Use of Truvada PrEP Not Linked to Depression in iPrEx Analysis

Although depression-related symptoms were the most common severe adverse events in the iPrEx trial of HIV pre-exposure prophylaxis (PrEP) among men who have sex with men, there was no association between depression and use of Truvada (tenofovir/emtricitabine) compared to placebo, according to a report in the June 16 edition of AIDS and Behavior.

Patricia Defechereux and Robert Grant from the Gladstone Institutes and fellow investigators with the iPrEx Study Team conducted a longitudinal and cross-sectional analysis of depressive symptoms among iPrEx participants.

As previously reported, iPrEx was an international study in which 2499 men who have sex with men and a small number of transgender women were randomly assigned to receive oral Truvada or placebo once-daily. Participants taking Truvada had a 44% lower risk of HIV infection overall, rising to 92% among those with blood drug levels indicating good adherence. Truvada was generally safe and well-tolerated.

Depression-related events were the most frequently reported severe or life-threatening adverse events, but they were not significantly associated with being randomized to receive Truvada rather than placebo (152 vs 144 cases, respectively; odds ratio 0.66). Response to the standardized Center for Epidemiologic Studies Depression scale (CES-D) and a 4-questions suicidal ideation scale did not differ by treatment arm. However, depression scores were higher among participants who said they were forced to have anal sex the first time and among those reporting receptive anal intercourse without condoms.

"We recommend continuing PrEP during periods of depression in conjunction with provision of mental health services," the study authors concluded.

Below is an edited excerpt from a Gladstone Institutes press release describing the study findings in more detail.

PrEP Is Not Linked to Greater Risk for Depression

June 18, 2015 -- A new paper out of the iPrEx study -- a randomized, placebo-controlled trial of daily oral HIV pre-exposure prophylaxis (PrEP) in men and transgender women who have sex with men -- reported no link between taking Truvada for oral PrEP and experiencing depression.

During the iPrEx study, depression was the most frequently reported adverse event. As the use of Truvada for HIV prevention increases, it is important to understand the impact of PrEP on depression and whether depression can hinder PrEP.

"We've shown Truvada to be safe and effective for HIV prevention," says senior author Robert Grant, MD, MPH, a senior investigator at the Gladstone Institutes. "Because previous studies suggested a link between certain antiretroviral therapies and depression, we wanted to explore whether or not there was an increased risk for psychosocial health problems associated with PrEP."

The current study, published in AIDS and Behavior, systematically examined whether there was a causative link between Truvada and depression. Comparing scores on a depression and a suicidal ideation scale administered during the study, the researchers found there was no difference in depression or suicidality between participants who received Truvada or placebo. There was also no difference in the number of depression-related adverse events between the two study groups. In addition, there was no evidence that PrEP was less efficacious in depressed participants.

However, half of all participants in the iPrEx study, regardless of the study arm they were in, reported depression scores over the threshold for clinically significant depression. It is well documented that rates of depression are substantially higher among gay men and transgender women who have sex with men.

"Depressive symptoms are associated with sexual practices that increase risk for HIV acquisition," said first author Patricia Defechereux, PhD, a senior research associate at the Gladstone Institutes. "The additional protection conferred by PrEP during episodes of depression could avert infections during these especially vulnerable times."

Scientists from the University of California, San Francisco, Fenway Community Health, Investigaciones Medicas en Salud, University of Michigan, Desmund Tutu HIV Foundation, Fundacion Ecuatoriana Equidad, University of Sao Paulo, and National Institutes of Health also took part in this research. Funding was provided by the Division of Acquired Immunodeficiency Diseases, National Institutes of Health, and the Bill and Melinda Gates Foundation. Study drugs were donated by Gilead Sciences.

6/26/15

Reference

PA Defechereux, M Mehrotra, AY Liu, RM Grant, et al. Depression and Oral FTC/TDF Pre-exposure Prophylaxis (PrEP) Among Men and Transgender Women Who Have Sex With Men (MSM/TGW). AIDS and Behavior. June 16, 2015 (Epub ahead of print).

Other Source

Gladstone Institutes. PrEP Is Not Linked to Greater Risk for Depression. Press release. June 18, 2015.