Background:  Just as in plasma, HAART effectively reduces HIV RNA in cerebrospinal fluid (CSF). The effect on intrathecal immunoactivation is less well studied. We have earlier found that a substantial number of patients still have evidence of intrathecal immunoactivation after as long as 2 years of treatment.

Methods:  To assess the long-term effect of HAART on central nervous system immune activation, we measured CSF neopterin (RIA, IMMU test) and immunoglobulin G (IgG) index (CSF IgG (mg/L) / serum IgG [g/L])/(CSF albumin [mg/L] / serum albumin [g/L]) in 16 HIV-infected patients treated with HAART with plasma HIV RNA <50 copies/mL for at least 4 years (1 blip allowed during the period, i.e. single RNA 50 to 1000). CSF from before treatment initiation was, in addition, available in 10 patients.

Results:  All 16 patients had HIV RNA <50 copies/mL in plasma and CSF during treatment. The CSF neopterin concentration was a median of 17.4 (range 6.7 to 55.3) nmol/L before treatment and 6.3 (3.7 to 10.7) nmol/L after >4 years of HAART, 13 of 16 (81%) still had CSF neopterin above the upper normal reference value (4.3 nmol/L) after 4 years compared with 10 of 10 before treatment. The IgG index was 0.73 (0.43 to 1.99) before treatment and 0.67 (0.46 to 3.05) during HAART with 8 of 10 and 7 of 16 (44%) with abnormal levels (>0.62) before and during HAART.

Conclusions:  HAART significantly decreases intrathecal immunoactivation, but despite effective treatment for >4 years, with HIV RNA <50 copies/mL, a substantial proportion of patients continue to exhibit signs of central nervous system macrophage / microglia activation (neopterin) and intrathecal immunoglobulin production (IgG index). Whether these findings reflect ongoing low-grade viral replication in brain tissue or unspecific immunoactivation is not settled.