HIV encephalitis related to the development of a discordant resistant virus in CNS

Abstract

The central nervous system (CNS) is considered to be one of the sanctuary sites for human immunodeficiency virus (HIV). HIV replication in the CNS can take an independent course that leads to the appearance of HIV quasi-species with different resistance profiles [1]. On the other hand, the blood–brain barrier hinders the delivery of antiretroviral drugs to the parenchyma. Antiretroviral therapy (ART) should thus reach appropriate levels in CNS. In order to establish this, after analysis of distributions of antiretroviral drugs into the CNS, a CNS penetration effectiveness (CPE) score was proposed in 2008 and reviewed in 2010 [2]. Higher CPE scores correlate with lower central cerebrospinal fluid (CSF) viraemia; a CPE greater than 6 is thus recommended to achieve control of HIV replication in the CNS [2]. However, patients with undetectable plasma virus load may experience HIV encephalitis. A 45-year-old white man presented with excessive sleepiness and seizures of 3 months’ duration. Ten years before, the patient had been diagnosed with acquired immunodeficiency syndrome by a wild-type HIV-1 genotype, with a CD4 nadir of 45 cells/mL. Therapy with lopinavir/ritonavir, abacavir and lamivudine (CPE 8) had been initiated; virus load had been kept under control (<20 copies/mL) over follow-up, with occasional blips, and CD4 count was 700 cells/mL. At admission, he was afebrile, with normal blood pressure, and neurologic examination revealed drowsiness, confusion and bilateral Babinski sign. During the first 24 hours, he manifested generalized tonicclonic seizures without recovering consciousness.