title: Efficacy of nelfinavir-based treatment in the central nervous system of HIV-1 infected patients.
abstract: We studied the HIV-1 load and nelfinavir (NFV) concentrations in cerebrospinal fluid (CSF) after long-term successful NFV-based therapy, using ultrasensitive methods of detection. 19 patients without virological failure in plasma, who had been treated with 2 nucleoside analogue reverse transcripaste inhibitors (NRTI) and NFV for a minimum of 18 months were included. HIV-RNA was determined in plasma and CSF using an ultrasensitive method (<2 copies/ml). Total and free concentrations of NFV were analysed using high liquid chromatography with UV-light detection. 12 out of 19 (63%) patients had <2 copies HIV-RNA/ml in CSF. Seven subjects ranged between 3 and 39 copies/ml, 2 of whom had a slightly higher viral load in CSF than in plasma. NFV was detected in CSF in 16 out of 18 patients analysed and was quantifiable in 8 patients, at concentrations ranging from 6 to 29 nM. There was no correlation between NFV concentration and HIV-RNA levels. Long-term therapy with NFV + 2 NRTI showed no increased rate of virological treatment failure within the central nervous system (CNS) in compliant patients, despite earlier reports of lack of NFV penetration to CNS. Using a highly sensitive method, NFV was detected and quantified in the CSF, although at low values, which could have contributed to the high anti-HIV-1 efficacy of the therapy seen in our subjects.
authors.affiliation: Divisions of Infectious Diseases, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden. olle.karlstrom@medhs.ki.se
authors.forename: Olle
authors.initials: O
authors.lastname: Karlström
authors.forename: Lars
authors.initials: L
authors.lastname: Ståhle
authors.forename: Luc
authors.initials: L
authors.lastname: Perrin
authors.forename: Heike
authors.initials: H
authors.lastname: Tegude
authors.forename: Anders
authors.initials: A
authors.lastname: Sönnerborg
mesh_terms: D019380:Anti-HIV Agents / Q000134:cerebrospinal fluid / Q000627:therapeutic use*; D002555:Cerebrospinal Fluid / Q000821:virology; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000134:cerebrospinal fluid / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D008297:Male; D019888:Nelfinavir / Q000134:cerebrospinal fluid / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood / Q000134:cerebrospinal fluid; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019888:Nelfinavir