Depression in People With HIV May Increase Missed Appointments, Detectable Viral Load, and Mortality, Says New Study

Depression has long been recognized not only as a condition that increases risk for acquiring the HIV virus but also as a factor that dramatically impacts the quality of life of and health outcomes for persons living with HIV/AIDS. Researchers have fair agreement on the high occurrence of depression in HIV-positive patients (as high as 40%), but the long-term impact of co-occurring depression and HIV has received little attention. A new study examines the association between increased chronicity of depression in people living with HIV and health outcome indicators, such as HIV appointment attendance, treatment failure, and mortality. The findings reveal both the significant impact of depression and the need for more comprehensive assessment and treatment of depression among people with HIV at various stages in the care continuum.

Depression is the most common neuropsychiatric complication in HIV-positive patients and can occur in all phases of the infection. Many factors are implicated in developing clinical depression in patients with HIV: neurobiological changes related to the persistent viral presence in the central nervous system (CNS), reaction to social stigma and sexual dysfunction, coping with the prospect of illness and death, side effects of antiretroviral therapy, and comorbidities.

The population for this new study came from the Center for AIDS Research Network of Integrated Clinical Systems (CNICS), a collaboration of eight geographically dispersed academic medical centers. Assessment and outcomes data were obtained through the records of nearly six thousand patients receiving care between 2005 and 2015. Standard behavioral health evaluation instruments were utilized: the PHQ-9 to measure depressive symptoms, the Alcohol Use Disorders Identification Test-Clinical for alcohol use, the Alcohol, Smoking, and Substance Involvement Screening Test for substance use, and the AIDS Clinical Trials Group assessment for antiretroviral therapy adherence. Information on mortality was obtained through quarterly site reports and queries of the National Death Index.

Related: Impact of HIV, Age and Comorbidity on Depression and Quality of Life


Other studies have shown that the excess burden of depression among HIV-positive persons in care is about three times greater than that in the general population, and that the likelihood of achieving good antiretroviral adherence is about 40% lower among those with depressive symptoms compared with those without. The new study evaluated depression utilizing a measure of depression-free days, a common metric for mental health trials. Assessment scores were compiled at six-month intervals and sought to examine the negative impact of a longer duration of depression rather than the benefits of anti-depressive treatment.

The specific outcomes utilized were missed HIV primary care appointments, detectable HIV viral load, and all-cause mortality. Appointment data was extracted from administrative records and included all scheduled appointments. Detectable HIV viral load was defined as an HIV RNA viral load of 75 copies/mL or more, and mortality was defined as date of death from any cause. Depression severity measures were converted into "percentage of days with depression" (PDD). The investigators examined whether missed appointments mediated the effect of PDD on viral load, and whether missed appointments and viral load together mediated the effect of PDD on mortality.


On average during follow-up, participants had a median PDD of 14%, with approximately one-third having 0% PDD (no depressive symptoms). Mortality was 1.5 deaths per 100 person-years, the missed appointment rate was 18.8%, and 21.8% had detectable viral loads. Greater PDD was associated in a dose-response fashion with an increased risk of missed appointments, an increased risk of detectable viral load, and accelerated mortality. Each 25% increase in PDD led to an 8% increase in the risk of a missed scheduled appointment, a 5% increase in the risk of detectable viral load, and a 19% increase in mortality hazard. These findings imply that, compared with persons having no depression (PDD of 0%), persons who spent the entire time with depression (PDD of 100%) had a 37% increase in the risk of missed appointments, a 23% increased risk of detectable viral load, and double the mortality hazard. The dose-response assumption held for missed appointments and detectable viral load, but there appeared to be a threshold rather than dose-response relationship for mortality, and persons with all levels of PDD from 25% to 100% had approximately a double hazard of death compared with those having 0% PDD.


This study found that more time spent with depression increased the risk of missed primary care appointments and a detectable viral load, and that even modest increases in time spent with depression (an average of one in four days) doubled the mortality rate.

While many studies have documented the association between HIV and depression, this study extends this work by using a unified analytical approach with three key indicators to measure the impact of depression on people living with HIV across time. There are complex relationships among other comorbidities such as posttraumatic stress disorder, generalized anxiety disorder, and substance misuse, all of which are recognized as barriers to engagement in care and as increasing the risk of mortality. While the association among depression, HIV, and other mental health conditions is complex and bidirectional, this study documents the effect of greater chronicity of depression elevating the risk of missed appointments, detectable viral load, and mortality.

The findings imply that, contrary to the trend of less frequent screening in stable patients, systematic screening and enhanced treatment to shorten the duration of depressive illness may have multiple benefits. Incorporating innovative strategies for care, such as providing depression treatment in non-psychiatric settings, has been shown to be effective in achieving remission of depression. Such integrated, systematic, and ongoing screening of adults living with HIV, as well as the utilization of enhanced treatment protocols in routine HIV care, will have an impact overall HIV health outcomes.

Novel approaches to extend the accessibility of treatment for depression will also be necessary. For example, emerging evidence suggests that trained lay health workers can deliver evidence-based treatments in the absence of mental health professionals. Data also indicate that about 30% of adults with HIV are resistant to standard psychotherapeutic and psychopharmacological treatments for depression, suggesting the need for alternative treatment approaches.

Depression impacts the ability of people living with HIV to effectively manage their health status. The direct correlation among days spent with depression and missed appointments, detectable viral load, and most dramatically, a doubling of mortality, highlights the critical need for integrated and routine screening of all HIV-positive people for depression, as well as strategies to reduce and eliminate the duration of depressive episodes.