Efavirenz does not increase the risk of suicidal thoughts or depression in Ugandan adults

Treatment with the antiretroviral drug efavirenz did not increase the risk of depressive symptoms or suicidal thoughts in adults living with HIV in Uganda when compared to nevirapine-based treatment, a prospective cohort study published in Annals of Internal Medicine reports.

Indeed, the study found that adults taking efavirenz were significantly less likely to have signs of depression.

The non-nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz is one of the most widely prescribed antiretroviral drugs in the world and is recommended for use in first-line treatment in lower-income countries by the World Health Organization.



A mental health problem causing long-lasting low mood that interferes with everyday life.

person years

In a study “100 person years of follow-up” could mean that information was collected on 100 people for one year, or on 50 people for two years each, or on ten people over ten years. In practice, each person’s duration of follow-up is likely to be different.

not significant

Usually means ‘not statistically significant’, meaning that the observed difference between two or more figures could have arisen by chance. 

central nervous system (CNS)

The brain and spinal cord. CNS side-effects refer to mood changes, anxiety, dizzyness, sleep disturbance, impact on mental health, etc.

first-line therapy

The regimen used when starting treatment for the first time.

An analysis of AIDS Clinical Trials Group studies found an increased risk of suicidality in people who received efavirenz but a systematic review of 42 randomised trials failed to find an association. Depression is a side-effect of efavirenz treatment in a minority of patients but its frequency has not been established in people receiving the drug in sub-Saharan Africa.

To answer this question, researchers looked at data from the Uganda AIDS Rural Treatment Outcomes cohort study, which followed 694 people who received antiretroviral treatment between 2005 and 2015. Participants contributed 1200 person-years of follow-up, 460 person-years of this follow-up in people receiving efavirenz.

The study population had a median age of 32 years at baseline, just under two-thirds of efavirenz recipients and three-quarters of nevirapine recipients were women, and the majority of people took efavirenz with either tenofovir and lamivudine (172) or zidovudine and lamivudine (117).

One-third of participants were assessed as having possible depression at enrolment and just under 7% reported suicidal thoughts.

Study participants in both arms were followed for a median of 96 weeks and had a median of six follow-up visits (seven in nevirapine recipients). Loss to follow-up was more frequent in the nevirapine recipients (10.3% vs 4.3%, p < 0.001)

During the follow-up period, probable depression was observed more frequently in nevirapine recipients than efavirenz recipients (adjusted risk for outcome 9.7 cases per 100 person-years vs 6.6 cases). Using a Cox proportional hazard regression model, efavirenz treatment was associated with a 44% reduction in the risk of depression compared to nevirapine treatment (aHR 0.56, 95% CI 0.35-0.89, p = 0.013).

Suicidal thoughts did not occur more frequently in efavirenz recipients (3.1 first reports in efavirenz recipients vs 7.4 reports per 100 person-years of follow-up in nevirapine recipients, a non-significant risk difference).

The study investigators found that the relationship between efavirenz and a reduced risk of depression persisted in sub-group analyses.

The authors suggest that slower metabolic processing of efavirenz resulting in lower peak levels of the drug and less central nervous system toxicity, observed in some African populations, might explain the result. They also point out that previous studies finding a higher frequency of suicidal thoughts in efavirenz recipients largely compared the drug with protease inhibitor-based treatment, not NNRTI-based treatment.


Chang JL et al. Depression and suicidal ideation among HIV-infected adults receiving efavirenz versus nevirapine in Uganda. Annals of Internal Medicine, advance online publication, http://doi:10.7326/M17-2252