Amanor-Boadu S, Hipolito MS, Rai N, McLean CK, Flanagan K, Hamilton FT, Oji V, Lambert SF, Le HN, Kapetanovic S, Nwulia EA. Poor CD4 count is a predictor of untreated depression in human immunodeficiency virus-positive African-Americans. World J Psychiatr 2016; 6(1): 128-135 [PMID: 27014603 DOI: 10.5498/wjp.v6.i1.128]
Corresponding Author of This Article
Evaristus A Nwulia, MD, MHS, Associate Professor of Psychiatry Howard University, Department of Psychiatry and Behavioral Sciences, Translational Neuroscience Laboratory, Howard University, 2041 Georgia Ave., NW, 5th Floor, Washington, DC 20060, United States. enwulia@howard.edu
Research Domain of This Article
Psychiatry
Article-Type of This Article
Retrospective Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Sasraku Amanor-Boadu, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, United States
MariaMananita S Hipolito, Narayan Rai, Charlee K McLean, Evaristus A Nwulia, Department of Psychiatry and Behavioral Sciences, Translational Neuroscience Laboratory, Howard University, Washington, DC 20060, United States
Kyla Flanagan, Flora T Hamilton, Family and Medical Counseling Service, Inc., Washington, DC 20020, United States
Valerie Oji, Lifefountain Center Ministries, Inc., Katy, TX 77450, United States
Sharon F Lambert, Huynh-Nhu Le, Department of Psychology, George Washington University, Washington, DC 20052, United States
Suad Kapetanovic, National Institutes of Health, National Institute of Mental Health, Bethesda, MD 20892, United States
ORCID number: $[AuthorORCIDs]
Author contributions: Amanor-Boadu S and Nwulia EA contributed equally to this work; Hipolito MS, Rai N and McLean CK collected and analyzed the data, and drafted the manuscript; Kapetanovic S and Nwulia EA provided analytical oversight; Nwulia EA designed and supervised the study; Amanor-Boadu S, Kapetanovic S and Nwulia EA revised the manuscript for important intellectual content; Rai N, McLean CK and Flanagan K offered the technical or material support; Hipolito MS, Rai N and McLean CK provided administrative support; all authors have read and approved the final version to be published.
Supported by In whole with Federal funds from the National Cancer Institute, National Institutes of Health, under Contract, No. HHSN261200800001E.
Institutional review board statement: The study was reviewed and approved by the Howard Institutional Review Board.
Informed consent statement: Data collected for the HU IRB approved study has no identifiable information that will link the data to a person.
Conflict-of-interest statement: The content of this publication does not necessarily reflect the views of policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the United States Government.
Data sharing statement: Technical appendix, statistical code and dataset available from the corresponding author at enwulia@howard.edu. Consent was not obtained but the presented data are anonymized and risk of identification is nil.
Open-Access: This is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Evaristus A Nwulia, MD, MHS, Associate Professor of Psychiatry Howard University, Department of Psychiatry and Behavioral Sciences, Translational Neuroscience Laboratory, Howard University, 2041 Georgia Ave., NW, 5th Floor, Washington, DC 20060, United States. enwulia@howard.edu
Telephone: +1-202-8651742 Fax: +1-202-8653068
Received: June 26, 2015 Peer-review started: July 9, 2015 First decision: September 30, 2015 Revised: December 5, 2015 Accepted: December 18, 2015 Article in press: December 21, 2015 Published online: March 22, 2016 Processing time: 264 Days and 4.6 Hours
Abstract
AIM: To determine if efforts to improve antiretroviral therapy (ART) adherence minimizes the negative impact of depression on human immunodeficiency virus (HIV) outcomes.
METHODS: A cross-sectional study of a clinic-based cohort of 158 HIV seropositive (HIV+) African Americans screened for major depressive disorder (MDD) in 2012. CD4 T lymphocyte (CD4+) counts were obtained from these individuals. Self-report on adherence to ART was determined from questionnaire administered during clinic visits. The primary outcome measure was conditional odds of having a poorer CD4+ count (< 350 cells/mm3). Association between CD4+ count and antidepressant-treated or untreated MDD subjects was examined controlling for self-reported adherence and other potential confounders.
RESULTS: Out of 147 individuals with available CD4+ T lymphocyte data, 31% hadCD4+ count < 350 cells/mm3 and 28% reported poor ART adherence. As expected the group with > 350 cells/mm3 CD4+ T lymphocyte endorsed significantly greater ART adherence compared to the group with < 350 cells/mm3 CD4+ T lymphocyte count (P < 0.004). Prevalence of MDD was 39.5% and 66% of individuals with MDD took antidepressants. Poor CD4+ T lymphocyte count was associated with poor ART adherence and MDD. Adjusting for ART adherence, age, sex and education, which were potential confounders, the association between MDD and poor CD4+ T lymphocyte remained significant only in the untreated MDD group.
CONCLUSION: Therefore, CD4+ count could be a clinical marker of untreated depression in HIV+. Also, mental health care may be relevant to primary care of HIV+ patients.
Core tip: A retrospective data review was done on human immunodeficiency virus+ patients of a primary care clinic. We examined data on depression diagnosis of patients over a two-year period. Antiretroviral therapy (ART) adherence and major depressive disorder were associated with CD4+ lymphocyte counts. Non-treatment of depression was associated with poor CD4+ lymphocyte count independent of ART adherence.
Citation: Amanor-Boadu S, Hipolito MS, Rai N, McLean CK, Flanagan K, Hamilton FT, Oji V, Lambert SF, Le HN, Kapetanovic S, Nwulia EA. Poor CD4 count is a predictor of untreated depression in human immunodeficiency virus-positive African-Americans. World J Psychiatr 2016; 6(1): 128-135
Human immunodeficiency virus (HIV) epidemic is a major public health concern, with significant clinical, social and economic impacts, disproportionately affecting minority populations who have less access to care. Approximately 1.2 million people are living with HIV in the United States[1] with 50000 new infections yearly and 1 out of 5 infected people unaware of their status[2]. Since its discovery, HIV/AIDS (acquired immunodeficiency syndrome) has been studied and researched widely and there have been significant improvements in our knowledge of HIV disease and its treatment. The advent of highly active antiretroviral therapy (HAART) has made it possible to suppress the infection, thus prolonging life and putting HIV in the class of chronic long-term infections for many individuals.
Evidence strongly suggests significant association between HIV infection and depression[3]. Prevalence rates of depression are significantly higher in HIV-infected (HIV+) individuals than in the general population[4-7]. The prevalence of depressive symptoms or mood disorders in HIV+ individuals may be about 30% in the United States[4,8]. These prevalence rates vary across specific population groups in HIV+ individuals, with studies reporting higher prevalence rates in HIV+ women than in HIV+ men[3,9,10] and increased depression risk among HIV+ individuals with substance abuse disorders[4,11,12] and among those who have same-sex sexual partners[13,14]. While the prevalence rate of depression decreases with increasing age for the general adult population, this may not be the case for HIV+ adults as evidenced in some studies[15]. Although earlier studies failed to depict this relationship, recent longitudinal studies, especially since the advent of HAART, have observed significant associations between depression and markers of poorer HIV disease outcomes including lower CD4 counts and higher viral loads[16]. The reported associations between depression and HIV disease severity might be mediated by risky behaviors, such as substance abuse, unsafe sexual practices or ART non-adherence, which may further increase transmission risk or exacerbate infection in HIV+ individuals - especially with new drug-resistant viral strains. Indeed, majority of current studies on the subject suggest that co-morbid depression may negatively impact adherence to ART, while non-adherence to HAART, depression and lack of antidepressant use have been associated with accelerated progression of HIV[16-18] and increased mortality[19-21]. On the other hand, given the growing body of scientific evidence implicating important role of immunologic mechanisms in the pathophysiology of major depressive disorder (MDD)[22-24], especially in people with chronic illnesses, it is plausible that the association between MDD and CD4+ outcome could be driven by immunologic mechanisms that are independent from ART adherence and other relevant health behaviors.
This study was conducted with a clinical cohort of African-American HIV+ individuals with or without MDD comorbidity, who reside in a community that has received intense focus and concerted efforts to improve HIV screening, treatment and ART adherence. In an effort to determine if integrating specialized depression management is needed in addition to intense ART adherence promotion, we collected clinical and immunologic data to examine the indirect and direct associations between MDD and CD4+ counts, adjusting for ART adherence. We hypothesized that non-adherence to ART and non-treatment of co-morbid depression would be independently associated with poor CD4+ levels on admission.
MATERIALS AND METHODS
Study site and sample
The study sample consisted of adult HIV+ African Americans who received care at the Family and Medical Counseling Service (FMCS), Inc. during years 2011 and 2012, and who were formally screened for depression during their intake registration. The FMCS, Inc. is a primary care center that provides health services for the largely African American communities living in the South-East zone district of Washington, DC. A blood specimen was collected for each patient at entry, for measurement of viral load, immunologic profiles and other routine tests. All participants completed a detailed biopsychosocial form, comprised of sociodemographic, behavioral, and medical information. All collected data were stored in an encrypted and password-protected electronic medical record (EMR). To search for additional information missing in the EMR, such as names of ART prescribed prior to intake admission and names of abused substances, we reviewed patient paper documents and charts with handwritten notes. This retrospective study was approved by the Howard University Institutional Review Board.
Assessment of depression
As part of their intake registration into the clinic between 2011 and 2012, patients were interviewed with the Substance Abuse and Mental Illness Symptoms Screener (SAMISS), a well-validated 16-item clinician-administered questionnaire that screens for patterns of substance abuse and key psychiatric syndromes, including manic and major depressive episodes, generalized anxiety disorder, panic disorder, post-traumatic stress disorder and adjustment disorder[25]. Additionally, the SAMISS inquires about use of antidepressants in the past year. It is usually administered in 10 min, and has exhibited good psychometric properties[26]. All intake clinical personnel at FMCS were trained to administer the SAMISS in a reliable manner. Patients interviewed with the SAMISS were asked if they had experienced a period lasting two weeks or more in the past year when they felt depressed, and then subsequently asked if they received a diagnosis or treatment(s) for depression. An affirmative response to a two-week period of depression was used for classification of MDD in this study. All patients who screened positive for MDD in the past year either received antidepressants or a physician’s diagnosis of MDD, thereby providing some support to the validity of self-report of MDD in this questionnaire.
Other assessments
CD4+ T lymphocyte counts were measured from blood specimen collected from each patient on the day of clinic intake and during follow-up visits. These results were abstracted from the EMR, were all clinical and laboratory data were stored. We used the most recent CD4+ count for the purpose of this study.
ART adherence and other potential correlates of CD4+ outcome, including age, gender, education, monthly income, housing, and insurance status were derived from the biopsychosocial section of the EMR. As part of their intake interview and during subsequent primary care visits, all patients regardless of their HIV status were asked if they knew about their HIV status, and if they were receiving HIV treatments. Patients who acknowledged being HIV positive were subsequently asked what percentage of time they took their HIV treatments as prescribed by their physicians. For the purpose of this study, we used 80% adherence as threshold for classification of adequacy of ART adherence: ≥ 80% adherence was classified as good or adequate adherence and < 80% was classified as poor or inadequate adherence. Adherence status for subjects who recently became seropositive for HIV was classified as unknown. Substance abuse and pattern of alcohol use were determined from responses to questions in the SAMISS. Problem drinking was defined as heavy drinking (i.e., > 4 drinks per drinking episode) in addition to having experienced difficulty cutting down on drinking or social problems as a consequence of drinking. Additionally, two questions in the SAMISS specifically assessed abuse of prescription and nonprescription drugs in the past year. Presence or absence of substance abuse history was determined from questions in SAMISS inquiring about problem drinking, illicit drug use, and abuse of prescription drugs.
Statistical analysis
The STATA statistical package, version 12 was used to carry out this analysis. The CD4 count data was incomplete with 11 missing values. Since our outcome of interest is CD4 count differences across groups, we excluded subjects with missing information on CD4 count from the regression analyses. We could efficiently do so because the individuals with missing CD4 count values had similar distribution as non-missing across other variables in the data set.
Age, monthly income, and CD4 T lymphocyte count were grouped into categories because of their highly skewed distributions. Age was thus categorized into < 35 years, 35-55 years and > 55 years. Monthly income was grouped into categories according to quartiles. CD4 count was categorized into < 350 cell/mm3 (“poor CD4+ count”) and > 350 cells/mm3 based on earlier findings in studies, that observed that deferring treatment until CD4 count was < 350 cells/mm3 was associated with worse prognosis and mortality[27-29].
χ2 and Fisher’s exact test were used to compare social, demographic and behavioral factors by CD4+ status. For all bivariate analyses, a P value of < 0.05 was regarded as threshold for significance. With the exception of education status and insurance status, missing response rates were less than 8%. Educational status was missing in 33% of individuals and insurance status was missing in 55% of individuals; hence, these latter variables were not included in our multivariate analysis.
We used multiple logistic regression analysis to determine the independent association of MDD with HIV immunological status, adjusting for MDD treatment, ART adherence, age and gender. Several epidemiologic studies have implicated age and gender as key determinants of MDD and HIV outcomes; hence our decision to include these two variables in our multivariate model[30,31]. Ethnicity, another key determinant was not included because our study base consisted of 99% African Americans. The primary outcome measure of interest was the adjusted OR of poor CD4+ outcome comparing MDD treatment groups to nonMDD controls.
RESULTS
Sample characteristics
From October 2011, when depression screening with SAMISS was first implemented in the FMCS, to July 2012, a total of 158 HIV+ patients were enrolled into treatment, and all 158 (100%) of them completed the SAMISS. The 11 individuals who were missing information on CD4+ counts were excluded, resulting in the final sample size of 147. Table 1 depicts the distribution of demographic and behavioral variables by CD4+ count categories among the 147 individuals included in the analysis. As shown, a total of 45 (31%) patients had baseline CD4+ count < 350 cell/mm3. Majority of the patients were males, between 35 and 55 years of age, and with low monthly income; no significant differences for age, sex or monthly income were observed by CD4+ categories. Group differences were, however, observed for education attainment and ART adherence. Twenty-two percent of those with CD4+ count > 350 cells/mm3 received some college education, compared to 42% among those with CD4+ count < 350 cells/mm3 (P < 0.05). However, data on education was missing in 49 patients. As depicted in Table 1, among the patients with CD4 count > 350 cells/mm3, 21% reported poor ART adherence and 50% reported good ART adherence. The ART adherence status of the remaining 29% of patients was classified as “not applicable”, since this group consists of patients with recent HIV+ diagnosis, who have not been prescribed ART. Among the category of patients with poorer CD4+ counts (i.e., < 350 cells/mm3), the proportion with poor adherence is reversed, accounting for 44%. Approximately 24% of patients in the poor CD4 group had untreated depression in the past year, compared to 9% of untreated depression among those with CD4+ count > 350 (Table 1). In addition, 53% of patients in the poor CD4 group had past year MDD diagnosis, compared to 33% past year MDD in those with CD4 count > 350 cells/mm3.
Table 1 Demographic and behavioral characteristics of study participants with and without a CD4 count of < 350 cells/mm3.
Table 2 shows the comparison of ART adherence and other potential demographic and behavioral correlates of poor CD4 outcome between patients with treated MDD, untreated MDD and without MDD. Patients with untreated MDD had the lowest ART adherence rate. No significant differences were observed between these groups in ART adherence. ART adherence was highest among those with treated MDD. Problem drinking rates 55% for the untreated MDD, 46% for treated MDD and 28% for patients without MDD (P < 0.02). No significant differences were observed in age, gender, income, education and substance abuse between the MDD categories.
Table 2 Demographic and behavioral characteristics of study participants with or without depression.
Characteristics
No MDD
MDD treated
MDD untreated
P
(n = 89)
(n = 38)
(n = 20)
(%)
(%)
(%)
Gender
Male
63.27
50
60
0.35
Female
36.73
50
40
Age groups
> 55
24.49
5
15
0.12
35-55
62.24
77.5
70
< 35
13.27
17.5
15
Monthly income
0-200
32.61
30.77
33.33
0.32
204-670
17.39
25.64
5.56
672-739
21.74
30.77
27.78
743-2650
28.26
12.82
33.33
Educational status
No college
70.59
78.57
72.73
0.73
College
29.41
21.43
27.27
Accommodation
Yes
60.42
72.50
70
0.35
No
39.58
27.50
30
HIV treatment adherence
No
26.53
25
45
0.51
Yes
48.98
52.50
40
Unknown
24.49
22.50
15
Substance abuse
No
41.84
30
45
0.37
Yes
58.16
70
55
Problem drinking
No
72.45
53.85
45
0.02
Yes
27.55
46.15
55
Relationship between depression and CD4+ counts
Table 3 depicts the result of our multiple logistic regression analyses for determination of the independent association between MDD and poor CD4+ outcome, adjusting for ART adherence, age and gender. The result of simple logistic regression for each variable in the multiple regression was included to aid comparison of indirect versus direct (i.e., independent) associations. In the un-adjusted analysis (second column of Table 3), the odds of having poor CD4 count in the treated MDD group were 1.68 times that of the non-MDD group, and this difference was not significant (P < 0.3). On the other hand, there was an almost 400% increase in odds of poor CD4 outcome in the untreated MDD group compared to the reference (nonMDD) group (P < 0.008). Adjusting for age, gender and ART adherence, the odds ratio (OR) of poor CD4 comparing untreated MDD to non-MDD patients was 3.12 (P < 0.04).The unadjusted analysis revealed a 60% decreased odds of poor CD4 count outcome comparing the group with good ART adherence to the group with poor ART adherence (P < 0.03). Also in the multivariate analysis, there was a significant inverse association between ART adherence and poor CD4 counts (OR = 0.38, P < 0.03). Our multiple logistic model revealed significant associations between the younger age groups (i.e., < 35 years and 35 to 55 years) and poor CD4 outcome, treating the older age group (i.e., > 55 years) as reference group.
Table 3 Logistic regression analysis of potential risk factors for lower CD4 count of < 350 cells/mm3.
In this study of HIV+ individuals of African-American ethnic background, we found a 39% prevalence of positive screen for depression in the past year, higher than the prevalence rates in the general population and in keeping with previous studies. Untreated depression was associated with lower CD4 T lymphocyte counts, suggesting a significant relationship between untreated depression and immune status in HIV+ individuals. Poorer immunological status was also significantly associated with younger age and non-adherence to ART. These findings are very important as the ultimate result of lower CD4 T lymphocyte counts in HIV disease is progression to AIDS and mortality[32,33].
CD4 T lymphocytes counts are reported as the number of cells in a cubic millimeter of blood. A normal CD4 count is from 500 to 1500 cells per cubic millimeter of blood. CD4 T lymphocytes are primarily targeted by HIV viral cells and play an important role in host immune defenses against opportunistic infections[34]. With progressive HIV disease, CD4 count levels drop to low levels resulting in AIDS defining illness and increasing mortality. As such, CD4 count is one of the most important prognostic markers of HIV-1 disease progression and an important measure in the decision for commencement of ART in HIV+ patients. Our finding of reduced CD4 T lymphocyte count in association with untreated depression has potential clinical significance, as it suggests that CD4 count could potentially be used as clinical marker of untreated co-morbid depression in HIV+ individuals, in addition to its well-established value as marker of HIV disease severity[35].
Efforts to understand the role of the immune system in major depression have been going on for 3 decades. The majority of studies have focused on the role of activated innate immune system in depression, with fewer studies on the role of T lymphocyte cells and other adaptive immune responses[36]. It is of note that some initial studies on T lymphocyte responses in hospitalized depressed patients, revealed a reduced proliferation of T cells in response to T cell mitogens - phytohemagglutinin, concanavalin A[37-39], but these findings were not always reproducible. To elucidate this discrepancy, an extensive metaanalysis of more than 180 studies comprising greater than 40 immune measures, revealed mild reductions in Natural Killer cell count, decreased T cell count and T cell proportions and reduced lymphocyte proliferation responses in depressed patients compared to their controls[40].
The evidence based data depicting T lymphocyte dysfunction in depressed individuals, furthered studies on the role of depression in HIV progression. An extensive literature review on studies carried out in both pre-HAART and post-HAART eras showed depression exacerbates HIV progression to AIDS, with at least three studies further depicting an independent association of depression with decreased CD4 T lymphocyte count in individuals with HIV[32]. An example is a longitudinal study of a multiethnic 177 HIV positive men and women, with CD4 counts of between 150 and 500, followed for 2 years. After adjusting for age, gender, antiretroviral treatment and adherence, cumulative depression and hopelessness were associated with decreases CD4 count and increase in viral load[41].
Our results also show a significant association between ART treatment adherence and CD4+ T lymphocyte count, which is in keeping with previous studies[32,42]. Individuals who were adherent were approximately 60% less likely to have a poor CD4 count in the univariate analysis and after controlling for depression, age and gender. Other studies examining different populations have found depression to be associated with poor ART adherence[41-43]. One of such studies of HIV infected injecting drug users, revealed an association between depression and ART non-adherence as a strong indicator of clinical progression[44]. Another study on indigent low income ethnic minorities with HIV, consisting of mainly African-American population, revealed a significant association between depression and poorer ART adherence[45]. Thus, some studies also discussed the possibility of ART adherence being a potential mediator of sorts in the relationship between MDD and poor CD4+ T lymphocyte outcomes[32,40,41].
In lieu of the mediating effect of ART adherence on the relationship between depression and CD4 count, our study examined if the strength of the relationship between depression and CD4 count diminished by adjusting for ART adherence. Our results confirmed an independent relationship between depression and CD4 count. There was however a 21% decrease in the odds of poorer CD4 count in the untreated depression group after adjusting for ART adherence. Hence, our study shows that ART adherence may be a confounder in the association between untreated depression and poorer CD4 count, especially in light of the fact that nearly 50% of individuals with untreated depression also were non adherent to ART. However, larger prospective studies will be beneficial in further examining the nature of these relationships.
This study has some limitations that should be acknowledged. The cross-sectional design and small sample size limit our ability to make inferences about causal direction of the observed associations and their significance, respectively. The study sample consisted exclusively of African-American individuals from a specific urban community. While this limits the generalizability of the findings, it also provides natural control for potential sociodemographic (e.g., poverty, health disparities) and cultural, racial or community-bound factors that could have confounded the results. It also provides clues that may help inform future clinical and research efforts to adapt evidence based-psychological and social interventions, including mental health screening and treatment monitoring protocols in a manner that will accommodate the sociocultural dimensions of HIV, depression, and salient health behaviors that may be unique to predominantly low-income, African-American urban communities.
In summary, we found that depression is highly prevalent in this population of HIV+ individuals and untreated depression and poor ART adherence are independently associated with poorer CD4 T-lymphocyte outcomes. Furthermore, it contributes to growing appreciation of other possible pathways linking depression to HIV outcome, other than the mediating role of ART adherence. Our findings need to be validated in a larger cohort with follow up over time. There is also a need for further research into the factors that may predispose this community to poorer outcomes. The lower mean income and educational attainment in this clinical cohort also suggests the potential relevance of integrating specialized mental health and case management services into community primary care centers in for better management of HIV+ patients.
ACKNOWLEDGMENTS
This study is not possible without the foresight and support from Drs. Henry Masur and Maryland Pao of the National Institutes of Health. We are also grateful to the staff at the medical records division of the Family Medical Counseling Service, Inc., notably Ms. Deborah Parris, for making the data extraction possible.
COMMENTS
Background
Human immunodeficiency virus (HIV) epidemic is a major public health concern. Approximately 1.2 million people are living with HIV in the United States with 50000 new infections yearly. Evidence strongly suggests significant association between HIV infection and depression. Prevalence rates of depression are significantly higher in HIV-infected individuals in comparison to the general population. The reported associations between depression and HIV disease severity might be mediated by risky behaviors, such as substance abuse, unsafe practices or antiretroviral therapy (ART) non-adherence. Consequently, these factors may further increase transmission risk or exacerbate infection in HIV+ individuals - especially with new drug-resistant viral strains. Recent studies have shown significant association between depression and markers of poorer HIV disease outcomes including lower CD4 counts and higher viral loads. In contrast, the association between major depressive disorder (MDD) and CD4+ outcome could be driven by immunologic mechanisms that are independent from ART adherence. To examine the indirect and direct associations between MDD and CD4+ count, adjusting for ART adherence, the authors collected clinical and immunologic data from the cohort of African-American HIV+ individuals with or without MDD comorbidity. The aim of this study is to see the association between non-adherence to ART and non-treatment of co-morbid depression with poor CD4+ levels on admission.
Research frontiers
Majority of the current studies suggest that co-morbid depression may negatively impact adherence to ART, while non-adherence to highly active ART, depression and lack of antidepressant use have been associated with accelerated progression of HIV and increase mortality. On the other hand, given the growing body of scientific evidence implicating important role of immunologic mechanisms in the pathophysiology of MDD, especially in people with chronic illnesses, it is plausible that the association between MDD and CD4+ outcome could be driven by immunologic mechanisms that are independent from ART adherence and other relevant health behavior.
Innovation and breakthroughs
Efforts to understand the role of the immune system in major depression have been going on for 3 decades. The majority of studies have focused on the role of activated innate immune system in depression, with fewer studies on the role of T lymphocyte cells and other adaptive immune responses. In this study, the authors found 39% prevalence for depression, which is higher than the general population. Untreated depression was associated with lower CD4 T lymphocyte counts, suggesting a significant relationship between untreated depression and immune status in HIV+ individuals. Poorer immunological status was also significantly associated with younger age and non-adherence to ART.
Applications
ART adherence may be a confounder in the association between untreated depression and poorer CD4 count. This study provides the evidence that non-adherence to ART and non-treatment of co-morbid depression would be independently associated with poor CD4+ levels on admission. Practical application: To determine if recent efforts to improve ART adherence among HIV+ African Americans attending a primary care clinic sufficiently minimizes the negative impact of depression on HIV outcomes.
Terminology
Epidemics: Widespread outbreak of infectious disease in a population or community; Cohort: Group of people with common characteristics.
Peer-review
The manuscript explores interesting relationship between CD4 count and depression. It found that there is association between poor CD4 count and untreated depression.
Footnotes
P- Reviewer: Liu-Seifert H, Schweiger U S- Editor: Ji FF L- Editor: A E- Editor: Jiao XK
Centers for Disease Control and Prevention (CDC). HIV surveillance--United States, 1981-2008.MMWR Morb Mortal Wkly Rep. 2011;60:689-693.
[PubMed] [DOI][Cited in This Article: ]
Johnson JG, Rabkin JG, Lipsitz JD, Williams JB, Remien RH. Recurrent major depressive disorder among human immunodeficiency virus (HIV)-positive and HIV-negative intravenous drug users: findings of a 3-year longitudinal study.Compr Psychiatry. 1999;40:31-34.
[PubMed] [DOI][Cited in This Article: ][Cited by in F6Publishing: 1][Reference Citation Analysis (0)]
Moore J, Schuman P, Schoenbaum E, Boland B, Solomon L, Smith D. Severe adverse life events and depressive symptoms among women with, or at risk for, HIV infection in four cities in the United States of America.AIDS. 1999;13:2459-2468.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 106][Cited by in F6Publishing: 100][Article Influence: 4.0][Reference Citation Analysis (0)]
Rabkin JG, Johnson J, Lin SH, Lipsitz JD, Remien RH, Williams JB, Gorman JM. Psychopathology in male and female HIV-positive and negative injecting drug users: longitudinal course over 3 years.AIDS. 1997;11:507-515.
[PubMed] [DOI][Cited in This Article: ]
Levine AJ, Singer EJ, Sinsheimer JS, Hinkin CH, Papp J, Dandekar S, Giovanelli A, Shapshak P. CCL3 genotype and current depression increase risk of HIV-associated dementia.Neurobehav HIV Med. 2009;1:1-7.
[PubMed] [DOI][Cited in This Article: ]
Dubé B, Benton T, Cruess DG, Evans DL. Neuropsychiatric manifestations of HIV infection and AIDS.J Psychiatry Neurosci. 2005;30:237-246.
[PubMed] [DOI][Cited in This Article: ]
Ickovics JR, Hamburger ME, Vlahov D, Schoenbaum EE, Schuman P, Boland RJ, Moore J. Mortality, CD4 cell count decline, and depressive symptoms among HIV-seropositive women: longitudinal analysis from the HIV Epidemiology Research Study.JAMA. 2001;285:1466-1474.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 656][Cited by in F6Publishing: 654][Article Influence: 28.4][Reference Citation Analysis (0)]
Raison CL, Rutherford RE, Woolwine BJ, Shuo C, Schettler P, Drake DF, Haroon E, Miller AH. A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers.JAMA Psychiatry. 2013;70:31-41.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 1037][Cited by in F6Publishing: 1126][Article Influence: 102.4][Reference Citation Analysis (0)]
Palella FJ, Deloria-Knoll M, Chmiel JS, Moorman AC, Wood KC, Greenberg AE, Holmberg SD. Survival benefit of initiating antiretroviral therapy in HIV-infected persons in different CD4+ cell strata.Ann Intern Med. 2003;138:620-626.
[PubMed] [DOI][Cited in This Article: ][Cited by in F6Publishing: 1][Reference Citation Analysis (0)]
Sterne JA, May M, Costagliola D, de Wolf F, Phillips AN, Harris R, Funk MJ, Geskus RB, Gill J, Dabis F. Timing of initiation of antiretroviral therapy in AIDS-free HIV-1-infected patients: a collaborative analysis of 18 HIV cohort studies.Lancet. 2009;373:1352-1363.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 539][Cited by in F6Publishing: 559][Article Influence: 37.3][Reference Citation Analysis (0)]
Kessler RC, Berglund P, Demler O, Jin R, Koretz D, Merikangas KR, Rush AJ, Walters EE, Wang PS. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R).JAMA. 2003;289:3095-3105.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 5389][Cited by in F6Publishing: 5275][Article Influence: 251.2][Reference Citation Analysis (0)]
Levy EM, Borrelli DJ, Mirin SM, Salt P, Knapp PH, Peirce C, Fox BH, Black PH. Biological measures and cellular immunological function in depressed psychiatric inpatients.Psychiatry Res. 1991;36:157-167.
[PubMed] [DOI][Cited in This Article: ]
Ironson G, O’Cleirigh C, Fletcher MA, Laurenceau JP, Balbin E, Klimas N, Schneiderman N, Solomon G. 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;67:1013-1021.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 247][Cited by in F6Publishing: 260][Article Influence: 13.7][Reference Citation Analysis (0)]
Starace F, Ammassari A, Trotta MP, Murri R, De Longis P, Izzo C, Scalzini A, d’Arminio Monforte A, Wu AW, Antinori A. Depression is a risk factor for suboptimal adherence to highly active antiretroviral therapy.J Acquir Immune Defic Syndr. 2002;31 Suppl 3:S136-S139.
[PubMed] [DOI][Cited in This Article: ]
Bouhnik AD, Préau M, Vincent E, Carrieri MP, Gallais H, Lepeu G, Gastaut JA, Moatti JP, Spire B. Depression and clinical progression in HIV-infected drug users treated with highly active antiretroviral therapy.Antivir Ther. 2005;10:53-61.
[PubMed] [DOI][Cited in This Article: ]
