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A workshop was sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases to focus on research gaps and opportunities in pancreatic pain. The event was held on July 21, 2021, and structured into 4 sessions: (1) pathophysiology; (2) biomarkers, mediators, and pharmacology of pain; (3) pain assessment; and (4) pain treatment challenges and opportunities. The current state of knowledge was reviewed; many knowledge gaps and research needs were identified that require further investigation. Common themes included the need to better understand the underlying mechanisms of pain in pancreatic diseases, the relationship of visceral neural pathways and central pain centers, the role of behavioral factors and disorders on the perception of pain, and differences in pain perception and processes in children when compared with adults. In addition, the role of genetic risk factors for pain and the mechanisms and role of placebos in pain treatment were discussed. Methods of pain assessment including quantitative sensory testing were examined, as well as the process of central sensitization of pain. Finally, newer approaches to pain management including cognitive behavioral therapy, nerve stimulation, experimental (nonopioid) drugs, and cannabinoid compounds were covered.

Studies suggest that inflammation might be involved in the pathogenesis of depression. Individuals with human immunodeficiency virus (HIV) have a higher risk of depression and elevated inflammatory profiles. Despite this, research on the link between inflammation and depression among this high-risk population is limited. We examined a sample of men who have sex with men from the Multicenter AIDS Cohort Study in prospective analyses of the association between inflammation and clinically relevant depression symptoms, defined as scores >20 on Center for Epidemiological Studies Depression Scale. We included 1,727 participants who contributed 9,287 person-visits from 1984 to 2010 (8,218 with HIV (HIV+) and 1,069 without (HIV−)). Exploratory factor analysis (EFA) was used to characterize underlying inflammatory processes from 19 immune markers. Logistic regression with generalized estimating equations was used to evaluate associations between inflammatory processes and depressive symptoms stratified by HIV serostatus. Three EFA-identified inflammatory processes (EIPs) were identified. EIP-1 scores—described by soluble tumor necrosis factor receptor 2 (sTNF-R2), soluble interleukin-2 receptor α (sIL-2Rα), sCD27, B-cell activating factor, interferon γ-induced protein 10 (IP-10), soluble interleukin-6 receptor (sIL-6R), sCD14, and sGP130—were significantly associated with 9% higher odds of depressive symptoms in HIV+ participants (odds ratio = 1.09; 95% confidence interval: 1.03, 1.16) and 33% higher odds in HIV− participants (odds ratio = 1.33; 95% confidence interval: 1.09, 1.61). Findings suggest that immune activation might be involved in depression risk among both HIV+ and HIV− men who have sex with men.

The term “gastroparesis” implies a partial or complete paralysis of the stomach as a result of muscle or nerve dysfunction. As this book will attest, gastroparesis is far more complex than this simple definition. Gastric emptying time may be normal and yet the patient may respond to the same treatments that work for other patients with study proven delayed gastric emptying. Is gastroparesis caused by dysbiosis, is it an autonomic neuropathic disorder, an autoimmune disorder, a problem of behavioral conditioning, or a central nervous system disorder? Patients may experience overlapping symptoms of nausea, vomiting, distension, abdominal pain, dysmotility, weight loss, early satiety, reflux, and others. This may generate a complex differential diagnosis that includes other conditions such as rumination, functional dyspepsia, somatization, eating disorder, and even Munchausen’s syndrome, to name but a few. Psychiatric conditions can occur as a result of gastroparesis, may be a causative or exacerbating factor in gastroparesis, and may confound the diagnosis and treatment of gastroparesis.

Psychiatric comorbidity profoundly affects outcomes in chronic pain. Chronic pain alters the clinical appearance of psychiatric conditions. Problems of poor coping, limited life skills, poor social and behavioral modeling, limited resources, and poor self-efficacy all can complicate and exacerbate chronic pain disorders. Operant and classical mechanisms with inadvertent rewards for illness-related behaviors condition the behaviors associated with chronic pain. Iatrogenic addiction can also make it difficult for patients to engage in functional rehabilitation. Features of temperament, including extraversion and instability, lead to maladaptive responses to managing pain and difficulty engaging with physicians and health care professionals. Lastly, diseases of mood decrease the normal capacity to experience rewards associated with healthy behavior and divert patients toward avoidance coping, nihilistic views of recovery, and disengagement from support systems and medical care. A coherent and comprehensive diagnostic formulation including these elements leads to effective interdisciplinary rehabilitative pain treatment.

Background Although cocaine use may induce/accelerate HIV-associated comorbidities in HIV-infected individuals on antiretroviral therapy (ART), and that HIV itself may accelerate aging, the issue of whether cocaine use plays a role in HIV-associated aging in HIV-infected cocaine users has not been reported. The goals of this study were (1) to explore factor(s) associated with peripheral blood leukocyte telomere length, a marker of cellular replicative history, and telomere shortening in HIV-infected individuals, and (2) to assess whether cocaine use plays a role in accelerating telomere shortening in cocaine users with HIV infection. Methods Between June 2010 and December 2016, 147 HIV-infected participants in Baltimore, Maryland, were enrolled in a cross-sectional study investigating factor(s) associated with telomere length. Of these 147, 93 participated in a follow-up study to examine factor(s) associated with telomere shortening. Robust regression model was used to analyze cross-sectional data and the generalized estimating equation approach was used to analyze follow-up data. Results Cross-sectional analyses demonstrated that (1) both daily alcohol consumption and use of non-nucleoside reverse transcriptase inhibitors (NNRTIs) were independently associated with telomere length, and cocaine use modified the associations of daily alcohol use and NNRTI use with telomere length. Longitudinal analyses suggested that both daily alcohol consumption and duration of NNRTI use were independently associated with telomere shortening, and (2) cocaine use induced/accelerated telomere shortening in HIV-infected individuals. Conclusions Our findings suggest that cocaine use may promote premature aging in HIV-infected individuals who are on ART. Our results emphasize the importance of cocaine abstinence/reduced use, which may retard HIV-associated premature aging.

Pain has always been an important part of human immunodeficiency virus (HIV) disease and its experience for patients. In this guideline, we review the types of chronic pain commonly seen among persons living with HIV (PLWH) and review the limited evidence base for treatment of chronic noncancer pain in this population. We also review the management of chronic pain in special populations of PLWH, including persons with substance use and mental health disorders. Finally, a general review of possible pharmacokinetic interactions is included to assist the HIV clinician in the treatment of chronic pain in this population. It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. The Infectious Diseases Society of American considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient’s individual circumstances.

Pain has always been an important part of human immunodeficiency virus (HIV) disease and its experience for patients. In this guideline, we review the types of chronic pain commonly seen among persons living with HIV (PLWH) and review the limited evidence base for treatment of chronic noncancer pain in this population. We also review the management of chronic pain in special populations of PLWH, including persons with substance use and mental health disorders. Finally, a general review of possible pharmacokinetic interactions is included to assist the HIV clinician in the treatment of chronic pain in this population.It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. The Infectious Diseases Society of American considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.

Background It has been recognized that myocardial and hepatic steatosis may be more prevalent in HIV-infected individuals on antiretroviral therapy (ART); however, factors associated with these conditions have not been thoroughly investigated. The goals of this study were (1) to identify the risk factors for myocardial and hepatic steatosis in HIV-infected African Americans (AAs) and explore whether ART use is independently associated with myocardial and hepatic steatosis, and (2) to examine whether and how cocaine use influences any associations of ART use with myocardial and hepatic steatosis. Methods Between June 2010 and December 2013, 220 HIV-infected AAs in Baltimore, Maryland, were enrolled in a study investigating HIV/ART-associated myocardial and hepatic damage. Proton magnetic resonance spectroscopy was performed to quantify myocardial and hepatic triglyceride contents. Sociodemographic, medical and laboratory data were also obtained. Robust regression model was employed to perform primary statistical analysis. Results Robust regression analyses showed that (1) duration of protease inhibitor (PI) use was independently associated with myocardial and hepatic triglyceride contents, (2) duration of PI use was independently associated with myocardial triglyceride in cocaine users (p = 0.025), but not in cocaine never-users (p = 0.84), and (3) duration of PI use was independently associated with hepatic triglyceride in cocaine users, but not in cocaine never-users (p = 0.52). Conclusions Cocaine use may trigger/exacerbate the toxicity of PI in ART-associated myocardial and hepatic steatosis, suggesting that cocaine abstinence/reduced use may retard these ART-associated comorbidities. Clinical trials should be conducted to examine whether reduced cocaine use improves HIV/AIDS-associated myocardial and hepatic steatosis.

Introduction Mental health care may mitigate negative consequences related to substance use and bolster engagement in care for drug dependence. Despite the increased risk of depression among people who inject drugs (PWID), the longitudinal relationship of depression symptoms with depression and drug treatment utilization in this population remains uncharacterized. Methods Data on depressive symptoms and depression treatment from current and former PWID in the ALIVE (AIDS Linked to the IntraVenous Experience) community-based cohort who had ≥3 study visits from July 2005 to June 2016 were included. We used logistic regression analysis with generalized estimating equations to examine factors associated with depression treatment in the 12 months following reported major depressive symptoms (CES-D ≥ 23) in the absence of treatment. We further examined the association between depression, depression treatment, and subsequent engagement in drug treatment among those with active substance use or alcohol dependence. Results Of the 1544 participants, 34% were female, the median age was 51 years, and 91% were African-American. PWID reported major depressive symptoms at 22% of study visits. In adjusted analysis, acute emergency care, suicidal ideation, and recent alcohol or drug treatment were positively associated with initiating depression treatment. Depression was positively associated with subsequent treatment for substance dependence among those actively using (aOR = 1.30, 95% CI: 1.10–1.53). Conclusions PWID experience a high burden of depressive symptoms with significant unmet need of treatment for depression. Our findings suggest that mental health providers should bolster connections to chronic disease and alcohol and drug treatment providers.

The development of antiretroviral therapy (ART) has dramatically increased the lifespan of HIV patients but treatment is complicated by numerous adverse effects and toxicities. ART complications include neuropsychiatric, metabolic, gastrointestinal, cardiac, and numerous other toxicities, and clinicians often have to choose one toxicity over another to offer the best medication regimen for a patient. Some antiviral drugs cause significant neuropsychiatric complications, including depression, cognitive impairment, and sleep disturbance. Even in careful studies, it may be difficult to determine which effects are related to the virus, the immune system, or the treatment. Of the six currently marketed classes of antiviral drugs, the nucleoside reverse transcriptase inhibitors and the non-nucleoside reverse transcriptase inhibitors have been most commonly associated with neuropsychiatric complications. Within these classes, certain drugs are more likely to cause difficulty than others. We review the contention regarding the central nervous system (CNS) complications of efavirenz, as well as debate about the role of CNS penetration in drug effectiveness and toxicity. A thorough working knowledge of the neuropsychiatric consequences of ART allows clinicians to tailor treatment more successfully to individual patients as well as to identify ART more quickly as the source of a problem or symptom.

Mobile devices, digital technologies, and web-based applications—known collectively as eHealth (electronic health)—could improve health care delivery for costly, chronic diseases such as schizophrenia. Pharmacologic and psychosocial therapies represent the primary treatment for individuals with schizophrenia; however, extensive resources are required to support adherence, facilitate continuity of care, and prevent relapse and its sequelae. This paper addresses the use of eHealth in the management of schizophrenia based on a roundtable discussion with a panel of experts, which included psychiatrists, a medical technology innovator, a mental health advocate, a family caregiver, a health policy maker, and a third-party payor. The expert panel discussed the uses, benefits, and limitations of emerging eHealth with the capability to integrate care and extend service accessibility, monitor patient status in real time, enhance medication adherence, and empower patients to take a more active role in managing their disease. In summary, to support this technological future, eHealth requires significant research regarding implementation, patient barriers, policy, and funding.

ObjectivesCenter of Epidemiologic Studies-Depression Scale (CES-D) provides a snapshot of symptom severity at a single point in time. However, the best way of using CES-D to classify long-term depression is unclear.MethodTo identify long-term depression among HIV-infected and HIV-uninfected 50+ year-old men who have sex with men (MSM) with at least 5years of follow-up, we compared sensitivities and specificities of CES-D-based metrics (baseline CES-D; four consecutive CES-Ds; group-based trajectory models) thresholded at 16 and 20 to a clinician's evaluation of depression phenotype based on all available data including CES-D history, depression treatment history, drug use history, HIV disease factors, and demographic characteristics.ResultsA positive depressive phenotype prevalence was common among HIV-infected (prevalence = 33.1%) and HIV-uninfected MSM (prevalence = 23.2%). Compared to the depressive phenotype, trajectory models of CES-D≥20 provided highest specificities among HIV-infected (specificity = 99.9%, 95% Confidence Interval [CI]:99.4%-100.0%) and HIV-uninfected MSM (specificity = 99.0%, 95% CI:97.4%-99.7%). Highest sensitivities resulted from classifying baseline CES-D≥16 among HIV-infected MSM (sensitivity = 75.0%, 95% CI:67.3%-81.7%) and four consecutive CES-Ds≥16 among HIV-uninfected MSM (sensitivity = 81.0%, 95% CI:73.7%-87.0%).ConclusionChoice of method should vary, depending on importance of false positive or negative rate for long-term depression in HIV-infected and HIV-uninfected MSM.

OBJECTIVES Cardiac steatosis is a manifestation of ectopic fat deposition and is associated with obesity. The impact of chronic cocaine use on obesity measures and on the relationship between obesity measures and cardiac steatosis is not well-characterized. The objectives of this study were to compare obesity measures in chronic cocaine users and nonusers, and to explore which factors, in addition to obesity measures, are associated with myocardial triglyceride in African Americans, using noninvasive magnetic resonance spectroscopy. METHODS Between June 2004 and January 2014, 180 healthy African American adults without HIV infection, hypertension, and diabetes were enrolled in an observational proton magnetic resonance spectroscopy and imaging study investigating factors associated with cardiac steatosis. RESULTS Among these 180 participants, 80 were chronic cocaine users and 100 were nonusers. The median age was 42 (interquartile range, 34-47) years. Obesity measures trended higher in cocaine users than in nonusers. The median myocardial triglyceride was 0.6% (interquartile range, 0.4%-1.1%). Among the factors investigated, years of cocaine use, leptin, and visceral fat were independently associated with myocardial triglyceride. Body mass index and visceral fat, which were significantly associated with myocardial triglyceride in noncocaine users, were not associated with myocardial triglyceride content in cocaine users. CONCLUSIONS This study shows (1) cocaine users may have more fat than nonusers and (2) myocardial triglyceride is independently associated with duration of cocaine use, leptin, and visceral fat in all subjects, whereas leptin and high-density lipoprotein cholesterol, but not visceral fat or body mass index, in cocaine users, suggesting that chronic cocaine use may modify the relationships between obesity measures and myocardial triglyceride.

The advent of highly active antiretroviral therapy has prolonged the life expectancy of HIV patients and decreased the number of adults who progress to AIDS and HIV-associated dementia. However, neurocognitive deficits remain a pronounced consequence of HIV/AIDS. HIV-1 infection targets the central nervous system in subcortical brain areas and leads to high rates of delirium, depression, opportunistic central nervous system infections, and dementia. Long-term HIV replication in the brain occurs in astrocytes and microglia, allowing the virus to hide from antiviral medication and later compromise neuronal function. The associated cognitive disturbance is linked to both viral activity and inflammatory and other mediators from these immune cells that lead to the damage associated with HIV-associated neurocognitive disorders, a general term given for these disturbances. We review the severity and prevalence of the neuropsychiatric complications of HIV including delirium, neurobehavioral impairments (depression), minor cognitive-motor dysfunction, and HIV-associated dementia.

The risk behaviors that transmit HIV and complicate HIV treatment are often influenced by Axis II personality disorders and personality traits. There has been relatively little research, however, on the role of personality traits and disorders in HIV despite their stable, durable, and heritable influence on thoughts, feelings, and behavior. Certain traits, such as various types of extroversion and sensation seeking, appear to increase the likelihood of engaging in HIV risk behaviors, having poorer quality of life, and adhering to treatment regimens. Effective HIV prevention and treatment programs should consider specific personality traits that render some individuals more vulnerable to engaging in behaviors that endanger their health and the health of others. Recognizing these personality traits or disorders is useful in developing more specific, effective risk reduction strategies and improving overall health outcomes. This chapter describes personality traits and personality disorders that occur among HIV at-risk and HIV-infected individuals and the implications for HIV care.

Questionnaires of depressive symptoms assess symptom severity at one timepoint. However, we can evaluate the ability of metrics to identify individuals at risk of more clinically relevant long-term depression. Using a depressive phenotype (derived from a review of all relevant depression indicators) as a gold standard, we examined sensitivities and specificities of CES-D–based metrics (baseline CES-D; four consecutive CES-Ds; group-based trajectory models) thresholded at 16 and 20 in HIV-infected and HIV–uninfected older men who have sex with men (MSM). Compared to the depressive phenotype, trajectory models of CES-D≥20 provided highest specificities among HIV-infected (specificity=99.9%, 95% Confidence Interval [CI]:99.4%–100.0%) and HIV-uninfected MSM (specificity=99.0%, 95% CI:97.4%–99.7%). Highest sensitivities resulted from classifying baseline CES-D≥16 among HIV-infected MSM (sensitivity=75.0%, 95% CI:67.3%–81.7%) and four consecutive CES-Ds≥16 among HIV-uninfected MSM (sensitivity=81.0%, 95% CI:73.7%–87.0%). Choice of method depends on importance of false positive or negative rate for long-term depression.

Chronic pain is common in persons with HIV and is often associated with psychiatric illness and substance abuse. Current literature links psychiatric illness and substance abuse with worse HIV outcomes; however, the relationship of chronic pain, alone and in the context of psychiatric illness and substance abuse, to outcomes in HIV has not been described. To develop this new area of inquiry, we propose an adapted biopsychosocial framework specifically for chronic pain in HIV. This framework will describe these relationships and serve as a conceptual framework for future investigations.

Background The key objectives of this study were to examine whether HIV infection itself is associated with subclinical coronary atherosclerosis and the potential contributions of cocaine use and antiretroviral therapies ( ART s) to subclinical coronary artery disease ( CAD ) in HIV ‐infected persons. Methods and Results Between June 2004 and February 2015, 1429 African American ( AA ) adults with/without HIV infection in Baltimore, Maryland, were enrolled in an observational study of the effects of HIV infection, exposure to ART , and cocaine use on subclinical CAD . The prevalence of subclinical coronary atherosclerosis was 30.0% in HIV ‐uninfected and 33.7% in HIV ‐infected ( P =0.17). Stratified analyses revealed that compared to HIV ‐uninfected, HIV ‐infected ART naïve were at significantly lower risk for subclinical coronary atherosclerosis, whereas HIV ‐infected long‐term ART users (≥36 months) were at significantly higher risk. Thus, an overall nonsignificant association between subclinical coronary atherosclerosis and HIV was found. Furthermore, compared to those who were ART naïve, long‐term ART users (≥36 months) were at significantly higher risk for subclinical coronary atherosclerosis in chronic cocaine users, but not in those who never used cocaine. Cocaine use was independently associated with subclinical coronary atherosclerosis. Conclusions Overall, HIV infection, per se, was not associated with subclinical coronary atherosclerosis in this population. Cocaine use was prevalent in both HIV ‐infected and ‐uninfected individuals and itself was associated with subclinical disease. In addition, cocaine significantly elevated the risk for ART ‐associated subclinical coronary atherosclerosis. Treating cocaine addiction must be a high priority for managing HIV disease and preventing HIV / ART ‐associated subclinical and clinical CAD in individuals with HIV infection.

This study described characteristics, psychiatric diagnoses and response to treatment among patients in an outpatient HIV clinic who screened positive for depression. Depressed (25 %) were less likely to have private insurance, less likely to have suppressed HIV viral loads, had more anxiety symptoms, and were more likely to report current substance abuse than not depressed. Among depressed, 81.2 % met diagnostic criteria for a depressive disorder; 78 % for an anxiety disorder; 61 % for a substance use disorder; and 30 % for co-morbid anxiety, depression, and substance use disorders. Depressed received significantly more treatment for depression and less HIV primary care than not depressed patients. PHQ-9 total depression scores decreased by 0.63 from baseline to 6-month follow-up for every additional attended depression treatment visit. HIV clinics can routinely screen and treat depressive symptoms, but should consider accurate psychiatric diagnosis as well as co-occurring mental disorders.

Persons over age 50 are not only aging with human immunodeficiency virus (HIV) infection but also represent a high proportion of new HIV infections. Neuropsychiatric symptoms, including depression, cognitive impairment, and substance abuse, are very common in individuals infected with HIV. However, there is little understanding of the relationship between these HIV-related comorbid conditions in newly infected elderly patients compared to uninfected elderly and those who have survived after 20 years of HIV/AIDS. We summarize the current theories and research that link aging and HIV with psychiatric illnesses and identify emerging areas for improved research, treatment, and patient care.

Major depressive disorder (MDD) is one of the most prevalent illnesses associated with HIV infection, and negatively affects medication adherence, disease progression and mortality in HIV disease. Co-morbid treatment of major depression in HIV disease is the optimal therapeutic approach, but discriminating MDD from normal fluctuations in mood state, personality or physiology is difficult. Definitive diagnosis of MDD is critical for drug safety and for avoiding unnecessary exposure to psychotropic medications. HIV patients respond to antidepressant treatment like the general population, and medication adverse effects and patient adherence are the best predictors of treatment outcome. This review attempts to assist the medical provider with the diagnosis and treatment of MDD in HIV patients. We outline the initial steps in screening and psychiatric referral, the antidepressants that are particularly useful in HIV-infected patients, and the adverse effects and pharmacological strategies for overcoming potential barriers to medication adherence. Potential interactions between the various classes of antidepressants and HIV/antiretroviral therapy, as well as management of HIV medication-related psychiatric adverse effects, are also discussed.

HIV infection, depression, and cocaine use are independently associated with increased inflammatory signal production. There is increasing evidence about the role of inflammation in depression. In HIV disease, cocaine use may increase disease progression as well as alter T cell functioning resulting in cytokine activation and thereby increasing susceptibility to depression. We examined the association between cocaine use and depression among 447 African American persons infected with HIV who were frequent cocaine users or non-users, enrolled in an observational study in Baltimore, Maryland, between August 2003 and December 2012. The overall prevalence of depression was 40.9 % (183 of 447) participants. Among persons who were depressed, the prevalence of cocaine use was 81.4 % (149 of 183), compared to 69.3 % among persons who were not depressed (183 of 264), P = 0.004. Cocaine use was associated with nearly twofold increased odds of depression, unadjusted odds ratio (OR) 1.94, (95 % CI 1.23, 3.06); P = 0.004, compared to never using cocaine, and OR 1.02, (95 % CI 1.10, 1.05); P = 0.04 in adjusted analysis. A dose-response relationship between increasing duration of cocaine use and depression was observed. Frequency and duration of cocaine use may be associated with depression. We speculate that depression among cocaine users with HIV may involve an inflammatory component that needs further examination.

Major depressive disorder is the most common neuropsychiatric complication in human immunodeficiency virus (HIV) infections and is associated with worse clinical outcomes. We determined if detectable cerebrospinal fluid (CSF) HIV ribonucleic acid (RNA) at threshold ≥50 copies/ml is associated with increased risk of depression. The CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) cohort is a six-center US-based prospective cohort with bi-annual follow-up of 674 participants. We fit linear mixed models (N = 233) and discrete-time survival models (N = 154; 832 observations) to evaluate trajectories of Beck Depression Inventory (BDI) II scores and the incidence of new-onset moderate-to-severe depressive symptoms (BDI ≥ 17) among participants on combination antiretroviral therapy (cART), who were free of depression at study entry and received a minimum of three CSF examinations over 2496 person-months follow-up. Detectable CSF HIV RNA (threshold ≥50 copies/ml) at any visit was associated with a 4.7-fold increase in new-onset depression at subsequent visits adjusted for plasma HIV RNA and treatment adherence; hazard ratio (HR) = 4.76, (95 % CI 1.58–14.3); P = 0.006. Depression (BDI) scores were 2.53 points higher (95 % CI 0.47–4.60; P = 0.02) over 6 months if CSF HIV RNA was detectable at a prior study visit in fully adjusted models including age, sex, race, education, plasma HIV RNA, duration and adherence of CART, and lifetime depression diagnosis by Diagnostic Statistical Manual (DSM-IV) criteria. Persistent CSF but not plasma HIV RNA is associated with an increased risk for new-onset depression. Further research evaluating the role of immune activation and inflammatory markers may improve our understanding of this association.

Psychiatric disorders, particularly major depression, have a profound affect on the use of and adherence to highly active antiretroviral therapy (HAART) among patients with human immunodeficiency virus (HIV) infection. Because some of the symptoms of HIV infection are similar to those of major depression, efforts to diagnose and treat major depression are further complicated. Moreover, major depression increases vulnerability to HIV infection by provoking high-risk behaviors, and it interferes with a patient's ability to comply with protocols for the prevention and treatment of HIV infection. HIV infection itself can disguise, help initiate, or exacerbate major depression. In this report, the interrelation between major depression and HIV infection is evaluated, the impact of this interrelation on adherence to HAART is described, and methods for effective treatment of psychiatric conditions in HIV-infected persons are discussed.

Objectives Clinical and epidemiological evidence suggests that cocaine use is associated with an increased risk of premature atherosclerosis. The objectives of this study were to explore (1) whether cocaine abstinence is associated with a reduced marker of endothelial dysfunction, (2) whether cocaine abstinence is associated with a slower coronary plaque progression, and (3) whether reduction in cocaine use is associated with a reduced marker of endothelial dysfunction in African American chronic cocaine users with contrast-enhanced coronary CT angiography-confirmed less than 50% coronary stenosis. Methods Between March and June 2014, a total of 57 African American cocaine users with contrast-enhanced CT angiography-confirmed less than 50% coronary stenosis in Baltimore, Maryland, were enrolled in a 6-month follow-up study to investigate whether cocaine abstinence or reduction in cocaine use is associated with decreased endothelin-1 (ET-1) levels and coronary plaque progression at the 6-month follow-up. A voucher-based incentive approach was used to systematically reinforce cocaine abstinence, and urine benzoylecgonine test was implemented to confirm cocaine use. Results Among the 57 participants, 44 were HIV-infected. The median of duration of cocaine use was 18 (interquartile range, 7-30) years. According to generalized estimating equation analyses, both cocaine abstinence and reduction in cocaine use in the 6 months were independently associated with decreased ET-1. The incidence of coronary plaque progression was 7.4/100 person-years and 23.1/100 person-years in those who were totally abstinent from cocaine and those who continued to use cocaine, respectively. However, the difference in the incidence between these 2 groups was not significant (exact P = 0.30). Conclusions The findings of this study revealed a possible association of cocaine abstinence/reduction with lowered ET levels, which suggests that such changes in cocaine use might be beneficial for preventing endothelial damage. Further studies should be conducted to investigate whether ET-1 could be used as a marker for cocaine abstinence and reduction in cocaine use.

Patients with human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome have high rates of psychiatric illness. The effective management of these psychiatric conditions can improve a patient's quality of life and may improve antiretroviral adherence. Care providers for patients with HIV infection frequently encounter clinical situations in which psychotropic medications are needed or are being used. Those clinical situations require familiarity with the broad category of medications termed "psychotropic." That familiarity should include a basic understanding of indications, adverse effects, and drug interactions. In particular, it is very important to recognize the many potential interactions based on cytochrome P450 metabolism, which is common to many psychotropics, the protease inhibitors, and the nonnucleoside reverse-transcriptase inhibitors. In a brief review of the use of psychotropic medications in patients with HIV infection, we discuss indications, adverse effects, and drug interactions for commonly used antidepressants, mood stabilizers, anxiolytics, antipsychotics, psychostimulants, and drugs of abuse.

Patients with chronic pain and comorbid substance use disorders are at significantly greater risk for failure to achieve a successful outcome of either improved pain or improved function. This effect may be seen indirectly as well by the exclusion of patients with substance use disorders from many treatment trials for chronic pain disorders. The implication that substance abusers are more likely to be nonadherent to the treatment protocol and thus fail the therapy is clear. In practice, the presence of a substance use disorder in a patient’s medical record may influence the decisions of physicians regarding candidacy for particular therapies, such as corrective surgical procedures, medications with abuse potential, or relatively scarce high-cost technologies that require long-term commitments for follow-up. Pain management physicians may find patients with personality disorders difficult to treat. A model for the genesis and perpetuation of substance use disorders in patients with chronic pain that would refine treatment principles can be elucidated for this complicated population by including information about the patient’s temperament. This paper will outline the utility of examining temperament and how this information serves to transform the expectation of chronic pain treatment to one with a more therapeutically optimistic outcome.

Advances in highly active antiretroviral therapy (HAART) aim to improve the efficacy of HIV drugs as well as the quality of life in HIV-infected patients. Neurologic and psychologic disturbances that occur because of HIV disease and therapy are of great concern, and because they can overlap and are often difficult to distinguish, their pathogenesis is not clearly understood. Furthermore, these complications can lead to decreased adherence, thereby interfering with treatment outcomes. Antiretrovirals, including nonnucleoside reverse transcriptase inhibitors, can penetrate the central nervous system (CNS) and suppress viral replication, but they can also exacerbate CNS side effects and neuropsychiatric symptoms. When deciding which HAART drug combination is most appropriate for a patient, clinicians must consider the individual's risk of CNS complications together with the efficacy of the specific HAART regimen.

Safe and effective treatment of major depression, one of the most common comorbid conditions in individuals infected with HIV, significantly lowers morbidity and mortality from HIV disease. However, optimal treatment of both conditions is complicated by interactions between the disease processes as well as the pharmacological agents used to treat them. In patients with HIV it may be difficult to distinguish major depression from other physiological and emotional states that present with similar symptoms. Accurate diagnosis of major depression is thus complex and essential to preventing inappropriate exposure of patients to potentially harmful psychotropic medications. This review outlines important initial steps in making this diagnosis. All patients with HIV should be screened for depression by their medical providers and referred to a psychiatrist for full evaluation when necessary. The mainstay of treatment for major depression in patients with HIV disease is pharmacotherapy. Depressed patients with HIV respond to the same wide variety of antidepressant-class medications as depressed patients without HIV, including tricyclic antidepressants, paroxetine, fluoxetine and trazodone. Notably, new studies have also shown that some psychiatric medications can inhibit HIV replication. No particular antidepressant medication is superior for the treatment of depressed HIV-infected patients; however, the most important component of treatment of major depression in HIV-disease is patient adherence, which is highly influenced by antidepressant adverse effects. This review outlines adverse effects of antidepressant-class medications that are of particular concern in HIV-infected patients and describes pharmacological strategies for overcoming these potential barriers to medication adherence. This review also describes situations in which some adverse effects of antidepressant-class medications may be safely exploited to benefit depressed patients with HIV disease. Potential interactions between antidepressant-class medications and HIV medications, as well as pharmacological treatment strategies for treating the psychiatric adverse effects of HIV medications, are also discussed.

Detectable human immunodeficiency virus (HIV) RNA in the cerebrospinal fluid (CSF) is associated with central nervous system (CNS) complications. We developed the CSF HIV risk score through prediction modeling to estimate the risk of detectable CSF HIV RNA (threshold >50 copies/mL) to help identify persons who might benefit most from CSF monitoring. We used baseline data from 1,053 participants receiving combination antiretroviral therapy who were enrolled in the 6-center, US-based CNS HIV Antiretroviral Therapy Effects Research (CHARTER) prospective cohort in 2004–2007. Plasma HIV RNA, CNS penetration effectiveness, duration of combination antiretroviral therapy, medication adherence, race, and depression status were retained correlates of CSF HIV RNA, displaying good discrimination (C statistic = 0.90, 95% confidence interval (CI): 0.87, 0.93) and calibration (Hosmer-Lemeshow P = 0.85). The CSF HIV risk score ranges from 0 to 42 points, with a mean of 15.4 (standard deviation, 7.3) points. At risk scores greater than 25, the probability of detecting CSF HIV RNA was at least 42.9% (95% CI: 36.6, 49.6). For each 1-point increase, the odds of detecting CSF HIV RNA increased by 26% (odds ratio = 1.26, 95% CI: 1.21, 1.31; P < 0.01). The risk score correlates with detection of CSF HIV RNA. It represents an advance in HIV management and monitoring of CNS effects, providing a potentially useful tool for clinicians.

Major depression and demoralization are very common in patients with cancer. A discussion of the diagnostic specificity of major depression and demoralization (also known as adjustment disorder) is presented here, followed by a review of some effects of comorbid depression and cancer. Finally, there are a brief review of studies of antidepressant pharmacotherapy in cancer patients, a treatment algorithm for antidepressant therapy, and suggestions for treatment of demoralization.

This study assessed HIV risk behaviors and their association with psychiatric disorders among women prisoners.HIV risk behaviors practiced in the five years before incarceration were ascertained with the Risk Behavior Assessment interview for 177 inmates at the Maryland Correctional Institution for Women. The Structured Clinical Interview for the DSM-IV was used to determine the occurrence of posttraumatic stress disorder (PTSD), major depression, and dysthymic disorder among the women. Regression models were used to determine the association between HIV risk behavior and psychiatric disorders.HIV risk behaviors in the five years before incarceration included never or rarely having used condoms (56 percent of the women), injection drug use (42 percent), sexual intercourse with a partner who used injection drugs (42 percent), prostitution (30 percent), needle sharing (30 percent), receptive anal sex (19 percent), and having more than 100 sex partners (7 percent). After the analysis adjusted for age, education, race, HIV status, and addictive disorders, a lifetime occurrence of PTSD was associated with the practice of anal sex (odds ratio=1.7; 95 percent confidence interval=1.26 to 2.16; p.02) and prostitution (OR=1.56; 95% CI=1.17 to 1.95; p.03).HIV risk behaviors before incarceration were highly prevalent among the women in this study. Rates of PTSD, depression, and dysthymic disorder were also high. PTSD was associated with prostitution and receptive anal sex, and the disorder may contribute to high rates of risky sexual behavior. Targeted HIV risk reduction efforts among women prisoners should include evaluation for PTSD; conversely, women prisoners with a diagnosis of PTSD should be evaluated for prior HIV sexual risk behaviors.

Great strides have been achieved in recent years in the detection and treatment of major depressive disorder (MDD) in primary care settings. Little is known about the types or patients with MDD seen in primary care as compared with those seen in psychiatric office practice. Few studies have compared clinical outcomes after treatment with antidepressants in these two settings. In Argentina, the authors conducted an open-label treatment study of MDD patients in primary care (n = 469) and psychiatric office practice (n = 299). The patients were compared on baseline sociodemographic and clinical variables. These same patients were treated with sertraline 50-100 mg per day for 8 weeks. At baseline, the patients in psychiatric office practice were younger, more likely to abuse alcohol, less likely to have comorbid medical disorders, and more likely to have failed a prior treatment for depression during the current episode. The two groups did not differ significantly on depression severity or in depressive symptom profile on the Hamilton Depression Rating Scale (Ham-D). After 8 weeks of treatment, mean Ham-D scores were reduced comparably in both groups, from about 25 to about 10. Rates of adverse events were 14%-29%, depending on the follow-up interval. Adherence with treatment was high in both groups (over 95%). The patients in primary care and psychiatry office practice are similar in several ways. Significant reductions in depressive symptoms are possible in both settings, in large numbers of patients, by using doses of sertraline in the 50-100 mg range.

Research into many brain diseases, including stroke, Alzheimer’s disease, Parkinson’s disease, epilepsy, Huntington’s disease, and AIDS, has shown significant associations between these conditions and the presence of depressive disturbances. These associations are important for a variety of reasons. First, the occurrence of depression in neurologic disease is a natural experiment whose study continues to shed light on our understanding of the role of the brain in depressive illnesses. Second, the co-occurrence of depression and neurologic disease magnifies morbidity. Third, treatment of depression in neurologic disease may greatly improve prognosis. Perhaps the most interesting issue regarding the association between depression and neurologic disease is whether depression is caused by neurologic disease. Two general types of causal links should be distinguished. In the first, depression arises as a psychological reaction to the impairments or social disruption produced by the neurologic disease, in the same way that depression might arise in any individual faced with the adversities produced by a serious disease. In the second, depression is a specific symptom of the neurologic disease and is intimately tied to the pathophysiology of the disease. The relationship between stroke and depression has received sufficient investigation to make it a suitable model in discussing such potential causal relationships. In this article we review research on depression and stroke to illustrate how to approach causal links between neurologic disease and mental syndromes. Our major conclusion is that stroke lesions, under certain circumstances, cause depression through a direct but unknown pathophysiologic process.

Summary Major depression and mania have increased prevalence in HIV-infected patients, particularb in clinical settings and at later stages of disease. Varied rates of major depression have been reported but dzzerences in definition, methods of study, and population may partly explain these dafferences. We describe the clinical characteristics, assessment and treatment of mood disorders in HIV-infected patients, with emphasis on aspects specific to the setting of HIV infection. Diagnosis and treatment are complicated by medical complexity, stigma and psychosocial stress. Treatment is associated with clinical improvement. Mood disorders are associated with impulsivity, substance abuse, hopelessness, and demoralization, all of which may increase risk for HIV infection. Also, HIV-associated subcortical damage may be a risk factor for mood disorders, which are increased in late stage HIV infection. We discuss the data supporting the thesis that both of these factors may be at work in producing the high rates of mood disorders seen, and speculate that aggressive treatment of mood disorders may improve outcome and risk behaviors in HIV-infected patients.

The study sought to determine the effectiveness of a model program of psychiatric care for human immunodeficiency virus (HIV)-infected patients. This was a cohort study of 126 HIV-positive outpatients referred for psychiatric evaluation and treatment (average follow up of 14 months) in a HIV-dedicated primary-care outpatient clinic in the inner city. A global outcome measure (encompassing symptom relief, functioning, and HIV-risk behaviors), and a measure of abstinence from alcohol and illicit substances were used. Fifty percent of patients improved, with 19% "nearly well" at follow-up. Abstinence was achieved 48% of the time. Good compliance with treatment and the absence of injection drug use were the primary predictors of good outcomes. Of the compliant patients, 94% improved, with 45.7% being nearly well. Psychiatric treatment of HIV-infected patients is effective when located in the HIV primary-care setting and administered by a multidisciplinary team under the direction of a psychiatrist, using evidence-based interventions.

Patients with chronic pain present a spectrum of complexity that can be overwhelming for the individual practitioner. These patients require thoughtful care and a comprehensive treatment plan. This complexity should be acknowledged, not avoided, and the patient should be engaged, not shunned. A practical approach will assist in developing expertise and proceeding empathically. The presence of a superimposed personality disorder significantly increases the difficulty of caring for these patients. Studies investigating the prevalence of borderline personality disorder in patients with chronic pain averaged 30 %, highlighting the importance of being able to effectively treat this patient population. Appropriate management of these patients should focus on a collaboration to practice productive behaviors despite intense emotional distress. Longitudinal research provides a foundation for an optimistic prognosis that can be enhanced with this rehabilitative approach.