People with history of depression more likely to stop efavirenz due to mental health problems

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HIV-positive patients with a history of depression who receive treatment with the antiretroviral drug efavirenz (Sustiva) are significantly more likely to experience mental health problems during the first four weeks of therapy and to discontinue treatment with the drug than individuals who have not previously been diagnosed with depression, according to a retrospective American study published in the August 1st edition of the Journal of Acquired Immune Deficiency Syndromes. The investigators note that many of the patients stopping efavirenz because of depressive symptoms had well-controlled viral load and argue that although HIV therapy may be virologically “successful” it may be “failing” the patient in other ways.

Efavirenz is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that has been shown to have a potent anti-HIV effect when used in combination with other antiretroviral drugs. Because its efficacy against HIV, its ease of dosing and generally benign side-effect profile, it is often used as a backbone in first-line anti-HIV combinations.

However, efavirenz does cause side-effects, most notably ones affecting the central nervous system and involving symptoms such as dizziness, confusion, forgetfulness, abnormal dreams and difficulty sleeping. These symptoms generally appear soon after treatment with efavirenz has started, but in many patients lessen or go away completely in the ensuing months. More seriously, treatment with efavirenz has been associated with anxiety, depression and suicidal thoughts and actions and in some patients these remain a significant and distressing feature of life whilst taking efavirenz therapy.



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

retrospective study

A type of longitudinal study in which information is collected on what has previously happened to people - for example, by reviewing their medical notes or by interviewing them about past events. 

boosting agent

Booster drugs are used to ‘boost’ the effects of protease inhibitors and some other antiretrovirals. Adding a small dose of a booster drug to an antiretroviral makes the liver break down the primary drug more slowly, which means that it stays in the body for longer times or at higher levels. Without the boosting agent, the prescribed dose of the primary drug would be ineffective.

reverse transcriptase

A retroviral enzyme which converts genetic material from RNA into DNA, an essential step in the lifecycle of HIV. Several classes of anti-HIV drugs interfere with this stage of HIV’s life cycle: nucleoside reverse transcriptase inhibitors and nucleotide reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). 


A precursor to a building block of DNA or RNA. Nucleosides must be chemically changed into nucleotides before they can be used to make DNA or RNA. 

Three doctors offering private HIV care to patients in San Francisco conducted a retrospective chart review to determine the prevalence of depressive symptoms and treatment discontinuation because of neuro-psychiatric problems amongst patients treated with efavirenz during the first four weeks of therapy. Information was also gathered on mental health history in the six months before treatment with efavirenz was started to see if this predicted depressive symptoms whilst taking the drug or treatment discontinuation.

A total of 101 patients, nearly all of whom were gay, were included in the investigators’ analysis. The patients had reasonably well preserved immunological function before starting treatment, the median CD4 cell count being 336 cells/mm3, with median viral load being 25,000 copies/ml.

Half of all the patients had a past history of depression, and 18% of patients with a depressive history discontinued treatment with efavirenz because they experienced neuropsychiatric side-effects. This compared to only 2% of patients with no prior history of depression, a statistically significant difference (p = 0.019).

“Our study revealed an overall incidence of neuropsychiatric symptoms of any kind whilst taking efavirenz-containing regimens of 30%, with a 10% discontinuation rate due to efavirenz-associated neuro-psychiatric side-effects”, write the investigators.

They stress that many patients who discontinued efavirenz because of mental health problems had a good virological response to treatment, their results therefore showing the complex nature of “treatment success.”

A similarly sized, randomised French study reported earlier this year found no significant difference in the overall incidence of depression in people initiating efavirenz-based treatment when compared to a control group taking a boosted protease inhibitor, but did find that people with a history of depression were more likely to experience depressive symptoms after starting treatment with efavirenz.

The investigators recommend that patients with ongoing neuro-psychiatric problems during efavirenz therapy should be switched to treatment with nevirapine or a ritonavir-boosted protease inhibitor. These drugs have not been associated with mental health disorders.

Several limitations of their study are acknowledged by the investigators, not least its retrospective design and the failure to distinguish between different types of depression. They also recognise that their study population almost entirely comprised gay men.


Boly L et al. Depressive symptoms predict increased incidence of neuropsychiatric side-effects in patients treated with efavirenz. J Acquir Immune Defic Syndr 42: 514 – 516, 2006.