title: Increasing cerebrospinal fluid chemokine concentrations despite undetectable cerebrospinal fluid HIV RNA in HIV-1-infected patients receiving antiretroviral therapy.
abstract: Only limited data on cerebrospinal fluid (CSF) HIV-1 RNA responses and markers of local inflammation in CSF during antiretroviral therapy are available. HIV-RNA, soluble tumor necrosis factor (TNF)-receptor (sTNFr)-II, monocyte chemoattractant protein (MCP)-1, and interferon-gamma-inducible protein (IP)-10 were measured in the peripheral blood and CSF of 26 antiretroviral-naive HIV-1-positive patients, who were treated with ritonavir (RTV)/saquinavir (SQV) (n = 5), RTV/SQV/stavudine (d4T; n = 8) or zidovudine (AZT)/lamivudine (3TC)/abacavir/nevirapine/indinavir (n = 13). After 8 to 12 weeks of treatment, CSF HIV-RNA dropped to <400 copies/ml in 1 of 5 patients in the RTV/SQV group, 8 of 8 patients in the RTV/SQV/d4T group, and 9 of 10 patients in the five-drug group. CSF sTNFr-II and IP-10 levels increased in patients with detectable CSF HIV-RNA. However, increases in CSF chemokine and sTNFr-II concentrations were also observed in some patients with good CSF HIV-RNA responses. Moreover, CSF MCP-1 concentrations increased in the whole population after 2 months of treatment. Ongoing residual HIV replication in the central nervous system, which cannot be detected with CSF HIV-RNA measurements, may account for this phenomenon.
authors.affiliation: National AIDS Therapy Evaluation Center, Department of Internal Medicine, Amsterdam, The Netherlands.
authors.forename: E H
authors.initials: EH
authors.lastname: Gisolf
authors.forename: R M
authors.initials: RM
authors.lastname: van Praag
authors.forename: S
authors.initials: S
authors.lastname: Jurriaans
authors.forename: P
authors.initials: P
authors.lastname: Portegies
authors.forename: J
authors.initials: J
authors.lastname: Goudsmit
authors.forename: S A
authors.initials: SA
authors.lastname: Danner
authors.forename: J M
authors.initials: JM
authors.lastname: Lange
authors.forename: J M
authors.initials: JM
authors.lastname: Prins
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018932:Chemokine CCL2 / Q000097:blood / Q000134:cerebrospinal fluid; D054357:Chemokine CXCL10; D018925:Chemokines / Q000134:cerebrospinal fluid*; D019743:Chemokines, CXC / Q000097:blood / Q000134:cerebrospinal fluid; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D012367:RNA, Viral / Q000097:blood / Q000134:cerebrospinal fluid*; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*
chemical_list: D019380:Anti-HIV Agents; D018932:Chemokine CCL2; D054357:Chemokine CXCL10; D018925:Chemokines; D019743:Chemokines, CXC; D012367:RNA, Viral; D018124:Receptors, Tumor Necrosis Factor; D018894:Reverse Transcriptase Inhibitors