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Background: Rates of major depression among people living with HIV (PLWH) are substantially higher than those seen in the general population and this may adversely affect antiretroviral treatment outcomes. Several unique clinical and psychosocial factors may contribute to the development and persistence of depression in PLWH. Given these influences, it is unclear if antidepressant therapy is as effective for PLWH as the general population., Objectives: To assess the efficacy of antidepressant therapy for treatment of depression in PLWH., Search Methods: We searched The Cochrane Common Mental Disorders Group's specialised register (CCMD-CTR), the Cochrane Library, PubMed, Embase and ran a cited reference search on the Web of Science for reports of all included studies. We conducted additional searches of the international trial registers including; ClinicalTrials.gov, World Health Organization Trials Portal (ICTRP), and the HIV and AIDS - Clinical trials register. We searched grey literature and reference lists to identify additional studies and contacted authors to obtain missing data. We applied no restrictions on date, language or publication status to the searches, which included studies conducted between 1 January 1980 and 18 April 2017., Selection Criteria: We included randomized controlled trials of antidepressant drug therapy compared to placebo or another antidepressant drug class. Participants eligible for inclusion had to be aged 18 years and older, from any setting, and have both HIV and depression. Depression was defined according to Diagnostic and Statistical Manual of Mental Disorders or International Statistical Classification of Diseases criteria., Data Collection and Analysis: Two review authors independently applied the inclusion criteria and extracted data. We presented categorical outcomes as risk ratios (RR) with 95% confidence intervals (CIs). Continuous outcomes were presented mean (MD) or standardized mean differences (SMD) with standard deviations (SD). We assessed quality of evidence using the GRADE approach., Main Results: We included 10 studies with 709 participants in this review. Of the 10 studies, eight were conducted in high income countries (USA and Italy), seven were conducted prior to 2000 and seven had predominantly men. Seven studies assessed antidepressants versus placebo, two compared different antidepressant classes and one had three arms comparing two antidepressant classes with placebo.Antidepressant therapy may result in a greater improvement in depression compared to placebo. There was a moderate improvement in depression when assessed with the Hamilton Depression Rating Scale (HAM-D) score as a continuous outcome (SMD 0.59, 95% CI 0.21 to 0.96; participants = 357; studies = 6; I 2 = 62%, low quality evidence). However, there was no evidence of improvement when this was assessed with HAM-D score as a dichotomized outcome (RR 1.10, 95% CI 0.89 to 1.35; participants = 434; studies = 5; I 2 = 0%, low quality evidence) or Clinical Global Impression of Improvement (CGI-I) score (RR 1.28, 95% CI 0.93 to 1.77; participants = 346; studies = 4; I 2 = 29%, low quality evidence). There was little to no difference in the proportion of study dropouts between study arms (RR 1.28, 95% CI 0.91 to 1.80; participants = 306; studies = 4; I 2 = 0%, moderate quality evidence).The methods of reporting adverse events varied substantially between studies, this resulted in very low quality evidence contributing to a pooled estimate (RR 0.88, 95% CI 0.64 to 1.21; participants = 167; studies = 2; I 2 = 34%; very low quality evidence). Based on this, we were unable to determine if there was a difference in the proportion of participants experiencing adverse events in the antidepressant versus placebo arms. However, sexual dysfunction was reported commonly in people receiving selective serotonin reuptake inhibitors (SSRIs). People receiving tricyclic antidepressants (TCAs) frequently reported anticholinergic adverse effects such as dry mouth and constipation. There were no reported grade 3 or 4 adverse events in any study group.There was no evidence of a difference in follow-up CD4 count at study termination (MD -6.31 cells/mm 3 , 95% CI -72.76 to 60.14; participants = 176; studies = 3; I 2 = 0%; low quality evidence). Only one study evaluated quality of life score (MD 3.60, 95% CI -0.38 to 7.58; participants = 87; studies = 1; very low quality evidence), due to the poor quality evidence we could not draw conclusions for this outcome.There were few studies comparing different antidepressant classes. We are uncertain if SSRIs differ from TCAs with regard to improvement in depression as evaluated by HAM-D score (MD -3.20, 95% CI -10.87 to 4.47; participants = 14; studies = 1; very low quality evidence). There was some evidence that mirtazapine resulted in a greater improvement in depression compared to an SSRI (MD 9.00, 95% CI 3.61 to 14.39; participants = 70; studies = 1; low quality evidence); however, this finding was not consistent for all measures of improvement in depression for this comparison.No studies reported on virological suppression or any other HIV specific outcomes.The studies included in this review had an overall unclear or high risk of bias due to under-reporting of study methods, high risk of attrition bias and inadequate sequence generation methods. Heterogeneity between studies and the limited number of participants, and events lead to downgrading of the quality of the evidence for several outcomes., Authors' Conclusions: This review demonstrates that antidepressant therapy may be more beneficial than placebo for the treatment of depression in PLWH. The low quality of the evidence contributing to this assessment and the lack of studies representing PLWH from generalized epidemics in low- to middle-income countries make the relevance of these finding in today's context limited. Future studies that evaluate the effectiveness of antidepressant therapy should be designed and conducted rigorously. Such studies should incorporate evaluation of stepped care models and health system strengthening interventions in the study design. In addition, outcomes related to HIV care and antiretroviral therapy should be reported.

Background: Despite 10 to% of persons living with HIV in sub-Saharan Africa having clinical depression, and the consequences of depression for key public health outcomes (HIV treatment adherence and condom use), depression treatment is rarely integrated into HIV care programs. Task-shifting, protocolized approaches to depression care have been used to overcome severe shortages of mental health specialists in developing countries, but not in sub-Saharan Africa and not with HIV clients. The aims of this trial are to evaluate the implementation outcomes and cost-effectiveness of a task-shifting, protocolized model of antidepressant care for HIV clinics in Uganda., Methods/design: INDEPTH-Uganda is a cluster randomized controlled trial that compares two task-shifting models of depression care--a protocolized model versus a model that relies on the clinical acumen of trained providers to provide depression care in ten public health HIV clinics in Uganda. In addition to data abstracted from routine data collection mechanisms and supervision logs, survey data will be collected from patient and provider longitudinal cohorts; at each site, a random sample of 150 medically stable patients who are depressed according to the PHQ-2 screening will be followed for 12 months, and providers involved in depression care implementation will be followed over 24 months. These data will be used to assess whether the two models differ on implementation outcomes (proportion screened, diagnosed, treated; provider fidelity to model of care), provider adoption of treatment care knowledge and practices, and depression alleviation. A cost-effectiveness analysis will be conducted to compare the relative use of resources by each model., Discussion: If effective and resource-efficient, the task-shifting, protocolized model will provide an approach to building the capacity for sustainable integration of depression treatment in HIV care settings across sub-Saharan Africa and improving key public health outcomes., Trial Registration: INDEPTH-Uganda has been registered with the National Institutes of Health sponsored clinical trials registry (3 February 2013) and has been assigned the identifier NCT02056106.