More time with depression increases the risk of death for women with HIV

Increased time living with depression is associated with a higher risk of death for women with HIV, according to US research published in Clinical Infectious Diseases. During five years of follow-up, each 365 days – consecutive or intermittent – with depression increased mortality risk by 72%. A cumulative total of just 90 days with depression had a significant impact on the risk of death from any cause. The impact of cumulative duration of depression on mortality risk was independent of the severity of the most recent episode of depression.

“We found that the more time spent depressed, experienced consecutively or intermittently, increased the hazard of mortality in a dose-response fashion,” comment the authors.

The findings have implications for HIV care, highlighting the importance of the prompt diagnosis and treatment of depression, and of regular monitoring.

Depression is common in people with HIV. Overall prevalence is estimated to be between 20 and 40% and is even higher in women (30 to 60%).

Several studies have shown that depression is associated with increased mortality risk among people with HIV. Depression may increase the risk of death through several pathways including decreased engagement with care, reduced self-care, lack of adherence to antiretroviral treatment or other medication, substance abuse and suicide. Depression may also directly compromise immunity.

Previous research on the link between depression and mortality in people living with HIV has tended to focus on depression as a binary measure, usually always vs never. In reality, in many people depression is chronic and episodic and is therefore likely to have a cumulative effect on mortality over time.

To investigate the impact of cumulative depression, investigators from the Women’s Interagency HIV Study (WIHS) designed a study to determine the cumulative burden of depression among women enrolled in the cohort and its effect on all-cause mortality.

The study population consisted of 818 women who started antiretroviral treatment from 1998 onwards in the WIHS cohort. None of the women were taking antiretroviral therapy at baseline. Using a validated measure (the CESD-R scale), depressive symptoms were assessed at baseline and then at routine six-monthly follow-up appointments for up to five years.

The women had a median age of 38 years at study entry. Two-thirds were black. Median baseline CD4 cell counts and viral loads were 438 cells/mm³ and 3160 copies/ml, respectively.

The women were followed for a median of 4.8 years and contributed a total of 3292 person-years of follow-up. There were 94 deaths, an all-cause mortality rate of 2.9 per 100 person-years. Of the study population, 53% were assessed as ever having depression during the follow-up period.

At the time of last follow-up, the median cumulative number of days with depression (CDWD) was 366 days. CDWD was higher among women who died than women who remained in care to the end of the study (435 vs 355 days).

The authors calculated that each additional 365 days living with depression was associated with a 72% increase in the risk of all-cause mortality (HR = 1.72; 95% CI, 1.34-2.20, p < 0.001).

A cumulative burden of depression of just 91 days also significantly increased mortality risk (HR = 1.14; 95% CI, 1.08-1.22, p < 0.001).

There continued to be a significant association between the total number of days with depression and elevated mortality risk when the investigators took into account the severity of depression at baseline and at the last follow-up visit before death (p = 0.005).

Although much of the study data were collected during a period when antiretroviral treatment was usually deferred until the CD4 cell count had fallen below 350 cells/mm³, and women remained off treatment for the majority of the follow-up period, the investigators say that their results are still relevant to an era when antiretroviral treatment is recommended for all women.

"Our exploratory analysis did not show that receipt of antiretroviral therapy moderates the relationship between depression, [...] consistent with past research using WIHS data."

The investigators say that the findings may not be generalisable to men living with HIV as women have been shown to report a higher level of depressive symptoms than men with HIV in previous research.

The investigators believe their findings have important implications for the routine care of women with HIV.

“Our results highlighting the significance of the durational component of depression have important implications for current practices used in HIV primary care settings,” they write. “At present, HIV treatment guidelines recommend monitoring patients with stable viral loads every six months. However, we found that CDWD less than 182 days increases the risk of mortality. As such, more frequent monitoring of patients with depression in conjunction with integrated depression care protocols designed to shorten the course of depressive episodes could offset further accumulation of mortality risk.”