Lesson 6. Screening for Mental Health Conditions

In the United States, people with HIV have a high prevalence of mental health conditions. This curriculum uses the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) as the basis for screening for these conditions. In the DSM-5, all psychiatric conditions meeting the criteria for diagnosis are referred to as “mental disorders.” For the purposes of this curriculum, screening for substance use disorders has been separated from screening for the other mental illnesses frequently seen among people with HIV, and we refer to this latter group of illnesses as mental health conditions.  

People with HIV and mental health conditions often have comorbid substance use disorders.[1,2] Among the disorders described in the DSM-5, evidence suggests that major depression and substance use disorders have the strongest impact on the HIV care continuum, as they contribute to less safe sexual and injection drug-use practices, difficulty engaging in care along the entire HIV clinical care continuum, and problems with antiretroviral medication adherence.

People with mental health conditions are also overrepresented among those with poverty, homelessness, and incarceration. Mental health conditions, especially the most serious conditions (such as schizophrenia and bipolar disorder) and those combined with concomitant substance use disorders, often lead to a shortened lifespan in persons with HIV, even if they engage in HIV care and adhere to treatment.

Challenges in Evaluating Mental Health Conditions in Persons with HIV

Persons with HIV may also experience neurocognitive deficits. In particular, HIV-associated neuropsychiatric disorder (HAND) is an increasing concern for persons aging with HIV, and HAND often complicates the care of older persons (and some younger persons) with HIV. The aging of people with HIV and the neurocognitive problems associated with many of the comorbidities associated with HIV, such as substance use and chronic hepatitis C, contribute to the complexity of diagnosing and managing cognitive problems. In addition, severe depression and psychotic disorders are in and of themselves strongly associated with cognitive problems. Therefore, clinicians caring for individuals with HIV should be aware of the multitude of challenges implicit in the screening, diagnosis, and management of mental health conditions and neurocognitive deficits and should assist their patients in obtaining access to appropriate, integrated neuropsychiatric treatment. It is also important to bear in mind that persons with HIV may have more than one psychiatric or neuropsychiatric diagnosis.

Overview

This Topic Review will emphasize screening recommendations and tools for persons with HIV to identify common mental health conditions, including depression, bipolar disorders, common anxiety disorders, and post-traumatic stress disorder (PTSD), as well as neurocognitive disorders. Delirium in persons with HIV will not be addressed in this review, but delirium should always be ruled out prior to making a psychiatric diagnosis. A detailed discussion of definitions, diagnostic criteria, and treatment for particular DSM-5 conditions is beyond the scope of this review. Screening tools for Alcohol/Substance Use Disorders are addressed in the topic Substance Use Disorders.

Separate studies performed during different time periods have consistently shown that persons with HIV have relatively higher prevalence rates of various mental health conditions than are present among persons without HIV.[1,2,3,4,5] Several investigators have described a chronic neuroinflammatory state that exists in persons with HIV that may contribute to the high prevalence of depression among people with HIV.[6,7]

• Depression Symptoms Reported Medical Monitoring Project 2021 Cycle: This survey was conducted from June 2021 through May 2022, and it evaluated 3,995 persons with HIV for the presence of depression during the 2-week period prior to the interview.[8] Using DSM-IV criteria, 15.3% reported depression (8.6% had major depression and 6.7% had other depression); using criteria of a PHQ-8 score ≥10, 12.5% of participants had symptoms of moderate or severe depression (Figure 1).[8] In this same survey, 20.7% of persons with HIV reported anxiety, including 7.9% with severe anxiety (Figure 2).[8] Because the Medical Monitoring Project largely includes data only from persons with HIV who are receiving care, these data may not entirely reflect rates of depression and anxiety for all people with HIV.[8]
• PTSD Meta-Analysis in Women with HIV: In a meta-analysis of psychological trauma and post-traumatic stress disorder (PTSD) in women with HIV from the United States, investigators reported a PTSD rate of 30% among women with HIV, a rate approximately five times higher than among women without HIV.[9]

HIV Acquisition Risk

An extensive body of medical literature has documented an increased risk of HIV acquisition among individuals with mental health conditions.[10,11] For example, bipolar disorder may be associated with increased sexual activity, impaired judgment, risk-taking, substance use, and lack of stable housing—all factors that may increase the likelihood of HIV acquisition or transmission.[12,13,14] Social impairments associated with serious mental illness also increase HIV acquisition risk by interfering with the ability of an individual to maintain adherence with HIV preexposure prophylaxis (PrEP) and to negotiate condom use with casual or anonymous partners.[15] The following studies, when taken together, provide indirect support that mental illness is associated with HIV acquisition.

• NYC Psychiatric Inpatient Study (I): In a study conducted from December 1989 through July 1990, HIV testing was performed on all persons admitted to an acute psychiatric unit in Manhattan and a large state hospital in Queens, and investigators identified an HIV prevalence of 5.5% (25 of 451) with an HIV prevalence of 11.1% among black individuals.[16]
• NYC Psychiatric Inpatient HIV Prevalence Study (II): A second larger study from New York City reported HIV testing data from persons aged 19-59 years who were admitted at two public psychiatric hospitals from November 1989 through July 1991.[17] The HIV prevalence was 5.2% (50 of 962), and the prevalence rates were similar among women (5.3%) and men (5.2%).[17]
• Four-State Psychiatry Care HIV Prevalence Study: In this 4-state study, testing for HIV, hepatitis C, and hepatitis B was performed on adults aged 18 to 60 years undergoing inpatient or outpatient treatment in Connecticut, Maryland, New Hampshire, or North Carolina between June 1997 and December 1998.[14] The overall HIV seroprevalence rate was 2.7% (25 of 931), a rate at least 8 times the rate of the general United States population.[14]
• Global HIV Prevalence in Persons with Serious Mental Illness: This was a large meta-analysis of articles published between January 1, 1980, and January 1, 2015, related to HIV prevalence in persons with psychiatric conditions. This analysis included multiple global regions, but when analyzing the subset of 21 studies from North America, investigators found an HIV prevalence of 6.0% in this patient population.[10]
• Multisite HIV Prevalence Study in Mental Health Care Settings: A separate multisite cross-sectional study conducted in Philadelphia and Baltimore from January 2009 to August 2011 found an HIV prevalence of 4.8% (51 of 1061) among persons seen in different types of mental health care settings (university-based inpatient psychiatric units, intensive case-management programs, and community mental health centers).[18]
• Duke Psychiatric Outpatient HIV Prevalence Study: In a retrospective review at Duke University, HIV was present in 1.2% of the psychiatric patients seen in the outpatient setting, a prevalence rate approximately 4 times the rate of HIV in the general population in the United States (Figure 3).[19]

HIV Transmission Risk

Mental health conditions may increase HIV transmission risk through less medication adherence and increased sexual activity, often in the context of substance use.[20] Since persons with HIV who regularly take antiretroviral therapy and consistently maintain suppressed HIV RNA levels do not transmit HIV to sex partners, any factor that negatively influences antiretroviral adherence can interfere with this antiretroviral medication-related transmission benefit.[21] Major depression has been linked to increased rates of nonadherence to antiretroviral therapy, thus raising the likelihood of HIV transmission to partners.[22,23,24] In addition, anxiety, depression, and bipolar disorder have all been linked to increased sexual activity.[25,26,27] Treatment for mental health conditions, including treatment of substance use disorders, should be part of the overall efforts to reduce HIV transmission.[28,29,30] A Duke University psychiatry group has generated a conceptual model outlining the impact of mental health treatment on HIV transmission risk behavior in persons with HIV (Figure 4).[29]

Impact of Mental Health Conditions on the HIV Continuum of Care

The presence of untreated mental health conditions in persons with HIV correlates with decreased initiation of antiretroviral therapy, reduced medication adherence, and lower rates of viral suppression, all of which have significant implications for individual health.[31] Studies have established a relationship between reduced adherence with antiretroviral therapy and symptoms of depression, post-traumatic stress disorder (especially in those patients with concomitant depression), and bipolar disorder.[23,27,32,33] Post-traumatic stress disorder has also been shown to predict increased HIV symptomatology among both men and women with HIV, high rates of emergency room utilization, and increased HIV-related morbidity.[34,35]

impact of Mental Health Conditions on Morbidity and Survival

Mental health conditions have been shown to predict adverse outcomes in some groups of individuals with HIV who have a psychiatric condition. In particular, untreated depression significantly worsens adherence to antiretroviral medication, decreases the likelihood of full virologic suppression or CD4 cell recovery, and appears to increase the risk of disease progression and death.[36] Among individuals with HIV, those with mental health conditions experience increased morbidity and mortality when compared to comparable people who do not have these conditions.[37] Certain health problems are inherently increased in general with mental health conditions, such as the well-established association of major depression with heart disease. In addition, some psychotropic medications have the unfortunate side effect of weight gain, contributing to obesity and metabolic syndrome. Further, several studies have shown that anxiety and depression in people with HIV are associated with a decline in cognitive functioning, particularly in learning and memory.[38,39]

Among persons with HIV who have mental health conditions, treatment can improve psychiatric symptoms as well as improve adherence to antiretroviral therapy and overall HIV outcomes.[40] In some patients, the diagnosis of a mental health condition may facilitate closer monitoring and medical scrutiny, which fosters engagement in care and improved adherence rates. The following studies highlight evidence that shows addressing mental health care can have a major favorable impact on HIV outcomes.

• Women’s Interagency HIV Study (WIHS): In the Women’s Interagency HIV Study (WIHS), researchers analyzed the impact of depression on utilization of antiretroviral therapy in a total of 1,668 women with HIV who were enrolled in the WIHS at 6 sites nationwide between April 1, 1996, and September 30, 1998.[41] The analysis demonstrated that individuals who used mental health services had a 20% increase in the adjusted odds of utilizing antiretroviral therapy compared to those who did not access mental health services.[41]
• Kaiser/Group Health HMO Study: In a retrospective cohort study of 3,559 persons with HIV and depression who were enrolled in the Kaiser Permanente and Group Health Cooperative Health Maintenance Organizations (HMOs) in an 8-state region in the period January 2000 through December 2003, investigators analyzed the impact of depression and treatment of depression on HIV outcomes.[42] Among individuals with depression, rates of virologic suppression were lower, but those treated with selective serotonin reuptake inhibitors (SSRIs) had better adherence to antiretroviral therapy, improved virologic suppression, and a greater rise in CD4 cell count compared to their counterparts who did not receive SSRI treatment.[42]
• HIV Research Network (HIVRN): In a large, retrospective analysis of 4,989 persons with HIV who were receiving outpatient treatment during 2000 through 2005 at 5 sites affiliated with the HIV Research Network, investigators reported individuals with a psychiatric diagnosis who had six or more mental health visits in a year were significantly less likely to discontinue antiretroviral therapy compared with individuals with no mental health visits.[43]
• Atlanta Metropolitan Study: In this study, investigators followed 324 persons with HIV (on antiretroviral therapy) across 3 months time within during the study period of March 2005 to October 2008, with the goal of analyzing the impact of adherence to psychotropic medications on both depressive symptoms and antiretroviral adherence.[40] Overall, 33% (106 of 324) of those followed were also prescribed at least one psychiatric medication.[40] The investigators reported depression was associated with lower antiretroviral adherence, but adherence to psychiatric medications, regardless of medication class, increased antiretroviral adherence.[40]

• UAB Project CONNECT: In a retrospective analysis of 743 people with HIV who were seen at the University of Alabama at Birmingham (UAB) and enrolled in the Client-Oriented New Patient Navigation to Encourage Connection to Treatment (CONNECT) project between January 1, 2007, and December 31, 2013, investigators reported persons who received mental health services were more likely to be retained in primary care at 12 months relative to those who did not receive mental health services during their first year of care.[44]

Estimates of Neurocognitive Disorders in Persons with HIV

Cognitive disorders are widespread in the general population, with prevalence estimated to be 5 to 7% in most parts of the world; age is the major predictive factor for the development of dementia, and the prevalence of dementia nearly doubles every 10 years after age 60.[45] Overall, adults with HIV have poorer cognitive performance compared with those without HIV.[3,46,47] The prevalence of HIV-associated neurocognitive disorders (HAND) is estimated to be in the range of 25 to 50%.[46,48,49]

Factors Associated with Neurocognitive Decline in Persons with HIV

In persons with HIV, older age has been identified as a strong predictor of neurocognitive decline; other factors associated with neurocognitive decline include low nadir CD4 count, detectable plasma HIV RNA levels, previous central nervous system (CNS) injury, and comorbid conditions, such as hypertension, insulin resistance, viral hepatitis, and substance use disorder.[3,46,50] In addition, major depression, another common comorbid condition in persons with HIV, carries a significant burden of cognitive impairment that is reversible in part with the treatment of depression.[51,52] Among individuals with cognitive impairment and suppressed HIV RNA levels, intensification of antiretroviral therapy does not improve the cognitive impairment.[53]

HIV-Associated Neurocognitive Disorder (HAND)

The term HIV-associated neurocognitive disorder (HAND) is used to describe the spectrum of neurocognitive dysfunction that includes (1) asymptomatic neurocognitive impairment, (2) mild neurocognitive disorder, and (3) HIV-associated dementia.[54] These three conditions have been classified based on criteria established by consensus research definitions, referred to as the Frascati Criteria, and are not readily applied to clinical settings.[55]

• Asymptomatic Neurocognitive Impairment: This refers to mild neuropsychological impairment established by testing (rather than patient symptoms) in at least two ability domains that is not attributable to comorbid conditions.
• HIV-Associated Mild Neurocognitive Disorder: This disorder is defined by mild neuropsychological impairment in at least two domains not attributable to comorbid conditions plus at least mild interference in activities in daily functioning.
• HIV-Associated Dementia: This type of dementia is characterized by neuropsychological impairment of at least moderate severity and major functional decline in day-to-day functioning.

The Multicohort AIDS Study (a prospective study with gay and bisexual men) found that asymptomatic neurocognitive impairment doubles the risk of developing symptomatic HAND compared to a diagnosis of normal cognition.[48] In this study, only 2% of participants met the criteria for HIV-associated dementia, which is a significant drop from the 10 to 15% prevalence of HIV-associated dementia prior to the availability of effective antiretroviral therapy.[46] By contrast, the prevalence of milder forms of HAND has not declined despite effective antiretroviral therapy, though the study results are complicated by a CD4 nadir below 200 cells/mm³ in 70% of the participants. In addition to low nadir CD4 count, other risk factors linked to poor neurocognitive performance include increasing age, previous CNS injury, detectable HIV RNA, and comorbidities such as hypertension, viral hepatitis, substance use disorder, and depression.[46,50]

Differential Diagnosis of Neurocognitive Impairment

Although HAND describes a spectrum of neurocognitive impairment from mild to severe, it is important to recognize that persons with HIV continue to be at risk for other causes of neurocognitive decline, including cerebrovascular disease, severe psychiatric disorders, Alzheimer’s disease, metabolic disorders (such as hypothyroidism), alcohol and drug use disorders, side effects of psychotropic drugs, neurotoxicity related to certain antiretroviral medications, previous or current central nervous system opportunistic infections (and their sequelae), or other neurological diseases.[3,56,57,58,59] Treatable causes of neurocognitive disorders, such as depression, thyroid disease, B12 deficiency, syphilis, an opportunistic infection, and tumors should be identified and addressed.

HIV-Associated Brain Injury (HABI)

In 2023, an International HIV-Cognition Working Group issued a Consensus Statement that outlined recommendations for a new approach to cognitive impairment and causes of brain injury in people with HIV.[60] This working group has proposed a shift from using the HAND concept to an emphasis on conceptualizing brain injury in people with HIV as either (1) injury directly caused by HIV (HIV-associated brain injury [HABI]) or (2) injury from causes that are not directly caused by HIV (e.g., cerebrovascular disease, traumatic brain injury, neurodegenerative disorders).[60] In this context, HABI is subdivided based on whether plasma HIV RNA levels are suppressed or not suppressed.[60] Further, for individuals with suppressed plasma HIV RNA levels and evidence of brain injury, the working group characterized the brain injury as legacy (inactive brain injury from pretreatment damage) or active (ongoing brain injury leading to clinical and/or radiological progression).[60] The HIV-Cognition Working Group provided six main recommendations that summarize a new diagnostic approach to cognitive impairment in people with HIV (Table 1).[60]

History of Mental Health Screening Tools

In the early 1990s, Drs. Robert Spitzer, Janet B.W. Williams, Kurt Kroenke, and coworkers developed the 26-item Primary Care Evaluation of Mental Disorders (PRIME-MD) patient questionnaire as a screening tool for five of the most common psychiatric disorders: (1) depression, (2) anxiety, (3) somatoform disorders, (4) alcohol use disorder, and (5) eating disorders.[61] Although the PRIME-MD emerged as a groundbreaking mental health screening tool, its utility in clinical practice settings has been limited by the long administration time required by the clinician to complete the 26-item survey. These same investigators subsequently developed and validated a self-administered form of the PRIME-MD known as the Patent Health Questionnaire (PHQ).[62] The development of the PHQ led to shorter, more practical screening tools, such as the PHQ-9 screening tool for depression and the Generalized Anxiety Disorder 7 (GAD-7) screening tool. See the screening tools for Mental Disorders Screening category in the Tools & Calculators section of this website.

Barriers to Usefulness of Screening Tools

The primary limitation of screening tools for mental health conditions is the low rates of further diagnostic evaluation and linkage to and retention in mental health care that follows the initial screening. This problem has been well demonstrated with depression screening tools.[63,64] Barriers to treatment have led to a number of new team-based models for delivering mental health services within primary care; studies of these new models are promising, but they are not often conducted in settings where HIV care is delivered.[65] Although people with schizophrenia and other psychotic disorders have an increased risk of acquiring HIV, simple and reliable screening tools for these conditions are not available. Asking patients about prior psychiatric diagnoses, the use of psychotropic medications, and a history of psychiatric hospitalization is helpful in detecting these serious mental health conditions.

Ideal Aspects of Screening Tools in Primary Care

Practical screening tools for use in the primary care setting should be brief, easily scored, free, evidence-based, and accessible to a range of providers without specific training. In addition, screening tests should be limited to conditions for which there is an available, effective treatment that can directly target the disease and improve prognosis and outcomes.[66] Most of the common mental health conditions seen among people with HIV have effective treatments. An ideal screening test for a mental health condition will accurately identify individuals with the clinical condition of interest without diagnosing individuals who do not have the condition. This is referred to as the sensitivity (probability of a test being positive when illness is present) and specificity (the probability of a test being negative when illness is absent) of a screening test. In addition, the test should ideally identify persons with the condition and simultaneously not falsely categorize people without the condition as having the condition; this is referred to as the positive predictive value. 

Follow-Up for a Positive Screen

A positive screen for a mental health condition usually needs to be followed by a further clinical diagnostic evaluation to clarify that the condition crosses the threshold for a true mental health condition. Unfortunately, there are no biological tests that can be conducted in clinical care settings to clarify the presence of the vast majority of mental health conditions. The diagnostic accuracy of the screening test can be improved by testing for medical conditions that can cause delirium and dementia and screening for the presence of substance use disorder with alcohol and/or other drugs. Several screening tools for the most common mental health conditions encountered in primary care are described below, with links provided to the screening tool.

In June 2023, the United States Preventive Services Task Force (USPSTF) updated the screening recommendation for Depression and Suicide Risk in Adults (including women who are pregnant or postpartum), providing a Grade B recommendation for screening for major depression and a Grade I recommendation for suicide risk screening.[67] The USPSTF recommendations state, “It is important that persons who screen positive are evaluated further for diagnosis and, if appropriate, are provided or referred for evidence-based care.”[67] The HIVMA/IDSA Primary Care Guidance recommends screening people with HIV for depression at least annually and more frequently if needed.[68]

Patient Health Questionnaire-9 (PHQ-9)

The Patient Health Questionnaire-9 (PHQ-9) can be self-administered or administered by a health professional. The questionnaire scores each of the 9 DSM-5 criteria in the range of 0 (not at all) to 3 (nearly every day) for items in the survey during the most recent 2 weeks. The PHQ-9 was designed to serve as a multipurpose instrument tool for screening, diagnosing, monitoring, and measuring the severity of depression.[69] The PHQ-9 has also been validated across diverse patient populations, including African Americans, Chinese Americans, Latinos, and non-Hispanic whites.[70]

• Interpretation: The PHQ-9 score ranges from 0 to 27, with higher scores correlating with a greater likelihood of major depression (Figure 5).[69] In addition, a cumulative score of 10 points or higher has 88% sensitivity and specificity for major depression. The following PHQ-9 score ranges have been shown to correlate with different degrees of depression: 5 to 9 (mild), 10 to 14 (moderate), 15 to 19 (moderately severe), and 20 to 27 (severe).[69] For persons who have a score of 1 or higher on any question, an additional tenth question is asked that evaluates how these problems impact function at home, at work, and with others. Based on both clinical practice and a review of the literature, a PHQ-9 score of 10 or higher is often used as the basis for referring individuals for further assessment of depression.[71] This further evaluation is essential because a PHQ-9 score of 10 or greater substantially overestimates the prevalence of major depression.[72]
• Recommendation: Individuals who reach the threshold for a positive screen (a score of 10 or higher) should ideally be offered a full diagnostic interview using standard diagnostic criteria from the DSM-5.[73] If prompt further diagnostic evaluation is not available, the primary care clinician should use good clinical judgment, taking into account the duration and severity of the depression, its impact on functioning, and the individual’s treatment preferences. Moderately severe depression or severe depression warrants treatment using antidepressants, psychotherapy, and/or a combination of both. In addition, any positive response to question 9 (presence and duration of suicide ideation) warrants immediate further evaluation to determine if there is an imminent risk of self-harm. Suicide screening instruments, including the PHQ-9, have not been shown to significantly predict near-term outcomes, so additional risk stratification may be necessary.[74]

Patient Health Questionnaire-2 (PHQ-2)

The Patient Health Questionnaire-2 (PHQ-2) is a 2-item, validated screening tool that uses the first two questions of the PHQ-9 that ask about the frequency of depressed mood and anhedonia (the first two DSM-5 criteria for diagnosing major depression).[75] The PHQ-2 focuses the time frame to the past 2 weeks and grades answers on a 4-point scale.

• Interpretation: The PHQ-2 score ranges from 0 to 6. Using a cutoff score of 3, the PHQ-2 has a sensitivity of 83% and specificity of 90% for major depressive disorder. In one study, investigators concluded a cutoff score of 3 was the optimal cut point for screening purposes, with the qualification that moving the cut point to 2 would enhance sensitivity and moving to 4 would increase specificity (Figure 6).[75]
• Recommendation: The PHQ-2 functions as a brief, practical, first-step screening tool intended to identify individuals who require additional evaluation with another instrument, such as the PHQ-9, or a direct diagnostic psychiatric interview.[76] The PHQ-2 should not be used as a final diagnostic tool for depression.

2-Item PRIME-MD

The 2-item PRIME-MD, based on the 27-item PRIME-MD, is less commonly used but remains an option for screening for depression.[77,78] A positive screening result, answering yes to either one or both of the screening questions, requires additional evaluation with the PHQ-9 or a direct psychiatric interview that uses diagnostic criteria from the DSM-5.[73]

Hospital Anxiety and Depression Scale (HADS)

The Hospital Anxiety and Depression Scale (HADS), which was developed in 1983 to assess anxiety disorders and depression among patients attending hospital-associated clinics that were not psychiatric clinics, is another option for anxiety and depression screening.[79,80] Individuals who screen positive with a score of at least 8 points should be referred for a full diagnostic interview that uses diagnostic criteria from the DSM-5. Compared to several other screening tools, the HADS is not as useful in primary care settings.[81] People who reach the threshold for a positive score should be referred for a full diagnostic interview that uses diagnostic criteria from the DSM-5.

Generalized anxiety disorder (GAD) and panic disorder are two of the most common anxiety disorders in the United States. In people with HIV, treatment of these disorders has been shown to improve patient outcomes.[82] In June 2023, the United States Preventive Services Task Force (USPSTF) issued screening recommendations for Anxiety Disorders in Adults (including pregnant and postpartum women), providing a Grade B recommendation for those younger than 65 years of age and an I recommendation for those 65 years of age and older.[83] The USPSTF recommendations state, “It is important that persons who screen positive are evaluated further for diagnosis and, if appropriate, are provided or referred for evidence-based care.”[83] The HIVMA/IDSA Primary Care Guidance does not have any recommendations regarding screening for anxiety in persons with HIV[68] 

Generalized Anxiety Disorder-7 (GAD-7)

The 7-item Generalized Anxiety Disorder-7 (GAD-7) anxiety scale is a brief, self-administered questionnaire that has been validated in the general population to identify patients with probable generalized anxiety disorder.[84,85,86] The questionnaire includes questions about anxiety symptoms occurring in the past 2 weeks.

• Interpretation: The GAD-7 scores can range from 0 to 21. A major study identified a cut-point score of 10 as having the optimized sensitivity (89%) and specificity (82%) for diagnosing generalized anxiety disorder (Figure 7).[86] Score categories correlate with different levels of anxiety: 0-4 (minimal), 5 to 9 (mild), 10 to 14 (moderate), and 15 to 19 (severe). A more recent meta-analysis suggested using a cutoff score of 8 to optimize sensitivity without compromising specificity.[87]
• Recommendation: Individuals who meet the threshold for a positive GAD-7 screen (a score of 8 or above) should ideally have a complete diagnostic evaluation.

Patient Health Questionnaire for Panic Disorder (PHQ-PD)

This 5-item screening instrument is one subset of questions (questions 3a-d and questions 4a-k) derived from the longer Patient Health Questionnaire (PHQ), which itself is a short, self-reported instrument derived from a physician-administered PRIME-MD interview. The PHQ-PD (also called the panic module of the PHQ) has been found to be a valid screening instrument with a sensitivity of 44 to 66% and a specificity of 87 to 95%, depending on the scoring algorithm that is applied.[88] Using a single screening question taken from the PHQ-PD module (e.g., question 3a: “In the last 4 weeks, have you had an anxiety attack—suddenly feeling fear or panic?”) improves sensitivity to 71% but drops specificity to 84%.

• Interpretation: A positive score on the original panic module is indicated with a positive (yes) answer on all four questions 3a-d plus a positive (yes) answer on at least four items from questions 4a-k. Modified versions of the test improve sensitivity by requiring only 2 or 3 positive answers for questions 3a-d. The most sensitive version of the panic module screener is the single screening question 3a; a yes answer to this single question is considered a positive screen.
• Recommendation: Many experts recommend using the single screening question (question 3a) since it has better psychometric properties than the full PHQ-PD algorithm.[88] Moreover, because primary care settings do not usually screen for panic disorder, adding only one question minimizes any additional burden to screening procedures already in place. Individuals who screen positive require follow-up with a formal diagnostic procedure.

There is limited evidence to support screening the civilian primary care population for post-traumatic stress disorder, and the United States Preventive Services Task Force does not address PTSD screening. In contrast, other organizations, including the National Institute of Health Care and Excellence in the United Kingdom (NICE-UK), recommend screening for PTSD when there is known exposure to a traumatic stressor.[89] Multiple PTSD screening instruments are available, including the 5-item Primary Care PTSD Screen from DSM-5 (PC-PTSD-5), the 17-item PTSD Checklist, the 4-item Startle-Physiologic Arousal-Anger-Numbness (SPAN), the 7-item Breslau’s scale, the 10-item Trauma Screening Questionnaire, and the Single-Item PTSD Screener.[89,90,91] Among these screening tools, the PC-PTSD-5 test (five items) appears to be the best single screening test for PTSD for use in primary care.[90]

Primary Care Post-Traumatic Stress Disorder (PC-PTSD)

The Primary Care PTSD for DSM-5 (PC-PTSD-5) screening test is a 5-item scale that includes questions about symptoms unique to PTSD (re-experiencing, avoidance, numbness, hyperarousal, and feelings of guilt or blame).[91] One study found that the previously used 4-item PC-PTSD was more effective when used in combination with the General Health Questionnaire-12 (GHQ-12), which is a set of 12 questions used to screen for nonpsychotic psychiatric disorders and graded on a 4-point response scale.[92]

• Interpretation: Different studies recommend different cutoff scores for a positive screen. A study involving 398 Veterans patients at a primary care clinic found a score of 3 correlated with 95% sensitivity and 85% specificity for the diagnosis of PTSD (Figure 8).[90,91] Another large study that used data extracted from clinical databases for Veterans Affairs primary care patients used a score of 2 or greater as the cutoff for a positive PC-PTSD screen.
• Recommendation: Individuals who screen positive on the PC-PTSD screening test qualify for additional evaluation from the primary care provider or a mental health practitioner that includes an interview evaluating PTSD criteria from the DSM-5.

Bipolar disorder encompasses a spectrum of clinical disorders (bipolar I disorder, bipolar II disorder, and cyclothymic disorder) consisting of episodes of manic, hypomanic, and depressive symptoms. The heterogeneous presentation of bipolar disorder can make it difficult to detect this disorder through screening, and lifetime prevalence estimates of bipolar disorder vary widely across studies.[93] The National Comorbidity Survey estimates that the lifetime and 12-month prevalence for bipolar I disorder is 1.0% and 0.6%, respectively; for bipolar II disorder, these numbers are 1.1% and 0.8%.[94] There are no formal recommendations for screening for bipolar disorder; however, some experts recommend that primary care physicians implement selective screening for bipolar disorder in patients with known depression, anxiety, or substance use disorders.[93]

Mood Disorders Questionnaire (MDQ)

The Mood Disorders Questionnaire (MDQ) can be used to screen for a lifetime history of mania or hypomania. The MDQ consists of 13 yes or no questions based on DSM-5 criteria for bipolar disorder with two additional items to assess the frequency and severity of yes responses. In primary care, evaluation of whether a person has bipolar disorder arises most frequently in the context of beginning an antidepressant medication, since these medications can precipitate mania in vulnerable individuals. The MDQ is not a practical screening tool for most primary care clinicians, primarily because of the need to ask so many questions. Accordingly, some clinicians may find that asking a few pointed questions during history taking can be useful in ruling out a history of mania: (1) “Have you ever been told that you have manic-depressive illness or bipolar disorder?” and (2) “Has there ever been a period of time when you were not your usual self, and you had much more energy than usual?” These questions parallel two of the items on the MDQ. Any yes answer would then lead to further inquiry.[95,96]

• Interpretation: In the primary care setting, a score of 7 on the MDQ has a sensitivity of 43% and a specificity of 95% for detecting any type of bipolar disorder. In the mental health setting, diagnostic characteristics are better overall: for a score of 7, sensitivity is 81% and specificity is 85% (Figure 9).[96]
• Recommendation: Based on data showing low sensitivity but high specificity (and high negative predictive value), bipolar disorder screening tools, such as the MDQ, may be utilized most appropriately to rule out bipolar disorder in patients presenting with depression, rather than as a general screening tool.[97,98]

Recommendations to Screen for Neurocognitive Disorders

The United States Preventive Services Task Force (USPSTF) has found insufficient evidence to recommend for or against screening for cognitive impairment in older adults in the general population in the absence of known impairments.[99] Considering that as many as 50% of persons with HIV have some form of HIV-associated neurocognitive disorder, most experts recommend that persons with HIV should ideally have a baseline neurocognitive assessment, with follow-up screening every 6 to 12 months for individuals at high risk for HAND and every 12 to 24 months in persons at lower risk.[100] From a practical standpoint, however, this recommendation is often not implemented because existing clinical screens do not perform well in identifying milder forms of HAND. Therefore, identifying and developing practical screening tools for individuals with HIV that can detect milder forms of HAND and distinguish among the different HAND disorders is essential.

Screening Tools for Neurocognitive Disorders

Among the tools that are currently available, no consensus exists on which screening tool to use. The primary care literature offers four brief screening tools that are not specific to the diagnosis of HAND but are validated for general use in the primary care setting (Mini-Mental State Examination, General Practitioner Assessment of Cognition, Memory Impairment Screen, and Mini-Cognitive Assessment Instrument). The American Academy of Neurology acknowledged in its 2001 report on early detection of neurocognitive impairment that more research is needed to help clinicians differentiate among available screening instruments.[101,102,103] Several HIV-specific neurocognitive screening tools have been developed, but a consensus panel of experts on HIV neurocognitive disorders has concluded no single screening test is appropriate in all clinical situations—the choice of test may vary with patient population, provider experience and preference, cost, and time—and further acknowledges that all the available tools are less sensitive for detecting milder forms of cognitive impairment.[100] At the present time, a comprehensive neuropsychological assessment remains the gold standard for diagnosing HIV-associated neurocognitive disorders.

General Population Neurocognitive Screening Tools

Mini-Mental State Exam (MMSE)

The MMSE is among the oldest screening tools for cognitive impairment. The MMSE, which takes approximately 5 to 10 minutes to administer, includes a series of questions that cover 7 cognitive domains: orientation, registration, attention and calculation, recall, language, and construction.[104,105] A score of 24 points or lower (out of a total of 30 points) represents cognitive impairment. Most experts agree the MMSE is a weak tool for diagnosing HAND.[106,107] Despite free available versions of the MMSE, Psychological Assessment Resources (PAR) now holds exclusive rights to the MMSE and claims that any use of the MMSE requires their permission and ordering through them. Due to poor performance in evaluating HAND in persons with HIV (and the logistical problems obtaining this test), we do not recommend using MMSE as a neurocognitive screening tool for HAND.

Mini-Cognitive Assessment Instrument (Mini-Cog)

The Mini-Cog is a test consisting of a three-word registration, followed by a clock-drawing test, and then followed by three-word recall.[108] Patients receive 0 to 3 points based on the number of items recalled, and 0 or 2 points for clock drawing (a correct clock should have all the numbers placed appropriately, with the hands pointing to the time designated by the examiner). A total score of 0 to 2 indicates dementia. The test has sensitivity ranging from 76 to 99% and specificity ranging from 73 to 93% across studies.[101,109] Because of its speed, accuracy, and the fact it does not require patient fluency in English, some primary care providers suggest using this test as the initial screen.[101] Again, the Mini-Cog is not specific to HAND.

The General Practitioner Assessment of Cognition (GPCOG)

The GPCOG consists of 6 initial questions involving registration and recall, time orientation, clock drawing, and historical questions.[110] A two-part version of the GPCOG with an additional 6 questions can be used if the examiner knows the patient well enough to validate the historical questions. A score of 9 or above is considered normal, and a score of 4 or lower indicates cognitive impairment. For patients scoring in the 5 to 8 range who have a longstanding relationship with their provider, the second part of the GPCOG asks providers questions about the patient’s current functional status compared to 5 years ago. Using a cutoff of 7 points for dementia, the sensitivity and specificity for the GPCOG is 82% and 70%, respectively; the two-part GPCOG increases the specificity to 83%.[101]

Memory Impairment Screen (MIS)

The MIS is a 4-minute, 4-item delayed, free, and cued recall test.[111] The patient is given a piece of paper with the names of four different items (an animal, vegetable, city, and musical instrument). The patient then counts from 1 to 20 and then back to 1; they are then asked to recall the names of the four items. A total of 2 points are given for items recalled without cueing, and 1 point is given for items recalled with cueing. As a screening tool for dementia, based on a cutoff score of 5, the sensitivity of the MIS is 86%, and the specificity is 91%.[101]

Montreal Cognitive Assessment (MOCA)

The MOCA is a free, online, validated instrument that is available in many languages to screen for mild cognitive impairments. The MOCA takes approximately 10 to 15 minutes to administer and consists of 30 items that measure function in 8 cognitive domains.[112] A score of 26 points or lower (out of a maximum of 30) indicates cognitive impairment. The MOCA has been found to be more sensitive than the Mini-Mental Status Exam (MMSE) at detecting mild cognitive impairment in the general population.[102,113] Among individuals with HIV, the MOCA has only moderate sensitivity and poor specificity for detecting mild cognitive impairment.[112]

HIV-Specific Neurocognitive Screening Tools

HIV Dementia Scale (HDS) and Modified HIV Dementia Scale (M-HDS)

The HIV Dementia Scale (HDS) is a test consisting of 4 items that address 4 cognitive domains: memory/recall, attention/learning, psychomotor functioning, and eye movements (visuoconstruction); the maximum score on the HDS is 16.[112,114,115] The HDS was originally developed in 1995 and found to be superior to the Mini-Mental Status Exam for identifying HIV-associated dementia. In one study, using an HDS cutoff score of 10 or less for identifying HIV dementia, the HDS performed with a sensitivity of 80%, specificity of 91%, and positive predictive value of 78%.[114] The HDS has been found to have inadequate sensitivity and specificity for detecting milder forms of cognitive impairment.[112,116] A modified version of the HDS (M-HDS) is a more practical screening tool for clinicians and non-neurologists.[117] The modified test eliminates the evaluation of antisaccadic eye movements, an examination deemed difficult for non-neurologists.

International HIV Dementia Scale (IHDS)

In 2005, the International HIV Dementia Scale (IHDS) was developed by Sacktor and colleagues and adopted for use in global settings to address culturally specific elements of the original HIV Dementia Scale and trouble administering the anti-saccadic errors test.[118,119] The IHDS test has three tasks that evaluate motor speed, psychomotor speed, and memory recall: timed finger tapping, timed alternating hand sequence test, and 4-item recall at 2 minutes.[119] The maximum score is 12 points.[119] Patients with a score of 10 or lower should undergo further evaluation for possible dementia.[119] A meta-analysis showed this test performed well when screening for dementia but had low accuracy for milder HAND conditions.[116]

European AIDS Clinical Society (EACS) Cognitive Screen

The European AIDS Clinical Society recommends initial screening for cognitive impairment using 3 questions related to memory loss, reasoning, and attention. The questions are graded as never, hardly ever, or yes, definitely; an answer of yes, definitely on at least one question is considered to be an abnormal screen.[4]

Integrating Screening into Primary Care

Models for integrating the evaluation and management of mental health conditions into the primary care setting have focused primarily on depressive disorders; key elements of this integrative approach are highlighted in the recent United States Preventive Services Task Force (USPSTF) recommendation that endorses routine screening for depression in the general adult population, including pregnant and postpartum women.[120] The USPSTF statement indicates that implementation of the screening recommendation is best realized through a collaborative model of multidisciplinary, team-based care developed by the Community Preventive Services Task Force. This model uses case managers to connect primary care providers, patients, and mental health providers with stated goals of increasing screening and evidence-based treatment as well as improving clinical and community support for patient engagement in self-management. In this model, providers are responsible for screening patients, initiating treatment, and ensuring proper referral, while the case managers provide patient education, tracking, and management of the treatment plan. 

Integrating Mental Health Screening in HIV Care Settings

Depression Treatment Cascade

Given the high prevalence of mental health conditions, particularly depression, among persons with HIV, collaborative care models that allow for mental health treatment within the HIV medical home are paramount.[121] A depression treatment cascade, mirroring the well-known HIV treatment cascade, has been published, and it highlights the attrition along the continuum from depression diagnosis to effective treatment; according to this cascade, 18% of individuals with HIV and depression are receiving any treatment for depression, 7% are receiving adequate treatment, and only 5% are in remission (Figure 10).[121] There is also interplay between the two cascades since depression is recognized to decrease engagement in HIV care and adherence to antiretroviral medication.[121]

Collaborative Care Models

Despite the recognized mental health treatment gap, there are limited data related to evidence-based strategies that can be integrated into HIV primary care. Some proposed solutions include co-located services and the use of embedded mental health providers. Just as the initiation of HIV care is more likely when diagnosis occurs at a site that offers co-located medical care, mental health treatment is also more likely when it is co-located within the familiar setting of a patient’s medical home.[122,123] Collaborative care models to link antiretroviral and antidepressant management have also been tested in clinical trials. One such collaborative model, termed measurement-based care, has reported improvement in depression among participants. Measurement-based care is a decision support model for integrating antidepressant management into routine HIV care, in which depression case managers use metrics to give HIV primary care clinicians antidepressant treatment recommendations.[121,124]

Limits of Collaborative Care Models

It is important to note that collaborative care models in primary care are targeted for people who have mild to moderate mental health conditions and may not be able to provide the full range of services needed by people with HIV who have serious mental health conditions, such as bipolar disorder, schizophrenia, and other psychotic conditions.

• Among adults in the United States, the prevalence of depression, anxiety, and PTSD is significantly higher among adults with HIV than in adults without HIV.
• There is an increased risk for HIV acquisition and HIV transmission associated with certain mental health conditions, and mental health conditions have been associated with decreased utilization of antiretroviral therapy and predict worse HIV disease outcomes.
• Practical screening tools for use in the primary care setting should be brief, easily scored, free, evidence-based, and accessible to a range of providers without requiring specific training.
• Screening tools for some of the most common mental health diagnoses encountered in primary care include 2-Item PRIME-MD, PHQ2, and PHQ-9 (depression); GAD-7 (generalized anxiety disorder) PHQ-PD (panic disorder); and PC-PTSD-5 (post-traumatic stress disorder). A positive result on any screening test requires confirmation with a formal diagnostic interview.
• HAND likely affects 50% of persons living with HIV, with older age representing the greatest risk factor. Additional risk factors for HAND include low nadir CD4 count, previous central nervous system injury, detectable plasma HIV RNA levels, and comorbidities such as hypertension, insulin resistance, viral hepatitis, depression, and substance use disorder.
• HAND is subdivided into three categories based on the severity of disease: (1) asymptomatic neurocognitive impairment, (2) mild neurocognitive disorder, and (3) HIV-associated dementia.
• Screening tools for neurocognitive disorders include, among others, the MMSE, Mini-Cog, GPCOG, MIS, MOCA, European AIDS Clinical Society Cognitive Screen, HIV Dementia Scale, and International HIV Dementia Scale.
• Neurocognitive disorders screening tools work best when screening for HIV-associated dementia and they do not reliably detect milder forms of HIV-associated neurocognitive disorders.
• Co-located services, the use of embedded mental health providers, collaborative care, and decision support tools may all help to integrate mental health care into HIV primary care and improve the HIV treatment cascade.
• Meeting the needs of people with both HIV and the most serious mental health conditions, such as bipolar disorder and schizophrenia, are not well addressed in the common models proposed for integrating primary and HIV care along with care for people with mild to moderate mental health conditions. There are also no simple and reliable clinical tools for screening for psychosis. Thus, these individuals remain a challenging population to manage in the HIV clinical care setting.