 RNA, intrathecal immunoactivation, and drug concentrations after treatment with a combination of saquinavir, nelfinavir, and two nucleoside analogues: the M61022 study"],"prefix":"10.1186","volume":"6","author":[{"given":"Aylin","family":"Yilmaz","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dietmar","family":"Fuchs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lars","family":"Hagberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrika","family":"Nillroth","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lars","family":"St\u00e5hle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan-Olof","family":"Svensson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Magnus","family":"Gissl\u00e9n","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2006,3,27]]},"reference":[{"key":"327_CR1","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1097\/00002030-199305000-00010","volume":"7","author":"P Portegies","year":"1993","unstructured":"Portegies P, Enting RH, de Gans J, Algra PR, Derix MM, Lange JM, Goudsmit J: Presentation and course of AIDS dementia complex: 10 years of follow-up in Amsterdam, The Netherlands. 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