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Increasing Cerebrospinal Fluid Chemokine Concentrations Despite Undetectable Cerebrospinal Fluid HIV RNA in HIV-1-Infected Patients Receiving Antiretroviral Therapy

Gisolf Elisabeth H.; van Praag, Rieneke M.E.; Jurriaans, Suzanne; Portegies, Peter; Goudsmit, Jaap; Danner, Sven A.; Lange, Joep M.A.; Prins, Jan M.
JAIDS Journal of Acquired Immune Deficiency Syndromes: December 15th, 2000
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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-γ-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.

Address correspondence and reprint requests to Jan M. Prins, National AIDS Therapy Evaluation Center, Academic Medical Center, F4-217, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands; e-mail:

Manuscript received April 25, 2000; accepted August 22, 2000.

© 2000 Lippincott Williams & Wilkins, Inc.