{"id":23992,"date":"2013-12-01T11:31:59","date_gmt":"2013-12-01T11:31:59","guid":{"rendered":"http:\/\/i-base.info\/htb\/?p=23992"},"modified":"2013-12-05T07:37:15","modified_gmt":"2013-12-05T07:37:15","slug":"efavirenz-is-associated-with-higher-suicide-risk-in-meta-analysis-of-four-actg-studies","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/23992","title":{"rendered":"Efavirenz is associated with higher suicide risk in meta-analysis of four ACTG studies"},"content":{"rendered":"

Matt Sharp, HIV i-Base<\/strong><\/p>\n

Efavirenz is one of the most widely used antiretroviral drugs despite a side effect profile that includes anxiety, mood changes, sleep disturbance, depression and serious psychiatric adverse events including suicide ideation and suicide. A new analysis supports these concerns.<\/strong><\/p>\n

In a presentation at IDWeek, Katie Mollan and colleagues analysed retrospective data from four independent investigator-led ACTG trials (A5095, A5142, A5175, A5202) to look for reports of suicidal thinking or behavior from 2001\u20132007. Each ACTG trial was randomised to either efavirenz or a non-efavirenz containing arm (three were PI-based and one was triple nucleoside) in antiretroviral na\u00efve subjects. Three out of four of the trials efavirenz were open label.<\/p>\n

This analysis included 5332 participants (3241 efavirenz, 2091 efavirenz-free) with a median follow-up of 150 weeks. Approximately 74% of participants were enrolled in US sites and 73% were men. The median age was 37 years (IQR 30, 43) and 32% reported a pre-psychiatric diagnosis or were prescribed a psychoactive medication 30 days prior to study entry. Less than 10% had injected drugs.<\/p>\n

In the primary analysis, there were 47 suicide events in the efavirenz arm compared to 15 in the no efavirenz group (8.08 vs 3.66 per 1000 person-years) with a hazard ratio (HR) of 2.28 (95% CI 1.27 to 4.10, p=0.006). Completed or attempted suicide was also higher in the efavirenz group with 17 vs 5 events (2.90 versus 1.22 per 1000 person-years; HR 2.58; 95% CI 0.94 to 7.06, p=0.065), but this was not statistically significant. An intent-to treat analysis showed stronger significance finding 27 vs 7 attempted suicides (HR 2.61; 95% CI:1.1 to 5.9, p=0.03). Similar results were seen in ITT and as treated analyses.<\/p>\n

In multivariate analysis, four risks found to be associated with suicide were use of efavirenz (HR 2.15; 95% CI: 1.20 to 3.87, p=0.01), under 30 years of age versus 45 or older (HR 2.82, 95% CI 1.25 to 6.34, p=0.04), injection drug use history (HR 2.18; 95% CI 1.11 to 4.30, p=0.02) and having a psychiatric history or psychoactive drug use: HR 3.90 (95% CI 2.23 to 6.82, p< 0.001). When assessing for risk in the countries studied, the US was higher (HR 2.32, 95% CI 1.23 to 4.38) compared to other countries (HR 2.02, 95% CI 0.43 to 9.53).<\/p>\n

These results showed that use of efavirenz approximately doubled the risk of suicide with a number needed to harm (NNH) risk over one year of 217 for suicidal thought or behaviour and of 538 for attempted or completed suicide.<\/p>\n

Despite concluding that the overall risk of suicide was low in this analysis, the authors urge that people treated with efavirenz be monitored for suicide risk.<\/p>\n

Comment<\/h3>\n

This is an important analysis given that relatively rare events are unlikely to have statistical significance in smaller studies. This was a large study with three years follow up. The results should prompt a larger analysis from other randomised ACTG studies.<\/strong><\/p>\n

Although suicidal ideation is unlikely to be reported and confounding only allows reporting an association, analyses of suicides and efavirenz use in cohort studies, including D:A:D, might be important given their large patient numbers and length of follow up.<\/strong><\/p>\n

References:<\/p>\n

Mollan K et al. Hazard of suicidality in patients randomly assigned to efavirenz for initial treatment of HIV-1: a cross-study analysis conducted by the AIDS Clinical Trials Group (ACTG). IDWeek 2013. 2-6 October 2013, San Francisco. Abstract 670.
\nhttps:\/\/idsa.confex.com\/idsa\/2013\/webprogram\/Paper40032.html<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

Matt Sharp, HIV i-Base Efavirenz is one of the most widely used antiretroviral drugs despite a side effect profile that includes anxiety, mood changes, sleep disturbance, depression and serious psychiatric adverse events including suicide ideation and suicide. A new analysis …<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[8],"tags":[],"class_list":["post-23992","post","type-post","status-publish","format-standard","hentry","category-side-effects"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/23992","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/comments?post=23992"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/23992\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=23992"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=23992"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=23992"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}