High rates of of undocumented efavirenz-related side effects in Uganda

Although CNS side effects associated with efavirenz have led to newer drugs being recommended in in high income countries, WHO guidelines for low and middle income countries still recommend efavirenz for first-line therapy.

This difference in care between rich and poor countries is exagerated by a genetic polymorphism (G516T in CYP P450 2B6) that significantly increases drug levels of efavirenz (by reducing clearance rates) being more common in African compared to Caucasian populations.

Kay Seden from University of Liverpool and colleagues from Makerere University, Uganda, presented results from a prospective, longitudinal observational study to report all side effects in a cohort of 246 Ugandan patients on antiretroviral therapy (ART).

Baseline demographics included mean age 35 years (IQR: 34 to 38), 62% women, median CD4 520 cells/mm3 (329 to 716).

Overall, 134/246 patients were taking an efavirenz-based combination. Of these, 58/134 (43%; 95%CI: 35 to 52%) reported CNS-assocaited side effects (nervous system and/or psychiatric disorders). Severity was self-graded >5/10 by 45 (61%): with 47 (64%), 25 (34%) and 2 (3%) reported as minor, moderate and severe, respectively.

The median duration of side effects was 28 months (IQR 19-42) and only 7% had been reported in medical notes.

In multivariate analysis, risk of side effects was not associated with patient factors such as age, sex, weight or clinical stage.

Comment

The researchers included a comment that many of these paitients might benefit from using the lower 400 mg dose of efavirenz.

Similar side effects in the UK should routinely result in a switch to an alternative combination.

Seden K et al. High prevalence and long duration of nervous system and psychiatric adverse drug reactions in Ugandan patients taking efavirenz 600mg daily. 18th International Workshop on Clinical Pharmacology of Antiviral Therapy. 14-16 June 2017, Chicago. Poster abstract P_55.