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A growing body of evidence indicates that HIV infection may progress in the brain even when it is controlled in the rest of the body. Researchers compiled a case series of 10 patients in the U.S. and Europe who apparently developed new HIV-related neurological abnormalities despite having optimal virologic control.
At presentation, the patients ranged in age from 26 to 55, had been HIV-infected for a median of 16 years, and had been on stable combination antiretroviral regimens for a median of 21 months. CD4 counts ranged from 290 to 660 cells/mm3, and the median nadir CD4 count was 35 cells/mm3. All 10 patients had viral loads <500 copies/mL (median duration, 28 months), and 5 were suppressed to <50 copies/mL.
Patients presented with a range of motor and sensory problems, including cognitive impairment in seven, ataxia in seven, and coma in one. Analysis of cerebrospinal fluid (CSF) showed pleocytosis or elevated CSF protein levels in all 10 patients. Magnetic resonance imaging (MRI) in eight patients showed white-matter abnormalities in seven; brain biopsy in two showed perivascular lymphocytic infiltrates in the white matter. Evaluations for standard central nervous system (CNS) pathogens, including JC virus, were negative.
HIV RNA levels in the CSF ranged from 134 to 9056 copies/mL. In the five patients with detectable plasma virus, CSF viral loads were at least 1 log higher than plasma viral loads. Genotyping of CSF virus in seven patients showed resistance mutations in all but one; six had mutations associated with nucleoside reverse transcriptase inhibitor resistance, and five had mutations associated with protease inhibitor resistance.
Nine patients were placed on new antiretroviral regimens optimized for CNS penetration and eradication of resistant virus, and eight subsequently showed clinical improvement. All four patients who underwent repeat lumbar puncture had a reduction in CSF HIV RNA. Repeat MRI in two patients showed improvement in one and worsening (despite clinical improvement) in the other.
Peluso MJ et al. Cerebrospinal fluid HIV escape associated with progressive neurologic dysfunction in patients on antiretroviral therapy with well controlled plasma viral load. AIDS 2012 Sep 10; 26:1765.
Comment
Much about this unusual phenomenon of CSF “escape” remains to be confirmed and clarified, but experts agree it is clinically important. Whether it will become more or less common as the duration of effective antiretroviral therapy lengthens in most Western patients remains unclear.