Suppression of cerebrospinal fluid HIV burden in antiretroviral naive patients on a potent four-drug antiretroviral regimen

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Abstract
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. Open study of HIV-infected subjects naive to therapy with protease inhibitors. Tertiary care referral center. Twenty-five participants were begun on indinavir, nevirapine, zidovudine, and lamivudine. 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. 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. 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.

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