Background:  We report 10 cases of HIV-related meningoencephalitis in patients on ART with discordant plasma/central nervous system HIV RNA.

Methods:  We identified 10 patients who had experienced acute or sub-acute neurological symptoms:  4 cerebellitis, 2 psychoses, 2 neurocognitive impairment, 2 meningitis. Patients had been on a stable ART for a median of 14 months (10 to 32) and their neurological episode occurred in a context of plasma HIV RNA <500 copies/mL, including 7 with plasma viral load <50 copies/mL.

Results:  Of the total, 3 patients had detectable plasma HIV RNA (78, 147, and 483 copies/mL), but they had had a plasma HIV RNA <50 copies/mL during the previous 6 months. Median count of white cells in cerebrospinal fluid (CSF) was 6 (0 to 76), median protein level was 0.84 g (0.45 to 1.67). All patients had CSF HIV RNA >1 log higher than in plasma, and no other infectious agents. Median CSF HIV RNA was 952 (558 to 12,885) copies/mL. In 7 patients, a genotype analysis performed on HIV strains in the CSF showed significant resistance mutations. The median number of resistance-associated mutations in the CSF HIV RNA was 6.5 (2 to 8) to NRTI, 1.5 (1 to 2) to NNRTI, 3 (2 to 9) to PI. Median CSF score penetration was 2 (1 to 3) and 4 patients had a CSF score penetration of <1.5. Of 9 patients, 8 had MRI images of encephalitis. After treatment modification based on genotypes and drug penetration scores, patients improved clinically, 7 experiencing a CSF control with HIV RNA <200 copies/mL.

Conclusions:  These cases suggest that despite successful suppression of virus in plasma, HIV may replicate independently in some compartments, such as the CNS, which may then result in acute or subacute clinical manifestations. These data support the evaluation of antiretroviral drug efficacy in the CNS in case of any neurological symptoms even if plasma HIV RNA is below limit of quantification.