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Abstract

Background

Depression is highly prevalent among people living with HIV (PLWH). However, few studies have examined its relationship with clinical and nutritional outcomes in sub-Saharan Africa.

Methods

We conducted a cohort study of 3996 PLWH in Tanzania. Depressive symptoms were measured at antiretroviral therapy (ART) initiation with the Hopkins Symptom Checklist-25 (HSCL-25). Symptoms consistent with depression were defined using the conventional HSCL-25 (score >1.75) and Tanzania-adapted (score >1.06) cutoffs. We evaluated the association of depression defined by both cut-offs and tertiles of HSCL-25 scores with clinical and nutritional outcomes using regression models.

Results

Using the conventional HSCL-25 cutoff, men with symptoms consistent with depression had increased risk of all-cause mortality (hazard ratio (HR): 1.68; 95% CI: 1.17–2.39) and HIV disease progression (HR: 1.59; 95% CI: 1.15-2.19). Women in the highest tertile of depressive symptom scores had increased risk of >10% weight loss (HR: 1.27; 1.05-1.55) and incident pulmonary TB (HR: 1.93, 95% CI: 1.19-3.12).

Conclusions

Depressive symptoms at ART initiation were associated with poor clinical and nutritional outcomes; however, the risks appear to differ by gender and depression severity.

Keywords

HIV depression antiretroviral therapy nutrition tuberculosis mortality

Introduction

Antiretroviral therapy (ART) has led to a dramatic decline in AIDS-related mortality globally.¹ However, morbidity and mortality of people living with HIV (PLWH) initiating ART in sub-Saharan Africa remain higher than those of PLWH in high-income country settings, particularly within the first months of treatment.² PLWH initiating ART in low-income settings have been found to have lower CD4 counts and higher mortality rates compared to their counterparts in high-income settings.² Higher tuberculosis co-infection rates, as well as disproportionate rates of undernutrition and HIV-associated wasting, are also more prevalent.^2,3 As a result, evidence is needed to support interventions that improve survival and treatment outcomes for PLWH during the initial months of ART in sub-Saharan Africa.

The burden of depression is high among PLWH, with PLWH being twice as likely to meet the criteria for major depressive disorder as compared to people who are not living with HIV.⁴ A recent systematic review of the association between depression and clinical outcomes among PLWH found depression to be associated with an increased risk of HIV-associated morbidity and mortality, but most of the evidence was from studies in high-income country settings.^5–9 Evidence from prior studies suggests a link between depression and adverse clinical and nutritional outcomes among PLWH through both behavioral and biological mechanisms.^10–17 Depression may influence immune function through multiple mechanisms, including a reduction in lymphocyte count and dysregulation of serotonin and norepinephrine signaling.¹⁰ Further, non-adherence to antiretroviral medications can result in viral non-suppression as well as the development of drug resistance, thereby increasing the risk of adverse clinical and nutritional outcomes.¹²

Studies of depression among Tanzanian women living with HIV, conducted before the implementation of a test-and-treat ART program strategy, reported that more than half (57%) had symptoms of depression at ART initiation, and depression was associated with an increased risk of mortality and HIV disease progression.¹⁰ Several studies in sub-Saharan Africa have also shown an association between depressive symptoms and low CD4 counts and high HIV viral loads.^7,11,12 However, the relationship of depression with clinical and nutritional outcomes in contemporary HIV cohorts is unclear, as studies have found conflicting results, with multiple indicating that there is no association between depression and mortality and clinical outcomes.^8,13–15 Few studies have investigated the association between depression and clinical outcomes among PLWH in sub-Saharan Africa in test-and-treat ART programs in recent years. Studies have also linked depressive symptoms in PLWH with loss of appetite, undernutrition, and higher TB incidence, but few studies have examined the relationship with nutritional outcomes.^16–19

We conducted a prospective cohort study to examine the association between symptoms consistent with depression and clinical and nutritional outcomes among adult men and women living with HIV and initiating ART in Dar es Salaam, Tanzania. We hypothesized that participants with depression would have an increased risk of death and poor clinical and nutritional outcomes.

Methods

Study Population

We performed a secondary analysis using data from a randomized, double-blind, placebo-controlled trial of vitamin D3 supplementation among 4000 ART-initiating adults with HIV enrolled in Dar es Salaam, Tanzania between February 2015 and March 2018. (ClinicalTrials.gov identifier: NCT01798680).^20,21 The trial protocol and use of secondary data was approved by the Harvard T.H. Chan School of Public Health Institutional Review Board (IRB13-0231), the Tanzanian National Health Research Ethics Sub-Committee (NatHREC) (Ref. No. NIMR/HQ/R.8a/Vol.IX/1658), and the Tanzania Food and Drug Authority (TFDA13/CTR/0005/3). Written and informed consent using Kiswahili forms was obtained from all participants. The protocol and primary results have been reported elsewhere.^20,21 Briefly, participants were required to meet the following inclusion criteria to be eligible for enrollment in the parent trial: (1) adult men or women aged 18 years or older, (2) documented HIV diagnosis, (3) initiation of ART at the time of randomization, (4) low serum 25(OH)D concentration (less than 30 ng/mL) at the screening visit, (5) intent to stay in Dar es Salaam for at least 1 year after enrollment, and (6) provide informed consent. Exclusion criteria included pregnancy or concurrent enrollment in another clinical trial. During the conduct of the trial, the criteria for ART initiation changed from a CD4 T cell count of less than 350 cells/μL or WHO HIV disease stage 3 or 4 to a CD4 T cell count of less than 500 cells/μL in January of 2016.²¹ In June 2016, the program shifted to a test-and-treat strategy, allowing all individuals with HIV to be eligible for ART.²⁰

Data Collection

All participants were administered a questionnaire to collect data on socio-demographic characteristics, alcohol use, and smoking at ART initiation. Weekly clinic visits were conducted for the first three weeks of the trial, and monthly visits from the fourth week until the completion of the trial at 12 months post-ART initiation. At baseline and all follow-up clinic visits, physicians performed a full clinical examination, screened for pulmonary tuberculosis, and assessed WHO HIV disease stage. Participants suspected of having PTB had a chest x-ray and provided sputum samples on three consecutive days. Sputum smears were stained using the Ziehl–Neelsen technique and examined for acid-fast bacilli. PTB was diagnosed when one or more sputum smears had acid-fast bacilli or if there were radiological features suggestive of PTB when smears were negative. Research nurses measured participant height at the baseline visit and assessed participant weight at baseline and all follow-up visits. Participant CD4 T-cell counts were assessed at the ART eligibility visit and every 6 months after ART initiation.

Depression and Social Support Assessment

The depression and social support questionnaires are included in Supplemental Appendix 1. Nurses administered the HSCL-25 (Hopkins Symptom Checklist-25) to measure depressive symptoms at baseline, 6- and 12-months. The HSCL-25, contains 15 depression-related items and 10 anxiety-related items, with participants rating each item on a four-level Likert scale from “not at all” (1) to “extremely” (4).²² The exposure of depression was assessed in three ways: (1) using the standard HSCL-25 cutoff of >1.75 used to screen symptomatic adults,²² (2) using the recalibrated Tanzania-specific cutoff of >1.06 derived from a validation study conducted among pregnant women living with HIV in Dar es Salaam,²³ and (3) a sensitivity analysis using tertiles of total HSCL-25 score within men and women in the study population. A HSCL-25 validation study conducted among pregnant women living with HIV in Dar es Salaam showed an adequate internal consistency (Cronbach's alpha 0.93).²³ In the Tanzania HSCL-25 validation study, the cutoff had 88% sensitivity and 89% specificity using a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis (DSM-IV) of major depressive disorder as the reference.²³ Social support was assessed using the Duke University–University of North Carolina Functional Social Support Questionnaire at ART initiation, 6 months, and 12 months.²⁴ We created instrumental support and emotional support variables based on prior studies in Tanzania.¹⁰ Average scores for these instrumental and emotional support were divided into tertiles.

Statistical Analysis

All analyses were stratified by gender based on a literature review indicating that the prevalence and risks associated with depression may differ between adult men and women.²⁵ We assessed the association of symptoms consistent with depression with mortality, HIV disease progression, incident pulmonary TB disease, change in BMI, and >10% weight loss. The primary analysis was conducted using the Tanzania-specific cutoff (HSCL-25 score > 1.06), and secondary analyses were conducted using the conventional cutoff (HSCL-25 score > 1.75).²⁵ We then conducted exploratory analyses using tertiles of HSCL-25 scores and compared the top tertile for depression score to the lowest two tertiles for depression score. Mortality was defined as deaths from any cause occurring within 1 year of randomization. HIV disease progression was defined as any increase in WHO HIV disease stage or death during follow-up.²⁶ Greater than 10% weight loss from ART initiation at any time in follow-up was selected based on the WHO definition of HIV-related wasting.²⁷

Cox proportional hazard models were used to estimate hazard ratios for the association of depression with the binary outcomes of (i) mortality, (ii) HIV disease progression, (iii) pulmonary TB incidence, and (iv) weight loss >10%. For continuous change in BMI, a linear regression model was used. We presented univariable and multivariable models. Multivariable models included adjustment for age (continuous), marital status (married/cohabitating, single, widowed, divorced/separated), wealth quintile, education (none/primary and secondary or advanced), alcohol use (yes or no), WHO HIV stage (I and II, III, and IV), BMI (<18.5, ≥18.5 and <25, and ≥25.0), CD4 count (≤200, 201-350, 351-500, and >500), pulmonary TB (yes or no), emotional support, instrumental support, and randomized regimen (vitamin D or placebo). The missing indicator method was used to retain participants with missing covariate data in multivariable models. The missing indicator method was used because the covariates with missing data were binary or categorical variables, and this method can account for potential differences between participants with observed and missing covariate data. In a post-hoc power calculation, assuming a 10% event rate and α of 0.05, the study had 80% power to detect hazard ratios ≥1.09 among women and ≥1.13 among men. Analyses were conducted with RStudio using R version 3.6.0.

Results

The parent trial enrolled 4000 participants, and this secondary analysis included 3996 participants (99.9%) with depression data available at ART initiation, with 4 participants being excluded due to missing depression outcome data. Figure 1 presents the participant flow chart and details of participant recruitment and attrition. Sociodemographic and clinical characteristics of the 1264 male and 2732 female participants at ART initiation are presented in Table 1. There were notable differences between men and women at the time of ART initiation, with a higher percentage of men (7.4%) with Stage IV HIV disease compared to women (3.6%). Male participants were also more likely to have CD4-T cell counts ≤ 200 cells/mL compared to women (52.1% as compared to 38.9%, respectively), as well as have pulmonary TB diagnosed at ART initiation (15.4% as compared to 6.1%, respectively). Of the 3996 participants, 413 (10.3%) died within 1 year of ART initiation, and male participants had a greater risk of mortality (15.5%) in comparison to female participants (7.9%).

Figure 1.

Participant flow chart.

Table 1.

Baseline Demographic and Clinical Characteristics at ART Initiation by Gender.

	Men (n = 1264)Mean ± SD or n (%)	Women (n = 2732)Mean ± SD or n (%)
Age (years)	41.5 ± 9.81	37.4 ± 9.6
Marital Status
Married/cohabiting	704 (55.7)	991 (36.3)
Single	244 (19.3)	678 (24.8)
Widowed	58 (4.6)	302 (11.1)
Divorced/separated	232 (18.3)	718 (26.3)
Missing	26 (2.1)	43 (1.6)
Education
None/primary	980 (77.5)	2212 (81.0)
Secondary plus	284 (22.5)	491 (18.0)
Current Smoking
Yes	157 (12.4)	27 (1.0)
No	1107 (87.5)	2705 (99.0)
Current alcohol use
Yes	194 (15.4)	302 (11.1)
No	1070 (84.7)	2430 (89.0)
CD4 T-cell count (cells/mL)
≤ 200	658 (52.1)	1063 (38.9)
201–350	260 (20.6)	639 (23.4)
351–500	137 (10.8)	494 (18.1)
> 500	137 (10.8)	422 (15.5)
Missing	72 (5.7)	114 (4.2)
WHO HIV disease stage
I and II	370 (29.3)	1133 (41.5)
III	801 (63.4)	1500 (54.9)
IV	93 (7.4)	99 (3.6)
Pulmonary TB
Yes	195 (15.4)	167 (6.1)
No	1069 (84.6)	2565 (93.9)
Body mass index (kg/m²)
< 18.5	359 (28.4)	485 (17.8)
≥ 18.5 and < 25.0	755 (59.8)	1343 (49.2)
≥ 25.0	149 (11.8)	903 (33.1)
Mean HSCL-25 depression score (possible range: 25-100)	32.6 ± 10.7	33.6 ± 11.9

Overall, 49.8% of women and 45.4% of men had symptoms consistent with depression using the Tanzanian-adapted cutoff (score >1.06) for depression. The association between the adapted depression cut-off and the clinical outcomes of all-cause mortality, HIV disease progression, weight loss > 10%, pulmonary TB incidence, and continuous BMI is presented in Table 2. For both men and women, there was no statistically significant association between HSCL-adapted depression with clinical and nutritional outcomes in univariable and multivariable models (p-values >0.05).

Table 2.

Association of Depression as Defined by HSCL-Adapted cut-off (>1.06) and Clinical Outcomes Following ART Initiation, Stratified by Gender.

	Women (N = 2732)					Men (N = 1264)
	Events/total (%) orMean ± SD	Univariable HR (95% CI) orMean difference (95% CI)	P value	Multivariate* HR (95% CI) ormean difference (95% CI)	P value	Events/total (%) orMean ± SD	Crude HR (95% CI) orMean difference (95% CI)	P value	Multivariate* HR (95% CI) ormean difference (95% CI)	P value
Mortality
Depression	125/1361 (9.2)	1.40 (1.07−1.83)	0.01	1.24 (0.93−1.66)	0.13	103/574 (17.9)	1.37 (1.04−1.81)	0.03	1.15 (0.85−1.55)	0.36
No depression	91/1371 (6.6)	Ref.		Ref.		94/690 (13.6)	Ref.		Ref.	0.36
HIV disease progression
Depression	231/1361 (17.0)	1.12 (0.93−1.35)	0.23	1.20 (0.98−1.45)	0.07	126/574 (22.0)	1.07 (0.84−1.36)	0.58	1.03 (0.80−1.32)	0.84
No depression	211/1371 (15.4)	Ref.		Ref.		146/690 (21.2)	Ref.		Ref.	0.84
Pulmonary TB
Depression	43/1238 (3.5)	1.64 (1.02−2.63)	0.04	1.58 (0.97−2.58)	0.06	24/537 (4.5)	1.34(0.73−2.48)	0.34	1.17 (0.63−2.18)	0.62
No depression	29/1331 (2.2)	Ref.		Ref.		18/528 (3.4)	Ref.		Ref.	0.62
Weight Loss >10% anytime during follow-up
Depression	150/1240 (12.1)	1.15 (0.92−1.45)	0.22	1.11 (0.87−1.41)	0.40	59/541 (10.9)	0.93 (0.66−1.32)	0.68	0.95 (0.66−1.36)	0.78
No depression	140/1327 (10.6)	Ref.		Ref.		68/579 (11.7)	Ref.		Ref.
Mean BMI change from ART initiation to 1 year of treatment (kg/m²)
Depression	1.77 ± 2.68	0.37 (0.15−0.59)	<0.001	0.19 (−0.02–0.40)	0.08	1.53 ± 2.27	−0.015 (−0.39−0.37)	0.94	−0.24 (−0.61−0.12)	0.20
No depression	1.41 ± 2.55	Ref.		Ref.		1.55 ± 2.80	Ref.		Ref.

*Multivariable models adjusted for baseline age, marital status, wealth quintile, education, alcohol use, WHO HIV stage, BMI, CD4 count, pulmonary TB, and regimen.

Using the conventional HSCL-25 cutoff, 18.2% of women and 14.9% of men were classified as having symptoms consistent with depression. Among females, there was no significant association between depression and clinical and nutritional cutoffs using the conventional cutoff (Table 4). With the conventional cutoff, men with symptoms consistent with depression had 1.68 times the risk (95% CI: 1.17-2.39) of experiencing all-cause mortality compared to those without depression (p-value: 0.004). Men with depression also had 1.59 times the risk (95% CI: 1.15-2.19) of experiencing HIV disease progression as compared to men without depression (p-value: 0.005). Among both men and women, there was no significant difference observed in mean BMI change by depression defined by the conventional cut-off.

We then conducted sensitivity analyses using tertiles of total HSCL-25 score within the population for both men and women. Table 3 presents the association between the highest tertile of HSCL-25 score, as compared to those in the lowest two tertiles, for depression and their clinical outcomes by gender. For both men and women, there was an association between top-tertile depression and increased risk of mortality. Women in the top tertile of HSCL-25 score had an increased risk of pulmonary TB incidence (HR = 1.93, 95% CI: 1.19-3.12) as compared to women in the lower tertiles (p-value: 0.007) (Table 4).

Table 3.

Association of Depression by HSCL-Conventional cut-off (> 1.75) and Clinical Outcomes Following ART Initiation, Stratified by Gender.

		Women (N = 2732)					Men (N = 1264)
	Events/total (%) orMean ± SD	Crude HR (95% CI) orMean difference (95% CI)	P value	Multivariate* HR (95% CI) ormean difference (95% CI)	P value	Events/total (%) orMean ± SD	Crude HR (95% CI) orMean difference (95% CI)	P value	Multivariate* HR (95% CI) or mean difference (95% CI)	P value
Mortality
Depression	48/496 (9.7)	1.31 (0.95−1.80)	0.10	1.16 (0.83−1.62)	0.40	46/188 (24.5)	1.90 (1.37−2.64)	<0.001	1.68 (1.17−2.39)	0.004
No depression	168/2236 (7.5)	Ref.		Ref.		151/1076 (14.0)	Ref.		Ref.
HIV disease progression
Depression	84/496 (16.9)	1.08 (0.85−1.37)	0.52	1.17(0.92−1.50)	0.21	53/188 (28.2)	1.53 (1.14−2.07)	0.005	1.59 (1.15−2.19)	0.005
No depression	358/2236 (16.0)	Ref.		Ref.		219/1096 (20.0)	Ref.		Ref.
Pulmonary TB
Depression	20/441 (4.5)	1.96 (1.17−3.27)	0.01	1.88 (1.11−3.20)	0.02	8/197 (4.1)	1.04 (0.48−2.26)	0.91	0.91 (0.41−1.99)	0.80
No depression	52/2128 (2.4)	Ref.		Ref.		34/868 (3.9)	Ref.		Ref.
Weight Loss >10% anytime during follow-up
Depression	50/432 (11.6)	1.02 (0.76−1.39)	0.88	1.05 (0.77−1.43)	0.77	21/181 (11.6)	1.06 (0.66−1.70)	0.81	1.09 (0.68−1.77)	0.71
No depression	240/2135 (11.2)	Ref.		Ref.		106/939 (11.3)	Ref.		Ref.
Mean BMI change from ART initiation to 1 year of treatment (kg/m²)
Depression	1.77 ± 2.68	0.36 (0.07−0.65)	0.02	0.14 (−0.13–0.42)	0.31	1.53 ± 2.27	−0.01 (−0.54−0.51)	0.96	−0.11 (−0.62−0.40)	0.66
No depression	1.41 ± 2.55	Ref.		Ref.		1.55 ± 2.80	Ref.		Ref.

Multivariable models adjusted for baseline age, marital status, wealth quintile, education, alcohol use, WHO HIV stage, BMI, CD4 count, pulmonary TB, and regimen.

Table 4.

Association of top Tertile of HSCL-25 Score and Clinical Outcomes Following ART Initiation, Stratified by Gender.

	Women (N = 2732)					Men (N = 1264)
	Events/total (%) orMean ± SD	Crude HR (95% CI) orMean difference (95% CI)	P value	Multivariate* HR (95% CI) ormean difference (95% CI)	P value	Events/total (%) orMean ± SD	Crude HR (95% CI) orMean difference (95% CI)	P value	Multivariate* HR (95% CI) ormean difference (95% CI)	P value
Mortality
Top tertile	89/885 (10.1)	1.49 (1.14−1.96)	0.004	1.35 (1.01−1.79)	0.04	83/396 (2.1)	1.67 (1.26−2.22)	<0.001	1.42 (1.04−1.92)	0.03
Lower two tertiles	127/1847 (6.9)	Ref.		Ref.		114/867 (13.1)	Ref.		Ref.
HIV disease progression
Top tertile	155/885 (17.5)	1.15 (0.95−1.40)	0.15	1.28 (1.04−1.57)	0.02	13/336 (3.9)	0.73 (0.36−1.48)	0.03	0.70 (0.34−1.48)	0.06
Lower two tertiles	287/1847 (15.5)	Ref.		Ref.		19/358 (5.3)	Ref.		Ref.
Pulmonary TB
Top tertile	37/905 (4.1)	2.03 (1.28−3.23)	0.003	1.93 (1.19−3.12)	0.007	13/336 (3.9)	0.73 (0.36−1.48)	0.38	0.70(0.34−1.48)	0.35
Lower two tertiles	35/1662 (2.1)	Ref.		Ref.		19/358 (5.3)	Ref.		Ref.
Weight Loss >10% any time during follow-up
Top tertile	181/931 (19.4)	1.23 (1.02−1.48)	0.03	1.27 (1.05−1.55)	0.01	86/424 (20.3)	1.14 (0.87−1.49)	0.33	1.33 (1.00−1.75)	0.05
Lower two tertiles	299/1832 (16.3)	Ref.		Ref.		148/807 (18.3)	Ref.		Ref.
Mean BMI change from ART initiation to 1 year of treatment (kg/m²)
Top tertile	1.66 ± 2.61	0.28 (0.04−0.52)	0.02	0.06 (−0.17–0.29)	0.60	1.61 ± 2.46	0.10 (−0.31–0.51)	0.64	−0.11 (−0.51−0.29)	0.59
Lower two tertiles	1.38 ± 2.55	Ref.		Ref.		1.51 ± 2.83	Ref.		Ref.

Multivariable models adjusted for baseline age, marital status, wealth quintile, education, alcohol use, WHO HIV stage, BMI, CD4 count, pulmonary TB, and regimen.

Discussion

We conducted a prospective cohort study to examine the association between depression and clinical and nutritional outcomes among adults living with HIV initiating HAART in Tanzania. We found no statistically significant association between depression as defined by the Tanzania-adapted cutoff with clinical and nutritional outcomes among men or women. However, using the HSCL-conventional, among men, depression had a greater risk of all-cause mortality and HIV disease progression compared to those without depression. In sensitivity analysis using depressive symptoms score tertiles, women in the top tertile of HSCL-25 score were also at greater risk of incident pulmonary TB, weight loss, HIV progression and mortality compared to women in the lower two tertiles. Differences in the magnitude of the associations by the cutoffs used in our study are important for the interpretation of the findings. The conventional cutoff (HSCL-score > 1.75) is higher than the Tanzania-specific cutoff (HSCL-score > 1.06), and therefore, individuals with depression captured by the conventional cut-off are likely to be of greater severity as compared to those identified by the Tanzania-specific cut-off. The tertile analyses are also suggestive that depression symptom severity can affect the magnitude of the association with clinical and nutritional outcomes. These findings contribute to the growing body of evidence indicating the role of mental health as a critical determinant of physical health in people living with HIV, particularly in sub-Saharan Africa.

We found that symptoms of depression were associated with clinical and nutritional outcomes; however, we noted that the magnitude of the associations differed by the cutoff used to define depression, by gender, and by clinical and nutritional outcome. These findings reinforce that depression is not merely a psychological and emotional concern for PLWH, but also an important predictor of treatment outcomes and a potential area for intervention. Our findings align with previous research that the association differs by gender,^9,11,28,29 which indicates that men diagnosed with HSCL-conventional depression face elevated risks of all-cause mortality and HIV disease progression.^9,11,28,29 One interpretation of these findings is that depressive symptoms disrupt health behaviors, such as ART adherence, engagement in care, and self-care routines.^30,31 Depression has been associated with stress-system dysregulation and increased inflammatory activity, both of which may promote viral replication and faster CD4 cell loss.^4,9 These findings highlight the importance of addressing depression within HIV care frameworks to improve both psychological well-being and clinical outcomes for PLWH.

In terms of nutritional outcomes, we found that women in the highest tertile of depressive symptoms had an increased risk of >10% weight loss from ART initiation; however, there was no association for men. Previous research in sub-Saharan Africa highlights that depression can lead to loss of appetite among PLWH.^32–34 In addition to biological pathways, depression may influence health through appetite, gastrointestinal issues, and disregard for nutritional needs.^32,35 In the context of HIV, where weight loss can signal clinical deterioration, this finding further highlights the interconnectedness of mental and physical health among PLWH. Additionally, the stigma and isolation associated with both HIV and depression may reduce access to social support and food resources, particularly among women.³⁶ These findings suggest that nutritional interventions may be more effective when paired with psychological support. Further research is needed to fully examine the interaction between mental health and nutrition support among men and women living with HIV.

There were several limitations in our study. We did not collect data on ART adherence in our cohort and were therefore not able to assess mediation by treatment adherence. Studies have shown a positive association between symptoms of depression and ART non-adherence in cohorts of PLHIV.^37–39 Furthermore, self-reporting of depressive symptoms introduces the possibility for misclassification due to social desirability and the potential for underestimation of the burden of depression. The exclusion of adolescents and children under 18 years of age in our trial also limits the generalizability of our findings to adults. Additionally, some eligibility criteria for trial entry (eg, low vitamin D levels) may also somewhat affect generalizability. In addition, participants in our study were on efavirenz-based ART regimens and therefore additional research is needed for PLWH newer regimens, including the dolutegravir-based ART. However, pathways related to suboptimal ART adherence and self-care are likely to remain important regardless of the ART regimen. Lastly, because this is an observational study, we are unable to determine any causal effects.

Conclusion

This study underscores the high burden of depressive symptoms, and interventions that integrate mental health care within HIV treatment programs in Tanzania and other similar settings hold promise for improving overall treatment outcomes in PLWH and initiating ART. Our findings also suggest that the effect of interventions to prevent or treat depression may affect clinical and nutritional outcomes differentially for men and women. Future research should explore the efficacy and effectiveness of integrated mental health, ART adherence, and nutritional interventions to support the broader health and well-being of PLWH.

Supplemental Material

sj-docx-1-jia-10.1177_23259582261442282 - Supplemental material for Depressive Symptoms and Clinical and Nutritional Outcomes among Adults Living with HIV Initiating Antiretroviral Therapy in Dar es Salaam, Tanzania

Supplemental material, sj-docx-1-jia-10.1177_23259582261442282 for Depressive Symptoms and Clinical and Nutritional Outcomes among Adults Living with HIV Initiating Antiretroviral Therapy in Dar es Salaam, Tanzania by Kynza Khimani, Alfa Muhihi, Wafaie W. Fawzi, Nzovu Ulenga and Christopher R. Sudfeld in Journal of the International Association of Providers of AIDS Care (JIAPAC)

Supplemental Material

sj-docx-2-jia-10.1177_23259582261442282 - Supplemental material for Depressive Symptoms and Clinical and Nutritional Outcomes among Adults Living with HIV Initiating Antiretroviral Therapy in Dar es Salaam, Tanzania

Supplemental material, sj-docx-2-jia-10.1177_23259582261442282 for Depressive Symptoms and Clinical and Nutritional Outcomes among Adults Living with HIV Initiating Antiretroviral Therapy in Dar es Salaam, Tanzania by Kynza Khimani, Alfa Muhihi, Wafaie W. Fawzi, Nzovu Ulenga and Christopher R. Sudfeld in Journal of the International Association of Providers of AIDS Care (JIAPAC)

Footnotes

Acknowledgements

The authors acknowledge the study participants, whose time, trust, and commitment made this research possible. We also thank the study staff and field teams for their contributions to study implementation and data collection.

ORCID iD

Christopher R. Sudfeld

Ethical Approval and Informed Consent Statements

The study was approved by the Harvard T.H. Chan School of Public Health Institutional Review Board (Ref. No. IRB13-0231), as well as the Tanzanian National Health Research Ethics Sub-Committee (NatHREC) (Ref. No. NIMR/HQ/R.8a/Vol.IX/1658) and the Tanzania Medicine and Medical Devices Authority (TMDA) (Ref. No. TMDA13/CTR/0005/3). All participants provided written informed consent.

Author Contributions

AM, WWF, NU, and CRS contributed to the implementation and data collection in the parent trial. KK and CRS developed the research question and analysis plan. KK conducted the statistical analysis. AM, WWF, NU, and CRS contributed to the implementation of the parent trial. KK wrote the first draft of the manuscript. All authors contributed to the editing and critical revision of the manuscript and approved the final version for submission.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Centers for Disease Control and Prevention, Fogarty International Center, National Institute of Diabetes and Digestive and Kidney Diseases, (grant number NU2GGH002387, NU2GGH002466, D43TW009775, R01DK098075). Nzovu Ulenga’s salary was supported 97% by CDC/PEPFAR funding in 2024/2025 through CoAgs NU2GGH002466 / NU2GGH002387. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funders. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Data Availability Statement

The datasets generated during and/or analyzed during the current study are not publicly available but may be made available from the corresponding author on reasonable request and approval of relevant regulatory bodies.

Supplemental Material

Supplemental material for this article is available online.

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Depressive Symptoms and Clinical and Nutritional Outcomes among Adults Living with HIV Initiating Antiretroviral Therapy in Dar es Salaam,Tanzania

Abstract

Background

Methods

Results

Conclusions

Keywords

Introduction

Methods

Study Population

Data Collection

Depression and Social Support Assessment

Statistical Analysis

Results

Discussion

Conclusion

Supplemental Material

sj-docx-1-jia-10.1177_23259582261442282 - Supplemental material for Depressive Symptoms and Clinical and Nutritional Outcomes among Adults Living with HIV Initiating Antiretroviral Therapy in Dar es Salaam, Tanzania

Supplemental Material

sj-docx-2-jia-10.1177_23259582261442282 - Supplemental material for Depressive Symptoms and Clinical and Nutritional Outcomes among Adults Living with HIV Initiating Antiretroviral Therapy in Dar es Salaam, Tanzania

Footnotes

Acknowledgements

ORCID iD

Ethical Approval and Informed Consent Statements

Author Contributions

Funding

Declaration of Conflicting Interests

Data Availability Statement

Supplemental Material

References