Adverse Neuropsychiatric Events and Recreational Use of Efavirenz and Other HIV-1 Antiretroviral Drugs

Abstract

Efavirenz is a highly effective HIV-1 antiretroviral; however, it is also frequently associated with neuropsychiatric adverse events (NPAE) that include abnormal dreams, sleep disturbances, nervousness, anxiety, depression, and dizziness. The incidence of NPAEs upon initiation of treatment with efavirenz-containing medications is high, exceeding 50% in most studies. Although the NPAEs tend to decrease after the first month in many patients, they persist for long periods of time in others. Efavirenz-based treatment is generally well-tolerated in children, although some experience persistent concentration problems, as well as sleep disturbances, psychotic reactions, and seizures. In an effort to link basic with clinical research, parameters associated with efavirenz brain exposure are discussed, and factors that increase efavirenz levels are explored in depth as they are expected to contribute to NPAE risk. These include the role of modifiable and nonmodifiable risk factors such as diet, weight, and drug-drug interactions and sex, age, and ethnicity/pharmacogenetics. In addition to NPAEs, this review explores what is known about antiretroviral (ARV) drugs being used for recreational purposes. Although multiple ARV drugs are covered, special attention is devoted to efavirenz given that the majority of reports of NPAEs and illicit use of ARV drugs concern efavirenz. The evolving molecular mechanistic basis of NPAEs and abuse of efavirenz point to a complex and polymodal receptor pharmacology. Animal studies to date primarily point to a serotonergic mechanism of action. Recently emerging associations between HIV-associated neurocognitive disorder and efavirenz use, and possible contributions of the mitochondrial-immune-inflammatory-redox cascade are explored in the context of the signaling mechanisms that appear to be involved.

Predictors of Discontinuation of Efavirenz as Treatment for HIV, Due to Neuropsychiatric Side Effects, in a Multi-Ethnic Sample in the United Kingdom

“…18,33 Additionally, research designed to assess the neuropsychiatric effects of different ART regimens and algorithms that predict likelihood of ART discontinuation are required. 34 This study indicates that pre-ART screening for psychological risk factors might be valuable particularly when EFV is being considered given that EFV-free options that induce fewer neuropsychiatric AE are available even in resource-limited settings.…”

Antiretroviral drug use by individuals living with HIV/AIDS and compliance with the Clinical Protocol and Therapy Guidelines

“…(6) In the current study, lamivudine and tenofovir, prescribed as first line HIV therapy, were the most prevalent drugs in the treatment regimens assessed in Paraná. Efavirenz, that ranks next, is associated with neuropsychiatric reactions, (9) but remains as the component of initial treatment for patients with satisfactory results and good tolerance to the drug. (10) It is also indicated preferably as the initial regimen for child-bearing age women.…”

Recreational ART use among individuals living with HIV/AIDS in South Africa: Examining longitudinal ART initiation and viral suppression

“…Efavirenz is a non-nucleoside reverse transcriptase inhibitor which is combined with other antiretroviral medications for use in the treatment of HIV, and it has been prescribed as part of first-line therapy in South Africa since 2013. Efavirenz, like lysergic acid diethylamide (LSD), has activity at the 5HT-2A receptor (Cavalcante et al, 2017;Dalwadi et al, Schetz, 2018;Gatch et al, 2013;Möller et al, 2018). In support of its LSD-like psychoactivity, it has been reported that efavirenz has been smoked in South Africa for its "hallucinogenic and relaxing effect" (Marwaha, 2008).…”