OBJECTIVE: To determine the longitudinal response of HIV in the cerebrospinal fluid (CSF) to highly active antiretroviral therapy (HAART) and to investigate the levels of indinavir penetrating into the CSF. DESIGN: Open study of HIV-infected subjects naive to therapy with protease inhibitors. SETTING: Tertiary care referral center. SUBJECTS: Twenty-five participants were begun on indinavir, nevirapine, zidovudine, and lamivudine. INTERVENTIONS: Lumbar punctures were performed prior to therapy and 2 and 6 months after beginning therapy. Plasma and CSF were assayed for routine cell counts, chemistries, HIV load and indinavir levels. RESULTS: Twenty-two subjects had CSF HIV RNA level data available at all three time points, three others at baseline and 2 months. At month 2 of therapy, nine of 25 (36%) subjects had CSF HIV RNA levels > 50 HIV RNA copies/ml. By 6 months, all 22 subjects had CSF HIV RNA levels < 50 HIV RNA copies/ml. CSF white blood cell counts fell from a baseline mean of 5.3 x 10(6)/l to 1.9 x 10(6)/l (P = 0.013) at 6 months. Plasma indinavir levels declined rapidly while CSF levels remained stable throughout the 8-h dosing interval. The median CSF indinavir level was 71 ng/ml, approximating the upper limit of the 95% inhibitory concentration for indinavir against HIV-1. CONCLUSIONS: CSF HIV RNA levels cannot be expected to fall below 50 HIV RNA copies/ml even after 2 months of therapy on HAART. Prolonged therapy may be required to suppress HIV levels within the central nervous system.
OBJECTIVE: To determine the longitudinal response of HIV in the cerebrospinal fluid (CSF) to highly active antiretroviral therapy (HAART) and to investigate the levels of indinavir penetrating into the CSF. DESIGN: Open study of HIV-infected subjects naive to therapy with protease inhibitors. SETTING: Tertiary care referral center. SUBJECTS: Twenty-five participants were begun on indinavir, nevirapine, zidovudine, and lamivudine. INTERVENTIONS: Lumbar punctures were performed prior to therapy and 2 and 6 months after beginning therapy. Plasma and CSF were assayed for routine cell counts, chemistries, HIV load and indinavir levels. RESULTS: Twenty-two subjects had CSF HIV RNA level data available at all three time points, three others at baseline and 2 months. At month 2 of therapy, nine of 25 (36%) subjects had CSF HIV RNA levels > 50 HIV RNA copies/ml. By 6 months, all 22 subjects had CSF HIV RNA levels < 50 HIV RNA copies/ml. CSF white blood cell counts fell from a baseline mean of 5.3 x 10(6)/l to 1.9 x 10(6)/l (P = 0.013) at 6 months. Plasma indinavir levels declined rapidly while CSF levels remained stable throughout the 8-h dosing interval. The median CSF indinavir level was 71 ng/ml, approximating the upper limit of the 95% inhibitory concentration for indinavir against HIV-1. CONCLUSIONS: CSF HIV RNA levels cannot be expected to fall below 50 HIV RNA copies/ml even after 2 months of therapy on HAART. Prolonged therapy may be required to suppress HIV levels within the central nervous system.
Authors: Edward R Hammond; Rosa M Crum; Glenn J Treisman; Shruti H Mehta; Christina M Marra; David B Clifford; Susan Morgello; David M Simpson; Benjamin B Gelman; Ronald J Ellis; Igor Grant; Scott L Letendre; Justin C McArthur Journal: Am J Epidemiol Date: 2014-06-24 Impact factor: 4.897
Authors: Elizabeth Sinclair; Rollie Ronquillo; Nicole Lollo; Steven G Deeks; Peter Hunt; Constantin T Yiannoutsos; Serena Spudich; Richard W Price Journal: J Acquir Immune Defic Syndr Date: 2008-04-15 Impact factor: 3.731
Authors: Aylin Yilmaz; Arash Izadkhashti; Richard W Price; Patrick W Mallon; Marc De Meulder; Philip Timmerman; Magnus Gisslén Journal: AIDS Res Hum Retroviruses Date: 2009-04 Impact factor: 2.205
Authors: Serena S Spudich; Annelie C Nilsson; Nicole D Lollo; Teri J Liegler; Christos J Petropoulos; Steven G Deeks; Ellen E Paxinos; Richard W Price Journal: BMC Infect Dis Date: 2005-11-02 Impact factor: 3.090