HIV-related stigma, depression, and social support are associated with health-related quality of life among patients newly entering HIV care.

Entering HIV care is a vulnerable time for newly diagnosed individuals often exacerbating psychosocial difficulties, which may contribute to poor health-related quality of life (HRQOL) ultimately influencing health behaviors including ART adherence, the driver of viral load suppression. Understanding HRQOL in people newly entering HIV care is critical and has the potential to guide practice and research. This exploratory cross-sectional study examined demographic, clinical, and psychosocial factors associated with limitations in four specific domains of HRQOL among persons initially entering outpatient HIV care at four sites in the United States (n = 335). In the unadjusted analysis, female gender was significantly associated with sub-optimal HRQOL with women having increased odds of reporting HRQOL challenges with pain, mood, mobility, and usual activity when compared to men. The adjusted models demonstrated attenuation of parameter estimates and loss of statistical significance for the associations with impaired HRQOL observed among women in unadjusted analyses, suggesting psychosocial factors related to HRQOL are complex and interrelated. Findings are consistent with a robust literature documenting gender-related health disparities. Programs aimed at improving HRQOL for persons initially entering HIV care are warranted generally, and specifically for women, and must address modifiable psychosocial factors via mechanisms including coping and social support.

HIV Standard of Care for ART Adherence and Retention in Care Among HIV Medical Care Providers Across Four CNICS Clinics in the US.

Despite the issuance of evidence-based and evidence-informed guidelines to improve engagement in HIV care and adherence-related outcomes, few studies have assessed contemporary adherence or engagement support practices of HIV care providers in US clinics. As a result, the standard of HIV care in the US and globally remains poorly understood. This programmatic assessment approach aimed to identify the strengths and gaps in the current standard of HIV care from the perspective of HIV care providers. A self-administered Standard of Care measure was developed and delivered through Qualtrics to HIV care providers at four different HIV care sites as a part of a multisite intervention study to improve engagement in HIV care and ART adherence. Providers were asked to provide demographic and clinic specific information, identify practices/strategies applied during typical initial visits with HIV-positive patients and visits prior to and at ART initiation, as well as their perceptions of patient behaviors and adequacy of HIV care services at their clinics. Of the 75 surveys which were completed, the majority of respondents were physicians, and on average, providers have worked in HIV care for 13.5 years. Across the sites, 91% of the providers' patient panels consist of HIV-positive patients, the majority of whom are virally suppressed and 1/5 are considered "out of care." Few resources were routinely available to providers by other staff related to monitoring patient adherence and engagement in care. During typical initial visits with HIV positive patients, the majority of providers report discussing topics focused on behavioral/life contexts such as sexual partnerships, sexual orientation, disclosure, and other sources of social support. Nearly all providers emphasize the importance of adherence to treatment recommendations and nearly 90% discuss outcomes of good adherence and managing common side effects during ART start visits. Overall, providers do not report often implementing practices to improve retention in care. Survey results point to opportunities to enhance engagement in HIV care and improve ART adherence through systematic data monitoring and increased collaboration across providers and other clinic staff, specifically when identifying patients defined as "in need" or "out of care." Trial Registration: Clinicaltrials.gov NCT01900236.

The Depression Treatment Cascade: Disparities by Alcohol Use, Drug Use, and Panic Symptoms Among Patients in Routine HIV Care in the United States.

Little is known about disparities in depression prevalence, treatment, and remission by psychiatric comorbidities and substance use among persons living with HIV (PLWH). We conducted a cross-sectional analysis in a large cohort of PLWH in routine care and analyzed conditional probabilities of having an indication for depression treatment, receiving treatment, receiving indicated treatment adjustments, and achieving remission, stratified by alcohol use, illicit drug use, and panic symptoms. Overall, 34.7% (95% CI 33.9-35.5%) of participants had an indication for depression treatment and of these, 55.3% (53.8-56.8%) were receiving antidepressants. Among patients receiving antidepressants, 33.0% (31.1-34.9%) had evidence of remitted depression. In a subsample of sites with antidepressant dosage data, only 8.8% (6.7-11.5%) of patients received an indicated treatment adjustment. Current drug users (45.8%, 95% CI 43.6-48.1%) and patients reporting full symptoms of panic disorder (75.0%, 95% CI 72.9-77.1%) were most likely to have an indication for antidepressant treatment, least likely to receive treatment given an indication (current drug use: 47.6%, 95% CI 44.3-51.0%; full panic symptoms: 50.8%, 95% CI 48.0-53.6%), or have evidence of remitted depression when treated (22.3%, 95% CI 18.5-26.6%; and 7.3%, 95% CI 5.5-9.6%, respectively). In a multivariable model, drug use and panic symptoms were independently associated with poorer outcomes along the depression treatment cascade. Few differences were evident by alcohol use. Current drug users were most likely to have an indication for depression treatment, but were least likely to be receiving treatment or to have remitted depression. These same disparities were even more starkly evident among patients with co-occurring symptoms of panic disorder compared to those without. Achieving improvements in the depression treatment cascade will likely require attention to substance use and psychiatric comorbidities.

Suicidal Ideation is Associated with Limited Engagement in HIV Care.

PHQ-9 data from persons living with HIV (PLWH, n = 4099) being screened for depression in three clinics in the southeastern USA were used to determine the prevalence of suicidal ideation (SI). SI was reported by 352 (8.6 %); associated with <3 years since HIV diagnosis (1.69; 95 %CI 1.35, 2.13), and HIV RNA >50 copies/ml (1.70, 95 %CI 1.35, 2.14). Data from PLWH enrolled in a depression treatment study were used to determine the association between moderate-to-high risk SI (severity) and SI frequency reported on PHQ-9 screening. Over forty percent of persons reporting that SI occurred on "more than half the days" (by the PHQ-9) were assessed as having a moderate-to-high risk for suicide completion during the Mini International Neuropsychiatric Interview. SI, including moderate-to-high risk SI, remains a significant comorbid problem for PLWH who are not fully stabilized in care (as indicated by detectable HIV RNA or HIV diagnosis for less than 3 years).

Using Patient Perspectives to Inform the Development of a Behavioral Intervention for Chronic Pain in Patients with HIV: A Qualitative Study.

Background: Chronic pain is a common and disabling comorbidity in individuals living with HIV. Behavioral interventions are among the most effective and safe nonpharmacologic treatments for chronic pain. However, the success of a behavioral intervention is influenced by how well it is tailored to the target population's biological, psychological, and social context. Given well-documented psychosocial vulnerabilities among persons with HIV, it is critical to develop a behavioral intervention for chronic pain tailored to this population. Objective: To use qualitative methods to investigate patient preferences for the structure and delivery of a behavioral intervention for chronic pain in individuals with HIV. Methods: Interviews and focus groups were used to elicit participant preferences. A thematic analysis approach, with an initial round of open coding, was used to develop the codebook and analyze the data. Results: Qualitative data from 12 interviews and 3 focus groups with patients living with HIV and chronic pain (total N = 24) were analyzed. Emergent themes fell into four major categories: perceived value of group sessions, incorporating peer leadership, and two key elements of how the intervention should be delivered: the HIV status of group participants and views on phone-delivered intervention content. Discussion: This study provides a framework for the structure and delivery of a behavioral intervention for chronic pain in individuals with HIV based on patient preferences. We will use these results to design our intervention, and hope that our approach informs the work of investigators in other disciplines who seek to incorporate patient preferences during intervention development.

Improvements in depression and changes in quality of life among HIV-infected adults.

Improving quality of life (QOL) for HIV-infected individuals is an important objective of HIV care, given the considerable physical and emotional burden associated with living with HIV. Although worse QOL has been associated with depression, no research has quantified the potential of improvement in depression to prospectively improve QOL among HIV-infected adults. We analyzed data from 115 HIV-infected adults with depression enrolled in a randomized controlled trial to evaluate the effectiveness of improved depression care on antiretroviral drug adherence. Improvement in depression, the exposure of interest, was defined as the relative change in depression at six months compared to baseline and categorized as full response (≥50% improvement), partial response (25-49% improvement), and no response (<25% improvement). Multivariable linear regression was used to investigate the relationship between improvement in depression and four continuous measures of QOL at six months: physical QOL, mental QOL, HIV symptoms, and fatigue intensity. In multivariable analyses, physical QOL was higher among partial responders (mean difference [MD] = 2.51, 95% CI: -1.51, 6.54) and full responders (MD = 3.68, 95% CI: -0.36, 7.72) compared to individuals who did not respond. Mental QOL was an average of 4.01 points higher (95% CI: -1.01, 9.03) among partial responders and 14.34 points higher (95% CI: 9.42, 19.25) among full responders. HIV symptoms were lower for partial responders (MD = -0.69; 95% CI: -1.69, 0.30) and full responders (MD = -1.51; 95% CI: -2.50, -0.53). Fatigue intensity was also lower for partial responders (MD = -0.94; 95% CI: -1.94, 0.07) and full responders (MD = -3.00; 95% CI: -3.98, -2.02). Among HIV-infected adults with depression, improving access to high-quality depression treatment may also improve important QOL outcomes.

A Disability-Inclusive Healthcare-to-Well-Being Translational Science Framework.

The recent World Health Organization report on disability noted that people with disabilities (PWD) have many unmet health and rehabilitation needs, face numerous barriers to accessing healthcare and specialized services, and have overall worse health than people without disability. In view of this urgency to better identify and address health inequities systematically, we convened an expert panel of 14 stakeholders to develop a strategic plan that addresses this issue. The panel identified two major obstacles to quality healthcare services for PWD: (1) lack of coordination between the various healthcare sectors and community well-being programs and (2) substantial challenges finding and accessing healthcare services that meet their specific needs. The expert stakeholder panel noted that well-being self-management programs (both online and in person) that are easily accessible to PWD are critically needed. PWD must transition from being cared for as patients to individuals who are able to self-manage and self-advocate for their own health and well-being plans and activities. The proposed strategic plan offers providers and local communities a framework to begin addressing accessible and appropriate healthcare-to-well-being services and programs for PWD in managing their health in partnership with their healthcare providers.

Effects of an intervention on internalized HIV-related stigma for individuals newly entering HIV care.

OBJECTIVE: Considering the association between internalized HIV-related stigma and treatment adherence, an intervention addressing HIV treatment adherence may have the added benefit of reducing internalized stigma. The 'integrating ENGagement and Adherence Goals upon Entry' (iENGAGE) intervention was developed to facilitate adjustment to living with HIV among individuals newly engaged in HIV care. We evaluated the effects of this intervention on internalized stigma and examined whether the effect is moderated by depressive symptoms and coping styles. DESIGN: The iENGAGE intervention was tailored individually to improve information, motivation, and behavioral skills to promote treatment adherence and viral suppression. Three hundred and seventy-one participants initiating HIV care at four sites in the United States were randomly assigned to either the intervention receiving four face-to-face sessions or standard of care control arm. METHODS: Baseline and 48-week follow-up assessments were conducted, which included validated measures of internalized HIV-related stigma, depressive symptoms, and coping mechanisms (behavioral disengagement and self-blame) as secondary outcomes. A repeated measures ANOVA evaluated the effect of the intervention on change in internalized HIV stigma. Furthermore, the moderating effects of depressive symptoms and coping mechanisms on the decrease in internalized stigma were examined. RESULTS: The decrease in internalized stigma from baseline to 48 weeks was significantly larger in the intervention arm compared with the control arm. This effect was significantly moderated by baseline levels of depressive symptoms and self-blame. CONCLUSION: The multifaceted iENGAGE intervention is effective in reducing internalized stigma for new-to-HIV care individuals, especially with higher depressive symptoms or when using higher levels of self-blame coping.

Complexities of HIV Disclosure in Patients Newly Entering HIV Care: A Qualitative Analysis.

The role of HIV disclosure and its influence on engagement in HIV care after initial linkage to care is not well understood. We conducted 28 in-depth interviews with patients newly entering HIV care. Gaining access to social support was a key reason that many patients disclosed their HIV status. For some, HIV disclosure improved support networks related to engagement in care at the time of care entry, in the form of appointment reminders, emotional support, and confidence to disclose more widely. However, some participants cited anticipated stigma as a barrier to disclosure, as they feared rejection or further disclosure without their permission. Early access to social support and skill building related to stigma reduction and coping can be useful resources to help patients manage HIV, as they initiate care. In addition, incorporating support for smart disclosure decisions into interventions may improve access to social support, ultimately improving engagement in care.

Factors Associated with HIV Disclosure Status Among iENGAGE Cohort of New to HIV Care Patients.

HIV disclosure is an important behavior with implications for HIV treatment and prevention but understudied among new to HIV care patients who face unique challenges adjusting to a new diagnosis. This study evaluated the factors associated with HIV disclosure status and patterns of HIV disclosure among new to HIV care patients. A cross-sectional study was conducted evaluating the iENGAGE (integrating ENGagement and Adherence Goals upon Entry) cohort. Participants were enrolled in this randomized behavioral trial between December 2013 and June 2016. The primary and secondary outcomes included HIV disclosure status (Yes/No) and patterns of disclosure (Broad, Selective and Nondisclosure), respectively. Logistic and Multinomial Logistic Regression were used to evaluate the association of participant factors with HIV disclosure and patterns of HIV disclosure, respectively. Of 371 participants, the average age was 37 ± 12 years, 79.3% were males, and 62.3% were African Americans. A majority of participants (78.4%) disclosed their HIV status at baseline, 63.1% were broad disclosers and 15.2% were selective disclosers. In multivariable regression, black race, emotional support, and unmet needs predicted any HIV and broad disclosure, whereas males, emotional support, active coping, and acceptance were associated with selective disclosure. Interventions to promote early disclosure should focus on coping strategies and unmet needs, particularly among black and male people living with HIV initiating care.

Long-term survival of 1338 MM patients treated with tandem autologous vs. autologous-allogeneic transplantation.

Contrary to tandem autologous transplant (auto-auto), autologous followed by reduced intensity conditioning allogenic transplantation (auto-allo) offers graft-versus-myeloma (GVM) effect but with higher toxicity. Trials comparing these two strategies relied on availability of HLA-matched sibling donors for arm allocation (biological randomization) and yielded conflicting results. A pooled analysis of multiple trials with extended follow up provides an opportunity to compare these strategies. We obtained individual patient data from participants of four trials comparing auto-auto vs. auto-allo after induction therapy. There were 899 patients in auto-auto and 439 in auto-allo. Median follow up of survivors was 118.5 months. Median overall survival (OS) was 78.0 months in auto-auto and 98.3 months in auto-allo (HR = 0.84, P = 0.02). OS was 36.4% vs. 44.1% at 10 years (P = 0.01) for auto-auto and auto-allo, respectively. Progression-free survival was also improved in auto-allo (HR = 0.84, P = 0.004). Risk of non-relapse mortality was higher in auto-allo (10 year 8.3% vs. 19.7%, P < 0.001), while risk of disease progression was higher in auto-auto (10 year 77.2% vs. 61.6%, P < 0.001). Median post relapse survival was 41.5 months in auto-auto and 62.3 months in auto-allo (HR = 0.71, P < 0.001). This supports the existence of durable GVM effect enhancing myeloma control with subsequent therapies.

A Web-Based Data Collection Platform for Multisite Randomized Behavioral Intervention Trials: Development, Key Software Features, and Results of a User Survey.

BACKGROUND: Meticulous tracking of study data must begin early in the study recruitment phase and must account for regulatory compliance, minimize missing data, and provide high information integrity and/or reduction of errors. In behavioral intervention trials, participants typically complete several study procedures at different time points. Among HIV-infected patients, behavioral interventions can favorably affect health outcomes. In order to empower newly diagnosed HIV positive individuals to learn skills to enhance retention in HIV care, we developed the behavioral health intervention Integrating ENGagement and Adherence Goals upon Entry (iENGAGE) funded by the National Institute of Allergy and Infectious Diseases (NIAID), where we deployed an in-clinic behavioral health intervention in 4 urban HIV outpatient clinics in the United States. To scale our intervention strategy homogenously across sites, we developed software that would function as a behavioral sciences research platform. OBJECTIVE: This manuscript aimed to: (1) describe the design and implementation of a Web-based software application to facilitate deployment of a multisite behavioral science intervention; and (2) report on results of a survey to capture end-user perspectives of the impact of this platform on the conduct of a behavioral intervention trial. METHODS: In order to support the implementation of the NIAID-funded trial iENGAGE, we developed software to deploy a 4-site behavioral intervention for new clinic patients with HIV/AIDS. We integrated the study coordinator into the informatics team to participate in the software development process. Here, we report the key software features and the results of the 25-item survey to evaluate user perspectives on research and intervention activities specific to the iENGAGE trial (N=13). RESULTS: The key features addressed are study enrollment, participant randomization, real-time data collection, facilitation of longitudinal workflow, reporting, and reusability. We found 100% user agreement (13/13) that participation in the database design and/or testing phase made it easier to understand user roles and responsibilities and recommended participation of research teams in developing databases for future studies. Users acknowledged ease of use, color flags, longitudinal work flow, and data storage in one location as the most useful features of the software platform and issues related to saving participant forms, security restrictions, and worklist layout as least useful features. CONCLUSIONS: The successful development of the iENGAGE behavioral science research platform validated an approach of early and continuous involvement of the study team in design development. In addition, we recommend post-hoc collection of data from users as this led to important insights on how to enhance future software and inform standard clinical practices. TRIAL REGISTRATION: Clinicaltrials.gov NCT01900236; (https://clinicaltrials.gov/ct2/show/NCT01900236 (Archived by WebCite at http://www.webcitation.org/6qAa8ld7v).

Ongoing life stressors and suicidal ideation among HIV-infected adults with depression.

BACKGROUND: Suicidal ideation is the most proximal risk factor for suicide and can indicate extreme psychological distress; identification of its predictors is important for possible intervention. Depression and stressful or traumatic life events (STLEs), which are more common among HIV-infected individuals than the general population, may serve as triggers for suicidal thoughts. METHODS: A randomized controlled trial testing the effect of evidence-based decision support for depression treatment on antiretroviral adherence (the SLAM DUNC study) included monthly assessments of incident STLEs, and quarterly assessments of suicidal ideation (SI). We examined the association between STLEs and SI during up to one year of follow-up among 289 Southeastern US-based participants active in the study between 7/1/2011 and 4/1/2014, accounting for time-varying confounding by depressive severity with the use of marginal structural models. RESULTS: Participants were mostly male (70%) and black (62%), with a median age of 45 years, and experienced a mean of 2.36 total STLEs (range: 0-12) and 0.48 severe STLEs (range: 0-3) per month. Every additional STLE was associated with an increase in SI prevalence of 7% (prevalence ratio (PR) (95% confidence interval (CI)): 1.07 (1.00, 1.14)), and every additional severe STLE with an increase in SI prevalence of 19% (RR (95% CI): 1.19 (1.00, 1.42)). LIMITATIONS: There was a substantial amount of missing data and the exposures and outcomes were obtained via self-report; methods were tailored to address these potential limitations. CONCLUSIONS: STLEs were associated with increased SI prevalence, which is an important risk factor for suicide attempts and completions.

Venous thromboembolism among HIV-positive patients and anticoagulation clinic outcomes integrated within the HIV primary care setting.

The purpose of this study was to explore factors associated with venous thromboembolism (VTE) among a cohort of HIV-infected patients and to describe early outcomes of warfarin anticoagulation therapy treated in a pharmacist-based anticoagulation clinic (ACC). A nested case-control study was conducted using the University of Alabama at Birmingham 1917 HIV Clinic Cohort. Conditional logistic regression was used to estimate factors associated with VTE. Among HIV-infected VTE cases, ACC-managed patients were compared to primary care provider (PCP)-managed patients to determine Time within Therapeutic INR Range (TTR). CD4 < 200 cells/µl (OR = 4.50; 95% CI = 1.52, 13.37; p = 0.007) and prior surgical procedures (13.20; 1.56; 111.4; p = 0.018) demonstrated positive associations with VTE, whereas longer HIV duration demonstrated a negative association (0.87; 0.78, 0.98; p = 0.019). TTR was 56.2% among ACC-managed patients compared to 30.5% of PCP-managed patients (p = 0.174). Overall, prior surgical procedures and low CD4 count were associated with an increased risk of VTE among HIV-infected patients. Despite small sample size, patients managed in ACC tend to achieve greater proportion of TTR compared to those managed by PCPs, suggesting that this model of therapy may provide additional benefits to HIV-infected patients.

Implementation of PHQ-9 depression screening for HIV-infected patients in a real-world setting.

The prevalence of depression is 20%-30% for people living with HIV, and while it is associated with poorer adherence to antiretrovirals, it is often unrecognized by medical providers. Although it has been challenging for some health care settings to develop consistent depression screening mechanisms, it is feasible to create screening protocols using the nine-item Patient Health Questionnaire (PHQ-9). Establishing a depression screening and response protocol is an iterative process that involves preparing staff, determining screening frequency, and developing procedures for response and appropriate medical record documentation. While there are multiple issues and potential challenges during implementation, it is possible to incorporate systematic depression screening into HIV primary care in a manner that achieves staff buy-in, minimizes patient burden, streamlines communication, and efficiently uses the resources available in the medical setting.

Treating depression within the HIV "medical home": a guided algorithm for antidepressant management by HIV clinicians.

People living with HIV/AIDS (PLWHA) suffer increased depression prevalence compared to the general population, which negatively impacts antiretroviral (ART) adherence and HIV-related outcomes leading to morbidity and mortality. Yet depression in this population often goes undiagnosed and untreated. The current project sought to design an evidence-based approach to integrate depression care in HIV clinics. The model chosen, measurement-based care (MBC), is based on existing guidelines and the largest randomized trial of depression treatment. MBC was adapted to clinical realities of HIV care for use in a randomized controlled effectiveness trial of depression management at three academic HIV clinics. The adaptation accounts for drug-drug interactions critical to ongoing ART effectiveness and can be delivered by a multidisciplinary team of nonmental health providers. A treatment algorithm was developed that enables clinically supervised, nonphysician depression care managers (DCMs) to track and monitor antidepressant tolerability and treatment response while supporting nonpsychiatric prescribers with antidepressant choice and dosing. Quality of care is ensured through weekly supervision of DCMs by psychiatrists. Key areas of flexibility that have been important in implementation have included flexibility in timing of assessments, accommodation of divergence between algorithm recommendations and provider decisions, and accommodation of delays in implementing treatment plans. This adaptation of the MBC model to HIV care has accounted for critical antidepressant-antiretroviral interactions and facilitated the provision of quality antidepressant management within the HIV medical home.

Assessing the effect of Measurement-Based Care depression treatment on HIV medication adherence and health outcomes: rationale and design of the SLAM DUNC Study.

Depression affects 20-30% of people living with HIV/AIDS (PLWHA) in the U.S. and predicts greater sexual risk behaviors, lower antiretroviral (ARV) medication adherence, and worse clinical outcomes. Yet little experimental evidence addresses the critical clinical question of whether depression treatment improves ARV adherence and clinical outcomes in PLWHA with depression. The Strategies to Link Antidepressant and Antiretroviral Management at Duke, UAB, and UNC (SLAM DUNC) Study is a randomized clinical effectiveness trial funded by the National Institute for Mental Health. The objective of SLAM DUNC is to test whether a depression treatment program integrated into routine HIV clinical care affects ARV adherence. PLWHA with depression (n=390) are randomized to enhanced usual care or a depression treatment model called Measurement-Based Care (MBC). MBC deploys a clinically supervised Depression Care Manager (DCM) to provide evidence-based antidepressant treatment recommendations to a non-psychiatric prescribing provider, guided by systematic and ongoing measures of depressive symptoms and side effects. MBC has limited time requirements and the DCM role can be effectively filled by a range of personnel given appropriate training and supervision, enhancing replicability. In SLAM DUNC, MBC is integrated into HIV care to support HIV providers in antidepressant prescription and management. The primary endpoint is ARV adherence measured by unannounced telephone-based pill counts at 6 months with follow-up to 12 months and secondary endpoints including viral load, health care utilization, and depressive severity. Important outcomes of this study will be evidence of the effectiveness of MBC in treating depression in PLWHA and improving HIV-related outcomes.