Cumulative Burden of Depression and All-Cause Mortality in Women Living With Human Immunodeficiency Virus

Mills, Jon C.; Pence, Brian W.; Todd, Jonathan; Bengtson, Angela M.; Breger, Tiffany L; Edmonds, Andrew; Cook, Robert L.; Adedimeji, Adebola; Kassaye, Seble; Milam, Joel; Cocohoba, Jennifer; Cohen, Mardge H.; Golub, Elizabeth T.; Neigh, Gretchen N.; Fischl, Margaret A.; Kempf, Mirjam Colette; Adimora, Adaora A.

doi:10.1093/cid/ciy264

Cited by 35 publications

(15 citation statements)

References 33 publications

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“…Substance use disorders (alcohol, injection drugs and non‐injection drugs) among PLWH are also a growing concern in SSA . While mental health and substance use disorders are associated with suboptimal HIV treatment outcomes, including late ART initiation, poor ART adherence, lack of viral suppression and increased AIDS‐related mortality , the coverage of screening, diagnosis and treatment services for these disorders is extremely limited in SSA . Key constraints include workforce shortages, limited training on mental health and substance use disorders, the lack of validated and culturally appropriate screening and diagnostic tools, as well as the lack of proven treatment interventions that can be integrated into HIV care and delivered by non‐specialists in contexts facing mental health and substance use workforce challenges . Research approaches: The magnitude of mental health and substance use disorders merits further study, along with the effects of integrated treatment for these disorders on HIV outcomes under Treat All .…”

Section: Resultsmentioning

confidence: 99%

Research priorities to inform “Treat All” policy implementation for people living with HIV in sub‐Saharan Africa: a consensus statement from the International epidemiology Databases to Evaluate AIDS (IeDEA)

et al. 2019

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Introduction “Treat All” – the treatment of all people with HIV, irrespective of disease stage or CD4 cell count – represents a paradigm shift in HIV care that has the potential to end AIDS as a public health threat. With accelerating implementation of Treat All in sub‐Saharan Africa (SSA), there is a need for a focused agenda and research to identify and inform strategies for promoting timely uptake of HIV treatment, retention in care, and sustained viral suppression and addressing bottlenecks impeding implementation. Methods The Delphi approach was used to develop consensus around research priorities for Treat All implementation in SSA. Through an iterative process (June 2017 to March 2018), a set of research priorities was collectively formulated and refined by a technical working group and shared for review, deliberation and prioritization by more than 200 researchers, implementation experts, policy/decision‐makers, and HIV community representatives in East, Central, Southern and West Africa. Results and discussion The process resulted in a list of nine research priorities for generating evidence to guide Treat All policies, implementation strategies and monitoring efforts. These priorities highlight the need for increased focus on adolescents, men, and those with mental health and substance use disorders – groups that remain underserved in SSA and for whom more effective testing, linkage and care strategies need to be identified. The priorities also reflect consensus on the need to: (1) generate accurate national and sub‐national estimates of the size of key populations and describe those who remain underserved along the HIV‐care continuum; (2) characterize the timeliness of HIV care and short‐ and long‐term HIV care continuum outcomes, as well as factors influencing timely achievement of these outcomes; (3) estimate the incidence and prevalence of HIV‐drug resistance and regimen switching; and (4) identify cost‐effective and affordable service delivery models and strategies to optimize uptake and minimize gaps, disparities, and losses along the HIV‐care continuum, particularly among underserved populations. Conclusions Reflecting consensus among a broad group of experts, researchers, policy‐ and decision‐makers, PLWH, and other stakeholders, the resulting research priorities highlight important evidence gaps that are relevant for ministries of health, funders, normative bodies and research networks.

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Section: Resultsmentioning

confidence: 99%

Research priorities to inform “Treat All” policy implementation for people living with HIV in sub‐Saharan Africa: a consensus statement from the International epidemiology Databases to Evaluate AIDS (IeDEA)

et al. 2019

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“…Higher frequency of depression has been repeatedly documented in HIV+ compared to HIV-negative (HIV-) subjects: a 2001 meta-analysis found the frequency of MDD to be nearly two times higher in HIV+ subjects (27), with more recent work confirming that figure (1, 28, 29). Beyond the psychological toll of depression in HIV+ subjects, the ramifications extend to its impact on survival, mainly through its effect on treatment adherence (30) and secondary control of the infection: untreated depression was associated with significantly decreased odds of achieving >90% adherence to HAART and significantly lower odds of controlling HIV RNA levels to <500 copies/ml (31).…”

Section: Discussionmentioning

confidence: 97%

Potential Mechanism for HIV-Associated Depression: Upregulation of Serotonin Transporters in SIV-Infected Macaques Detected by 11C-DASB PET

et al. 2019

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Purpose: Increased incidence of depression in HIV+ patients is associated with lower adherence to treatment and increased morbidity/mortality. One possible underlying pathophysiology is serotonergic dysfunction. In this study, we used an animal model of HIV, the SIV-infected macaque, to longitudinally image serotonin transporter (SERT) expression before and after inoculation, using 11C-DASB (SERT ligand) PET imaging. Methods: We infected seven rhesus macaques with a neurovirulent SIV strain and imaged them at baseline and multiple time points after inoculation (group A). Pyrosequencing methylation analysis of the SERT promoter region was performed. We also measured SERT mRNA/protein in brain single-cell suspensions from another group (group B) of SIV-infected animals (n = 13). Results: Despite some animals showing early fluctuations, 86% of our group A animals eventually showed a net increase in midbrain/thalamus binding potential (BP ND ) over the course of their disease (mean increased binding between last time point and baseline = 30.2% and 32.2%, respectively). Repeated-measures mixed-model analysis showed infection duration to be predictive of midbrain BP ND (p = 0.039). Thalamic BP ND was statistically significantly associated with multiple CSF cytokines (P < 0.05). There was higher SERT protein levels in the second group (group B) of SIV-infected animals with SIV encephalitis (SIVE) compared to those without SIVE (p = 0.014). There were no longitudinal changes in SERT gene promoter region percentage methylation between baselines and last time points in group A animals. Conclusion: Upregulated SERT leading to lower synaptic levels of serotonin is a possible mechanism of depression in HIV+ patients, and extrapolating our conclusions from SIV to HIV should be sought using translational human studies.

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“…Prior studies investigating depression and mortality among people with HIV infection have reported increased mortality risk among those with depression diagnoses or questionnaire‐based depressive symptoms , with some exceptions . Some studies focused on multiple mental health and/or substance use disorders , while others investigated joint effects of depression and antiretroviral therapy adherence on mortality .…”

Section: Discussionmentioning

confidence: 99%

Depression and all‐cause mortality risk in HIV‐infected and HIV‐uninfected US veterans: a cohort study

et al. 2019

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Objectives The contribution of depression to mortality in adults with and without HIV infection is unclear. We hypothesized that depression increases mortality risk and that this association is stronger among those with HIV infection. Methods Veterans Aging Cohort Study (VACS) data were analysed from the first clinic visit on or after 1 April 2003 (baseline) to 30 September 2015. Depression definitions were: (1) major depressive disorder defined using International Classification of Diseases, Ninth Revision (ICD‐9) codes; (2) depressive symptoms defined as Patient Health Questionnaire (PHQ)‐9 scores ≥ 10. The outcome was all‐cause mortality. Covariates were demographics, comorbid conditions and health behaviours. Results Among 129 140 eligible participants, 30% had HIV infection, 16% had a major depressive disorder diagnosis, and 24% died over a median follow‐up time of 11 years. The death rate was 25.3 [95% confidence interval (CI) 25.0–25.6] deaths per 1000 person‐years. Major depressive disorder was associated with mortality [hazard ratio (HR) 1.04; 95% CI 1.01, 1.07]. This association was modified by HIV status (interaction P‐value = 0.02). In HIV‐stratified analyses, depression was significantly associated with mortality among HIV‐uninfected veterans but not among those with HIV infection. Among those with PHQ‐9 data (n = 7372), 50% had HIV infection, 22% had PHQ‐9 scores ≥ 10, and 28% died over a median follow‐up time of 12 years. The death rate was 27.3 (95% CI 26.1–28.5) per 1000 person‐years. Depressive symptoms were associated with mortality (HR 1.16; 95% CI 1.04, 1.28). This association was modified by HIV status (interaction P‐value = 0.05). In HIV‐stratified analyses, depressive symptoms were significantly associated with mortality among veterans with HIV infection but not among those without HIV infection. Conclusions Depression was associated with all‐cause mortality. This association was modified by HIV status and method of depression ascertainment.

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Cumulative Burden of Depression and All-Cause Mortality in Women Living With Human Immunodeficiency Virus

Abstract: In this sample of WLWH, increased CDWD elevated mortality rates in a dose-response fashion. More frequent monitoring and enhanced depression treatment protocols designed to reduce CDWD may interrupt the accumulation of mortality risk among WLWH.

Cited by 35 publications

References 33 publications

Research priorities to inform “Treat All” policy implementation for people living with HIV in sub‐Saharan Africa: a consensus statement from the International epidemiology Databases to Evaluate AIDS (IeDEA)

Research priorities to inform “Treat All” policy implementation for people living with HIV in sub‐Saharan Africa: a consensus statement from the International epidemiology Databases to Evaluate AIDS (IeDEA)

Potential Mechanism for HIV-Associated Depression: Upregulation of Serotonin Transporters in SIV-Infected Macaques Detected by 11C-DASB PET

Depression and all‐cause mortality risk in HIV‐infected and HIV‐uninfected US veterans: a cohort study

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