{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:41:29Z","timestamp":1791290489307,"version":"4.3.0"},"reference-count":33,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2003,1,1]],"date-time":"2003-01-01T00:00:00Z","timestamp":1041379200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2003,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>The variable penetration of antiretroviral drugs into sanctuary sites may contribute to the differential evolution of human immunodeficiency virus (HIV) and the emergence of drug resistance. We evaluated the penetration of indinavir, nelfinavir, and lopinavir-ritonavir (lopinavir\/r) in the central nervous system, genital tract, and lymphoid tissue and assessed the correlation with residual viral replication. Plasma, cerebrospinal fluid (CSF), semen, and lymph node biopsy samples were collected from 41 HIV-infected patients on stable highly active antiretroviral therapy regimens to determine drug concentrations and HIV RNA levels. When HIV RNA was detectable, sequencing of the reverse transcriptase and protease genes was performed. Ratios of the concentration in semen\/concentration in plasma were 1.9 for indinavir, 0.08 for nelfinavir, and 0.07 for lopinavir. Only indinavir was detectable in CSF, with a concentration in CSF\/concentration in plasma ratio of 0.17. Differential penetration into lymphoid tissue was observed, with concentration in lymph node tissue\/concentration in plasma ratios of 2.07, 0.58, and 0.21 for indinavir, nelfinavir, and lopinavir, respectively. HIV RNA levels were &lt;50 copies\/ml in all CSF samples of patients in whom HIV RNA was not detectable in plasma. HIV RNA was detectable in the semen of three patients (two patients receiving nelfinavir and one patient receiving lopinavir\/r), and its detection was associated with multiple resistance mutations, while the viral load in plasma was undetectable. HIV RNA was detectable in all lymph node tissue samples. Differential drug penetration was observed among the three protease inhibitors in the sanctuary sites, but there was no correlation between drug levels and HIV RNA levels, suggesting that multiple factors are involved in the persistence of viral reservoirs. Further studies are required to clarify the role and clinical relevance of drug penetration in sanctuaries in terms of long-term efficacy and drug resistance.<\/jats:p>","DOI":"10.1128\/aac.47.1.238-243.2003","type":"journal-article","created":{"date-parts":[[2002,12,24]],"date-time":"2002-12-24T04:39:08Z","timestamp":1040704748000},"page":"238-243","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":152,"title":["Discrepancies between Protease Inhibitor Concentrations and Viral Load in Reservoirs and Sanctuary Sites in Human Immunodeficiency Virus-Infected Patients"],"prefix":"10.1128","volume":"47","author":[{"given":"Caroline","family":"Solas","sequence":"first","affiliation":[{"name":"Laboratory of Pharmacokinetics, University Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Lafeuillade","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, General Hospital, Toulon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Halfon","sequence":"additional","affiliation":[{"name":"Laboratory of Virology Alphabio, Marseilles"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ste\u0301phane","family":"Chadapaud","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, General Hospital, Toulon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilles","family":"Hittinger","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, General Hospital, Toulon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Lacarelle","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacokinetics, University Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/S0165-0378(98)00056-4","volume":"41","year":"1998","unstructured":"Byrn, R. A., and A. A. Kiessling. 1998. Analysis of human immunodeficiency virus in semen: indication of a genetically distinct virus reservoir. J. Reprod. Immunol.41:161-176.","journal-title":"J. Reprod. Immunol."},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/387183a0"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.24.13193"},{"key":"e_1_3_2_5_2","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1097\/00002030-199905280-00018","volume":"13","year":"1999","unstructured":"DiStefano, M., J. R. Fiore, L. Monno, A. Lepera, G. Pastore, and G. Angarano. 1999. Detection of multiple drug-resistance-associated pol mutations in cervicovaginal secretions from women. 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