Neurological and Psychiatric Adverse Effects of Antiretroviral Drugs

Abstract

Antiretroviral drugs are associated with a variety of adverse effects on the central and peripheral nervous systems. The frequency and severity of neuropsychiatric adverse events is highly variable, with differences between the antiretroviral classes and amongst the individual drugs in each class. In the developing world, where the nucleoside reverse transcriptase inhibitor (NRTI) stavudine remains a commonly prescribed antiretroviral, peripheral neuropathy is an important complication of treatment. Importantly, this clinical entity is often difficult to distinguish from human immunodeficiency virus (HIV)-induced peripheral neuropathy. Several clinical trials have addressed the efficacy of various agents in the treatment of NRTI-induced neurotoxicity. NRTI-induced neurotoxicity is caused by inhibition of mitochondrial DNA polymerase. This mechanism is also responsible for the mitochondrial myopathy and lactic acidosis that occur with zidovudine. NRTIs, particularly zidovudine and abacavir, may also cause central nervous system (CNS) manifestations, including mania and psychosis. The non-nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz is perhaps the antiretroviral most commonly associated with CNS toxicity, causing insomnia, irritability and vivid dreams. Recent studies have suggested that the risk of developing these adverse effects is increased in patients with various cytochrome P450 2B6 alleles. Protease inhibitors cause perioral paraesthesias and may indirectly increase the relative risk of stroke by promoting atherogenesis. HIV integrase inhibitors, C-C chemokine receptor type 5 (CCR5) inhibitors and fusion inhibitors rarely cause neuropsychiatric manifestations.

Over Exposure to Efavirenz Plasma Concentrations among Beninese HIV Patients Treated by A 600 mg Daily Dose

“…In the same way, Vrouenraets et al [22] did not report these affections. In contrast, it has been reported cases of patients suffering from depression (17%) and delirium (13%) in other study [23]. Absence of identification of certain psychiatric AE in our study can be related to skews of questionnaire used during the data-gathering.…”

Efavirenz Induces Neuronal Autophagy and Mitochondrial Alterations

“…Efavirenz (EFV) is the most widely used NNRTI and is recommended for use in treatment-naïve patients. EFV is generally well tolerated but does cause significant CNS side effects, including insomnia, confusion, agitation, amnesia, euphoria, and vivid dreams (Abers et al, 2014). Adverse CNS effects interfere with patient adherence and cause EFV intolerance; however, the etiology of this effect is not understood.…”

Leucopatía reversible de la protuberancia: en paciente con SIDA y tratamiento retroviral

“…Esto basado en la imposibilidad clínica de una desmielinización central de la protuberancia en un paciente que nunca presentó alteraciones motoras. Se pensó en la especial capacidad que tendrían las terapias retrovirales para generar estrés oxidativo o efectos neurotóxicos, que en este caso pudieran haber comprometido la funcionalidad de las neuronas propias del puente, desarrollando alteraciones mitocondriales, así como cambios en la permeabilidad de la barrera hematoencefálica local, debido a los efectos citotóxicos producido por el tratamiento 14 . Sin embargo, el silencio neuroló-gico, el antecedente de una terapia antirretroviral tóxica, su vinculación a imágenes patológicas en la RM y su condición reversible, hicieron surgir como alternativa diagnóstica la leucoencefalopatía posterior reversible, síndrome ampliamente reconocido 2 , donde la experiencia ha demostrado quelas imágenes que acompañan o definen la LPR no están limitadas a regiones occipitoparietales ("posteriores"), sino que pueden expresarse mucho más extensamente 15,16 o aparecer aisladamente en un punto del SNC como la protuberancia 17 .…”

“…La LPR ha estado comúnmente vinculada con medicamentos que producen efectos sobre la barrera hematoencefálica, condición generalmente idiosincrática, por ello esta leucopatía reversible de la protuberancia podría ser compatible con una terapia antirretroviral, tóxica para este enfermo 14 .…”