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Depression, Adherence, and HIV: Untangling the Web


Depression is common among HIV-positive patients, and clearly affects adherence. Treating depression improves adherence, but is also justified in its own right as improperly treated depression can be as devastating as inadequately treated AIDS.

The ability of antiretroviral therapy (ART) to suppress HIV viral replication and reduce transmission depends on nearly perfect adherence to medication regimens.1 However, the average rate of adherence in the United States is about 70%, with about one in 10 patients missing at least one dose on any given day, a third within the past month. In addition, adherence declines over time.2

Depression and other mental health disorders are significant contributors to nonadherence, accounting for a nearly 80% higher rate as well a significant failure to access HIV care and treatment.3 Depression is also significantly more prevalent in an HIV population. A meta-analysis of 10 studies concluded that major depressive disorder was nearly twice as high in HIV-infected individuals as in those without the virus. Rates of diagnosed dysthymia were also nearly two-fold higher.4 Meanwhile, a national survey conducted  in the US identified a 12-month prevalence of depression of 36% compared to the 5-7% prevalence in the general population. 5

Just as depression is linked to worse outcomes in conditions such as cardiovascular disease, so, to, is untreated depression associated with increased morbidity and mortality in HIV-positive patients, even accounting for ART adherence.6-11

However, “just because depression and adherence are associated doesn’t mean that treating the depression will improve the adherence,” said Francine Cournos MD, a professor of clinical psychiatry at Columbia University who treats HIV-infected patients. Instead, she notes, it is important to address both issues: the depression and the nonadherence.

Studies suggest this approach may be effective. A handful of small, randomized, controlled trials have found that using cognitive behavioral therapy to treat moderate to severe depression in HIV-positive patients while also addressing adherence issues can improve both. At least one study also found improved CD4 count over time for the intervention group.12-14

Other studies suggest that treating just the depression may improve adherence. A chart review of 1,713 HIV-positive patients, 57% of whom were diagnosed with depression, found that those who were not receiving antidepressants were less likely to be adherent to ART (P=0.012), with adherence highest among those who were also adherent to antidepressant treatment.15

Another study, involving a cohort of 1,827 female and 3,246 male drug users, found that women with depression  receiving antidepressants and psychiatric therapy were 90% more likely to be adherent to ART treatment than those receiving neither. The improvement was far lower for men, however, at just a 26% improvement. Overall, psychiatric treatment alone was associated with a nearly 50% improved likelihood of adherence.16 

Regardless of the effectiveness of antidepressant treatment on adherence, said Dr. Cournos, it is important that clinicians treat the depression to improve overall outcomes. A recently published study of a long-term follow up of 1,226 older adults diagnosed with depression (but not HIV) found that effective treatment significantly reduced mortality compared to those with depression who did not receive effective interventions.17

Treating depression also appears to improve immune response to ART, regardless of adherence. A community-based prospective cohort study of 158 homeless and marginally housed individuals with HIV and depression, which accounted for depression severity, found those receiving antidepressant treatment were twice as likely to achieve viral suppression and nearly four times as likely to begin ART treatment as those who did not receive antidepressants.18,19

The authors hypothesized that biological pathways that link depression to poorer HIV outcomes, likely related to increased inflammation, as well as behavioral changes, may contribute to the improved physiological outcomes. Indeed, one study found lower levels of HIV-1 RNA in cerebrospinal fluid of 658 HIV-positive patients taking a selective serotonin reuptake inhibitor (SSRI), even those who were not receiving ART.20

Successful approaches for treating depression in HIV populations are similar to those for the general public, namely, antidepressant medication and cognitive behavioral therapy. However, numerous studies also highlight the benefits of other psychosocial interventions, including cognitive behavioral stress management, experiential group psychotherapy, and interpersonal psychotherapy. For certain high-risk populations, such as homeless adults with HIV, directly observed antidepressant therapy may increase effectiveness. 19

“We have to think beyond adherence in terms of why you would treat depression,” said Dr. Cournos. “Depression is more disabling than AIDS. Its impact in undermining functioning is quite profound and worthy of treatment in its own right.”


1.    Thompson MA, Mugavero MJ, Amico KR, et al. Guidelines for improving entry into and retention in care and antiretroviral adherence for persons with HIV: evidence-based recommendations from an International Association of Physicians in AIDS Care panel. Ann Intern Med. 2012;156(11):817-833, W-284, W-285, W-286, W-287, W-288, W-289, W-290, W-291, W-292, W-293, W-294.
2.    Machtinger EL, Bangsberg DR. Adherence to HIV Antiretroviral Therapy. 2005; http://hivinsite.ucsf.edu/InSite?page=kb-03-02-09 - S2X. Accessed January 28, 2014.
3.    Gonzalez JS, Batchelder AW, Psaros C, et al. Depression and HIV/AIDS treatment nonadherence: a review and meta-analysis. J Acquir Immune Defic Syndr. 2011;58(2):181-187.
4.    Ciesla JA, Roberts JE. Meta-analysis of the relationship between HIV infection and risk for depressive disorders. Am J Psychiatry. 2001;158(5):725-730.
5.    Bing EG, Burnam MA, Longshore D, et al. Psychiatric disorders and drug use among human immunodeficiency virus-infected adults in the United States. Arch Gen Psychiatry. 2001;58(8):721-728.
6.    Boarts JM, Sledjeski EM, Bogart LM, et al. The differential impact of PTSD and depression on HIV disease markers and adherence to HAART in people living with HIV. AIDS Behav. 2006;10(3):253-261.
7.    Safren SA, W. Otto M, Worth JL, et al. Two strategies to increase adherence to HIV antiretroviral medication: Life-Steps and medication monitoring. Behav Res Ther. 2001;39(10):1151-1162.
8.    Hartzell JD, Janke IE, Weintrob AC. Impact of depression on HIV outcomes in the HAART era. J Antimicrob Chemother. 2008;62(2):246-255.
9.    Tegger MK, Crane HM, Tapia KA, et al. The effect of mental illness, substance use, and treatment for depression on the initiation of highly active antiretroviral therapy among HIV-infected individuals. Aids Patient Care STDS. 2008;22(3):233-243.
10.    Cook JA, Grey D, Burke J, et al. Depressive symptoms and AIDS-related mortality among a multisite cohort of HIV-positive women. Am J Public Health. 2004;94(7):1133-1140.
11.    Ironson G, O'Cleirigh C, Fletcher MA, et al. Psychosocial factors predict CD4 and viral load change in men and women with human immunodeficiency virus in the era of highly active antiretroviral treatment. Psychosom Med. 2005;67(6):1013-1021.
12.    Safren SA, O'Cleirigh CM, Bullis JR, et al. Cognitive behavioral therapy for adherence and depression (CBT-AD) in HIV-infected injection drug users: a randomized controlled trial. J Consult Clin Psychol. 2012;80(3):404-415.
13.    Simoni JM, Wiebe JS, Sauceda JA, et al. A preliminary RCT of CBT-AD for adherence and depression among HIV-positive Latinos on the U.S.-Mexico border: the Nuevo Dia study. AIDS Behav. 2013;17(8):2816-2829.
14.    Safren SA, O'Cleirigh C, Tan JY, et al. A randomized controlled trial of cognitive behavioral therapy for adherence and depression (CBT-AD) in HIV-infected individuals. Health Psychol. 2009;28(1):1-10.
15.    Yun LW, Maravi M, Kobayashi JS, et al. Antidepressant treatment improves adherence to antiretroviral therapy among depressed HIV-infected patients. J Acquir Immune Defic Syndr. 2005;38(4):432-438.
16.    Turner BJ, Laine C, Cosler L, et al. Relationship of gender, depression, and health care delivery with antiretroviral adherence in HIV-infected drug users. J Gen Intern Med. 2003;18(4):248-257.
17.    Gallo JJ, Morales KH, Bogner HR, et al. Long term effect of depression care management on mortality in older adults: follow-up of cluster randomized clinical trial in primary care. BMJ. 2013;346:f2570.
18.    Tsai AC, Weiser SD, Petersen ML, et al. A marginal structural model to estimate the causal effect of antidepressant medication treatment on viral suppression among homeless and marginally housed persons with HIV. Arch Gen Psychiatry. 2010;67(12):1282-1290.
19.    Tsai AC, Karasic DH, Hammer GP, et al. Directly observed antidepressant medication treatment and HIV outcomes among homeless and marginally housed HIV-positive adults: a randomized controlled trial. Am J Public Health. 2013;103(2):308-315.
20.    Letendre SL, Marquie-Beck J, Ellis RJ, et al. The role of cohort studies in drug development: clinical evidence of antiviral activity of serotonin reuptake inhibitors and HMG-CoA reductase inhibitors in the central nervous system. Journal of Neuroimmune Pharmacology  2007;2(1):120-127.


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