Background
Since its identification in 1981 [
1], HIV infection in the United States has spread from coastal cities to inland rural towns [
2‐
4]. HIV care in rural areas is inferior to HIV care in urban areas: rural patients cite greater obstacles to care, see less experienced HIV providers, and are less likely to receive antiretroviral treatment or prophylaxis against
Pneumocystis jiroveci pneumonia (PCP) than their urban counterparts [
5,
6]. Accordingly, we recently found that rural patients with HIV have higher mortality rates [
7].
Depression is the most common neuropsychiatric complication of HIV disease [
8]. The point prevalence of major depression in HIV infected individuals is 4–10%, with lifetime prevalence estimated between 22–45% [
8]. HIV-infected patients with depression experience poorer physical and social well-being and greater bodily pain. Lastly, HIV patients with depression are less adherent to antiretroviral therapy (ART), and have lower CD4 counts along with an unfavorable general prognosis [
9‐
14].
Given the increasing prevalence of HIV in rural areas, and prior data suggesting that rural patients without HIV infection are at high risk of depression [
15], we examined whether living in rural areas amplifies the risk of depression in HIV-infected patients from New England.
Discussion
In the United States today, rural patients with HIV face greater obstacles to medical care, receive less expert HIV care, experience reduced access to antiretroviral treatment, and have higher mortality rates [
3,
18,
19]. We now show that the prevalence of depression is higher in HIV patients living in rural areas, particularly those on ART. In fact, we observed a gradient of increasing depression moving from metropolitan to micropolitan towns and into small town/rural areas.
The prevalence of depression we observed in rural patients with HIV is higher than rates reported in other populations. Previous studies have cited a prevalence of depression of 5.2% in the general population [
20], 6.1% in rural populations [
15], and a 9.4% in HIV-infected individuals [
20]. While the depression rates in HIV-infected patients in our study cannot be compared directly to these figures, the 59.5% prevalence of depression in HIV patients from small town/rural areas over an 11-year period clearly suggests that these patients are highly vulnerable to this devastating disease.
Further, we found that the prevalence of depression was highest in rural patients on ART. While this finding may recapitulate the prior observation that depression is more common with advanced HIV [
21,
22], it is also possible that the greater vulnerability to depression of rural patients on ART stems from treatment fatigue. Our finding that depression prevalence remains elevated for rural HIV patients across multiple CD4 strata supports this possibility.
HIV-infected rural patients are demographically distinct from HIV patients living in metropolitan areas. Adjusting for these factors in the multivariate model did not impact the clear relationship between living in rural areas and depression. This suggests that demographics alone do not explain the higher depression prevalence in rural HIV patients in New England. Additionally, it newly defines risk factors for depression in this high risk cohort.
We were unable to determine why the prevalence of depression is higher in rural HIV patients. However, we hypothesize that inadequate social support is a major contributor. Two findings support this hypothesis: inadequate social support is linked to higher risk of depression in patients without HIV [
23,
24], and there are fewer social support resources for HIV care in rural areas [
6,
25]. Since patients with HIV are vulnerable to unstable employment [
26], one source for poor social support is limited access to insurance benefits and associated community resources. Furthermore, our clinical experience suggests that support services for HIV care are weak, especially in the small town/rural areas where the prevalence of depression in our patients was the highest. Similarly, because poor social support is known to predict depression in patients on ART [
27], we suspect that inadequate local social support for HIV care may contribute to the extremely high prevalence of depression in rural HIV patients on ART. This is a critical point, because depression undermines ART adherence and is correlated with poorer HIV prognosis [
28‐
30]. Stigma is another major likely contributor to the increasing prevalence of depression in rural areas. Others have shown that rural patients are more likely to encounter AIDS-related stigma [
26], and we posit this may contribute to the great vulnerability to depression we observed in our rural patients.
Our study has important methodological limitations that should be acknowledged. First, the diagnosis of depression in patients in this study was not based on formal criteria; rather, we relied on clinician diagnosis. Thus, provider variability in diagnosis may impact the definition of depression in our study population. However, using this operational definition of depression reflects real world clinical practice [
31], and as such is likely to capture a real burden of psychiatric disease in our study population.
Second, we measured the prevalence of the diagnosis of depression over an eleven year period, not the point prevalence of depression. Therefore, our data are not amenable to survival analysis, and thus bias introduced by differential follow-up between groups is possible. One potential source for differential follow-up is migration. It is conceivable that patients from metropolitan areas left our cohort at a different rate compared to those living in rural areas; however, adjusting for follow-up time in our multivariate model did not undermine the significant relationship between living in rural areas and the prevalence of depression.
Furthermore, we did not characterize the severity of depression or use a rigorous validated screening tool. Thus, our data cannot capture the dynamic incidence or variable severity of the disease, and how this might vary geographically. Lastly, it is possible that individuals in our cohort acquired the diagnosis of depression prior to their HIV diagnosis, and as a result, a substantial proportion of the increased depression prevalence is independent of HIV disease. Nevertheless, it is clinically important that the prevalence of depression in rural HIV patients is much higher than that reported in either rural or HIV populations studied independently.
Importantly, we identified multiple risk factors for depression in HIV patients, including white race and intravenous drug use. However, when controlling for these risk factors in our multivariate analyses, the strong relationship between living in rural areas and the prevalence of depression remained. Therefore, we believe these results are generalizable despite the demographic differences between our rural HIV cohort and those seen in other rural areas of the United States [
3,
18,
32].
We recognize that rurality is a necessarily subjective designation, but believe that the use of validated RUCA scale lends credence to our findings [
16]. Additionally, the fact that we demonstrated a gradient of depression moving from metropolitan cities to micropolitan cities and to small town/rural areas further supports the idea that living in rural areas is an important risk factor for depression in patients with HIV.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
SS performed the statistical analysis, drafted and edited the manuscript, and has given final approval for the manuscript to be published. PJ performed medical chart reviews for data acquisition, revised the manuscript critically, and has given final approval for the manuscript to be published. TL conceived the study, participated in the design and coordination of the study, drafted and edited the manuscript, and has given final approval for the manuscript to be published.