Treating HIV Infection in the Central Nervous System

Abstract

Combination antiretroviral treatment is associated with clear benefits in HIV-positive subjects, and is also effective in the central nervous system (CNS), meaning HIV-associated dementia is now an uncommon event. Nevertheless, a significant number of patients show symptoms of neurocognitive impairment which may negatively affect their quality of life. Although several risk factors for HIV-associated neurocognitive disorders have been identified, there is no clear recommendation for their prevention and management. In this review, the penetration of drugs into the cerebrospinal fluid/CNS is discussed as well as the viral and clinical consequences associated with higher/lower compartmental exposure. We also review the potential interventions according to the currently identified underlying mechanisms, including persistent CNS immune activation, legacy effects, low-level viral replication and escape, co-morbidities, and antiretroviral-associated direct and indirect 'neurotoxicity'. Adjunctive therapies and interventions (including neuro-rehabilitation) are then briefly discussed. The treatment of HIV infection in the CNS is a complex area of therapeutics requiring multidisciplinary interventions and further study.

Central and peripheral reservoirs of feline immunodeficiency virus in cats: a review

“…These findings point to some similarities in viral pathogenesis for the CNS shared by FIV and HIV-1 ( [74,105] -review with references therein). Indeed, based on multiple reports, the brain has proven to be an important target during early FIV infection and, similar to HIV, has been associated with various pathologic features such as encephalitis, microgial activation and, in some cases, degenerative changes like myelin pallor ( [74,105] and references therein; [104,106]). …”

The Glucocorticoid Receptor Is a Critical Regulator of HIV Latency in Human Microglial Cells

“…Much less is known about whether HIV establishes latency in myeloid cells and microglial cells in patients, and whether this has a clinical significance. Nonetheless, it is striking that, even in the era of ART, viral persistence in brain seems to be associated with low basal level of transcriptional expression, giving rise to HAND in 30 to 50% of infected individuals (Heaton et al 2010, 2011, 2015; Chan and Brew 2014; Nightingale et al 2014; Sacktor et al 2016; Calcagno et al 2017). Strong evidence supports the notion that microglia are the only resident cells in the brain parenchyma that can productively be infected with HIV, serving as a viral reservoir in the CNS (Chen et al 2017).…”

Co-morbilidad neuro-psiquiátrica en infección por VIH

“…A pesar de que el diagnóstico de HAND es clínico, se recomienda realizar al menos una neuroimagen y estudio de líquido cefalorraquídeo (LCR), principalmente para descartar la presencia de diagnósticos diferenciales (Tabla 3). Típicamente, un paciente con HAND presentará una neuroimagen normal o bien con alteraciones inespecíficas, El tratamiento consiste, fundamentalmente, en el uso efectivo de TARV, observando el mayor efecto positivo de esta medida en las personas con peor estado neuro-cognitivo basal y mayores cargas virales 4, 20,22,43,45 . En aquellas personas con infección por VIH que ya se encuentran en TARV se ha recomendado el tránsito a fármacos con mejores índices de penetración de la BHE, pero hasta ahora no se ha logrado demostrar un efecto positivo de esta medida 46,47 .…”

“…Respecto a la terapia adyuvante, se han postulado una serie de fármacos para lograr mejorar la función cognitiva en los pacientes con HAND, entre las que se encuentran el uso de rivastigmina, ácido valproico y litio. Lamentablemente, ninguno de ellos ha demostrado generar un cambio significativo en el desempeño de los pacientes 43, 45 . Una medida que sí ha mostrado efectos positivos es el uso de protocolos de rehabilitación, utilizando estrategias como la realización de ejercicios cognitivos 48 .…”