Continuing intrathecal immunoactivation despite two years of effective antiretroviral therapy against HIV-1 infection

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Abstract
To study the effect of antiretroviral combination treatment on intrathecal immunoactivation in HIV-1 infection. Lumbar punctures were performed at baseline, and after 4 months, 1 and 2 years on 30 neurologically asymptomatic, treatment-naive HIV-1-infected patients started on antiretroviral treatment with three or more drugs. Levels of neopterin, β2-microglobulin and HIV-1 RNA were measured in cerebrospinal fluid (CSF) and blood. All patients continued the study until the 4-month follow-up, although seven discontinued before the 1-year control, and an additional five discontinued before the control after 2 years. Neopterin, β2-microglobulin and HIV-1 RNA decreased significantly both in CSF and blood, but although 100% of the patients decreased their CSF concentrations of β2-microglobulin and HIV-1 RNA to normal levels, only 55% had normal CSF neopterin concentrations after 2 years treatment. In addition to CSF viral load, antiretroviral combination therapy substantially decreases the intrathecal immunoactivation as reflected by CSF neopterin and β2-microglobulin in neuroasymptomatic HIV-1-infected patients. However, almost half of the patients still have slightly increased CSF neopterin concentrations after 2 years of effective treatment, which might reflect an ongoing low-grade viral replication in brain tissue.