Academic journal article South African Journal of Psychiatry

Efavirenz: A Review of the Epidemiology, Severity and Management of Neuropsychiatric Side-Effects

Academic journal article South African Journal of Psychiatry

Efavirenz: A Review of the Epidemiology, Severity and Management of Neuropsychiatric Side-Effects

Article excerpt

South Africa (SA) has the highest proportion of HIV-positive people in the world. In 2013, an estimated 10% of the population was HIV-positive, which amounted to 5.26 million people. [1] For adults between the ages of 15 and 49 years, an estimated 15.90% were HIV-positive. [1] However, SA has made positive changes in managing the HIV epidemic. The number of people on antiretroviral therapy (ART) has increased, and there have been fewer AIDS-related deaths from 2005 to 2011. [2]

Antiretrovirals used in the management of HIV

HIV cannot be cured; however, there are several major classes of drugs used in its management. The five classes of drugs used for the management of HIV are entry inhibitors, fusion inhibitors, integrase inhibitors, protease inhibitors and reverse transcriptase inhibitors (nucleoside reverse transcriptase inhibitors and non-nucleoside reverse transcriptase inhibitors). [3] These agents act through various mechanisms to stop the replication of HIV. The recommended regimens for the management of HIV in SA are summarised in Table 1. [4]

Efavirenz is a non-nucleoside reverse transcriptase inhibitor that produces its antiretroviral activity by binding directly to the enzyme reverse transcriptase, thus inhibiting replication of the virus. [5] Efavirenz possesses a long half-life of 40-55 hours [6] and is predominantly metabolised in the liver by the CYP450 enzyme system. The specific isoform within the system most important for the metabolism of efavirenz is CYP2B6. [7-9]

Almost 50% of patients on efavirenz experience at least one NPSE. [10-12] In spite of this, efavirenz is part of the first-line regimen of HIV management in SA. The NPSEs tend to occur within the first few days after initiation of therapy and then resolve spontaneously within the first 4-6 weeks. [10] The most commonly reported NPSEs are dizziness, insomnia, headache, abnormal dreams and impaired concentration. [11,13,14] An increased risk of suicidality has been a concern with efavirenz; however, there is conflicting opinion regarding this. [11,12,15] In light of this, patients with an active psychiatric illness being considered for efavirenz therapy should be evaluated in terms of suicide risk, and these patients should be closely monitored after the initiation of therapy.

HIV infection is now regarded as a 'chronic' condition;[16] therefore, it is important to understand the long-term effects of efavirenz. Studies [12,17,18] have been done to assess the long-term effects and have shown that NPSEs may persist for up to 2-3 years following initiation of efavirenz. Dizziness, sleep disturbances, abnormal dreams and light-headedness were the persisting symptoms. [12,17,18] The 2010 Clinical Guidelines for the Management of HIV and AIDS in Adults and Adolescents in South Africa [19] stated that the recommended safety monitoring for the NPSEs of efavirenz is 'clinical'. The term 'clinical' is left open to interpretation with no specific symptoms that should be taken into account when considering a diagnosis being listed. This indicates that it is the responsibility of the clinician to determine whether or not side-effects constitute a clinical change in the patient's condition and what management strategies need to be implemented. These Guidelines also advise that efavirenz should be avoided in patients with untreated depression and patients receiving psychoactive drugs. [19] The 2014 Guidelines [4] warn that efavirenz may cause persistent central nervous system toxicity such as abnormal dreams, depression or mental confusion, and that these side-effects are more likely to occur in patients with current or previous depression or other mental disorder or if the efavirenz is taken during the day. [4] The efavirenz package insert does not state that efavirenz is contraindicated in psychiatric patients. [20] It does, however, mention that efavirenz can cause NPSEs, although the incidence is stated as rare and includes only the following symptoms: anxiety, apathy, emotional lability, euphoria, hallucinations and depression. …

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