Michael B. Blank, PhD

This article provides an overview of the interface between HIV/AIDS infection and mental illness.

At the end of this CE activity, participants should be able to:

• Delineate the prevalence of HIV/AIDS in person with mental illness

• Identify the primary mental health comorbidities associated with HIV/AIDS

• Explain the role of substance abuse in the symptom to infection pathway

• Identify treatment interventions for persons with comorbid HIV/AIDS and mental illness

This continuing medical education activity is intended for psychiatrists, psychologists, primary care physicians, physician assistants, nurse practitioners, and other health care professionals who seek to improve their care for patients with mental health disorders.

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Michael B. Blank, PhD, reports that he has received support from the National Institutes of Health (NIH), National Institute of Mental Health, National Institute of Child Health and Human Development, National Institute of Allergy and Infectious Diseases (NIAID), CDC, and the American Psychological Association.

Karl Goodkin, MD, (peer/content reviewer) reports that he has received support from the NIH and NIAID and that he is a consultant for the American Academy of Neurology and the American Psychiatric Association.

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Every clinician who treats people with HIV/AIDS recognizes that co-occurring affective disorders (eg, major depression, bipolar disorder), substance abuse disorders, cognitive disorders, psychotic disorders, and/or anxiety disorders are also part of the picture. Often these patients have been excluded from randomized clinical trials for new drugs and other treatments. As a result, there has been a missed opportunity to provide informed guidance to clinicians who treat patients with these comorbidities.

Persons with mental illness are at increased risk for contracting and transmitting HIV. This increased risk is thought to be due to high rates of substance use, including injection drug use; risky sexual behavior; sexual victimization; and prostitution. A recent study found a 4-fold increase in HIV infections among persons receiving mental health care in a variety of treatment settings in Philadelphia and Baltimore.

 Individuals were tested for HIV in university-based inpatient psychiatric units (n = 288), where 5.9% were HIV-positive; in assertive community treatment programs (n = 273), where 5.1% were HIV-positive; and in community mental health centers (n = 501), where 4.0% were infected. HIV infection was associated with being African American, gay, or bisexual; with having hepatitis C virus co-infection; and with psychiatric symptom severity. The study suggests routine HIV testing in all inpatient and outpatient mental health treatment settings.

When mental illness markedly compromises adherence to HIV treatment regimens, public health is threatened: community viral load is increased, and treatment-resistant virus strains can develop. The person with mental illness may therefore serve as a vector of HIV transmission. There is a pressing need for improved continuity of care by detecting infections early, increasing access to HIV treatment, and reinforcing treatment adherence so that people can maintain undetectable viral loads.

Today, adverse outcomes from HIV infection are far from inevitable. People with mental illness and HIV infection who receive good quality health care can achieve adherence rates comparable to those in others. In fact, there is evidence that with appropriate supports, these patients can adhere to treatment and may be less likely to discontinue antiretroviral therapy (ART).

Risk factors associated with HIV infection among persons with mental illnesses mirror those in the general population and include unprotected sex and injection drug use. The estimated prevalence of HIV infection in patients with serious mental illness during the 1990s and early 2000s ranged from 1% to 23%.

 Prevalence estimates from these studies varied tremendously because of methodological differences in sampling, particularly the reliance on convenience samples of high-risk individuals in institutions or geographically restricted areas. Small sample sizes also compromised these estimates.

An analysis of claims linked to the New Jersey HIV/AIDS registry showed that 5.7% of patients with schizophrenia also had HIV infection.

 In another study, patients with schizophrenia spectrum disorder were 1.5 times as likely to have HIV infection, and those with major affective disorder were 3.8 times as likely.

 Administrative medical records from a national sample from the Veterans Administration (VA) also point to elevated rates of HIV infection in severely mentally ill patients.

Estimates based on true epidemiological samples are rare. Perhaps because of shortcomings in existing detection systems, these estimates are often limited in their ability to shed light on people with more severe psychotic illnesses. A recent study using the National Epidemiologic Survey on Alcohol and Related Conditions reported that men with HIV infection were significantly more likely to have a range of diagnoses, compared with their HIV-negative counterparts.

 The prevalence of 12-month psychiatric disorders was stratified by gender to examine the increase in risk of a psychiatric disorder as a function of the interaction between gender and HIV status. HIV-positive men were more likely to have a mood disorder, MDD/dysthymia, any anxiety disorder, and a personality disorder than men who did not have HIV infection. The same comparisons were not significant in women.

The prevalence of HIV infection with comorbid psychiatric disorders may be underestimated because of the likelihood that not all HIV diagnoses are captured. Those that are may not be reliably linked to confirmed HIV-positive tests within administrative databases. When a more direct case ascertainment strategy was used, HIV infection was observed in 10.1% of patients.

 These findings indicate some serious shortcomings in patient care, which suggests that persons with mental illness are likely underserved with regard to identification of HIV.

Relatively few guidelines have been developed for clinicians who treat persons with HIV infection and mental illness. These guidelines are listed in

. Note that the 2000 and 2010 guidelines from the American Psychiatric Association may already be outdated.

A web-based survey of members from the Organization of AIDS Psychiatry sought to identify common use of psychopharmacology.

 With a response rate of only 39% (n = 69), the findings should be interpreted with caution, but treatment trends were observed: first-line treatment for depression: escitalopram/citalopram; for psychosis and secondary mania: quetiapine; and for anxiety: clonazepam.

A national survey of members of the American Academy of HIV Medicine focused on the initiation of ART for patients with comorbid HIV infection and schizophrenia.

 The results showed that clinicians recognized the importance of recommending ART to patients as well as avoiding antiretroviral medications with known neuropsychiatric adverse effects. Such studies have led to an effort to develop biopsychosocial curricular components of residency training for psychiatrists.

Depression and other affective disorders are common comorbidities of all chronic illnesses including HIV infection, and they provide particular clinical challenges. They often interfere with adherence to ART as well as with other aspects of self-care, virologic and immunologic outcomes, and quality of life.

Depression is the most common psychiatric comorbidity with HIV infection.

A meta-analysis was undertaken to evaluate the relationship between depression and HIV medication adherence to determine the overall effect size and to examine potential methodological and measurement moderators.

 Depression was significantly associated with nonadherence; larger effects were found for studies that collected data via interviews versus self-administered questionnaires.

 Larger effect sizes were also found when depression was considered along a continuum of severity rather than as a dichotomous variable. No differences in effect sizes were found for cross-sectional versus longitudinal studies. Assessment for depression, even at subclinical levels, as well as treatments for depression should be included in all HIV behavioral interventions. 

 lists common treatments for depression in people with HIV infection.

The estimated prevalence of MDD among patients with HIV/AIDS ranges from 20% to 37%-more than 3 times the rate in the general population.

 Like other chronic and life-threatening illnesses, HIV/AIDS can be stressful to manage, and people who live with this infection are particularly vulnerable to depression and other affective disorders. The life-threatening nature of HIV infection itself may instigate fears of impending mortality. Moreover, the medical sequelae of HIV infection such as HIV-associated neurocognitive disorders, associated opportunistic infections, and the adverse effects of ART can mimic symptoms of depression (ie, fatigue, problems concentrating, somatic symptoms, decreased appetite/weight loss).

From a cognitive-behavioral perspective, these physical symptoms can be part of a cycle of continued depression. Other factors that might account for the high level of depression and other affective disorders are unique to HIV. Specifically, people with HIV/AIDS disproportionately belong to socially disadvantaged and marginalized populations who are already at risk for depression because of their racial, ethnic, or sexual minority status, poverty, current or prior substance use, sex work, and/or trauma.

Depression rates do not appear to decline with age in HIV-positive populations as they do in the general population. This is important because as many as one-quarter of all US adults who are HIV-positive are now aged 50 years or older. As people live longer as a result of medical advances, depression in a gradually aging HIV cohort will remain an issue that needs to be addressed clinically and accounted for in HIV research. While there is evidence that the presence of severe psychiatric illness can negatively affect HIV care-particularly medication adherence-studies also underline the importance of individualized assessment and the potential positive impact of good psychiatric and substance abuse care.

 used a mobile outreach van to recruit a probability sample of homeless and unstably housed men. Those who tested positive for HIV were screened for mental illnesses. Participants receiving ART were compared with those eligible for ART but not receiving it. Mental health treatment in the past 90 days significantly increased the likelihood of receiving ART. No significant impact on the odds of receiving ART was found for a current mental illness, but among those taking ART, mental illness was associated with a 6 times higher viral load. The authors concluded that providing psychiatric treatment to impoverished HIV-infected people could help optimize health outcomes.

Psychotherapeutic interventions may be well suited to address the psychosocial difficulties as well as the distress associated with HIV. Of note, telephone-based cognitive behavioral therapy (CBT) has emerged as a feasible, acceptable, and effective treatment for major depression. Himelhoch and colleagues

 developed a manualized telephone-based CBT intervention and compared it with face-to-face therapy among 34 low-income, urban-dwelling patients with HIV/AIDS. The primary outcome was reduced depression; medication adherence was the secondary outcome. No differences were found for reductions in depressive symptoms; however, better treatment adherence was seen in the telephone-based CBT group. This study suggests that telephone-based CBT may be an alternative to standard treatment.

A Brazilian study found a high incidence of bipolar disorder in patients with HIV/AIDS.

 Adults with HIV infection were assessed using the Mood Disorder Questionnaire: 13.2% (n = 26) of study participants screened positive for bipolar disorder, and the diagnosis was confirmed in 8.1% (n = 16). This represents almost a 4-fold higher prevalence than in the general population. Factors associated with bipolar diagnoses were sex with commercial sex workers, sex outside a primary relationship, alcohol use disorders, and illicit drug use. Not surprisingly, the most common psychiatric comorbidity among persons with bipolar disorder was substance abuse (61.5%).

A US study examined HIV transmission risk behavior among 63 people with HIV/AIDS comorbid with bipolar disorder, MDD, or no mood disorder; half also had a substance use disorder.

 Participants who had HIV/AIDS and bipolar disorder were more likely to report unprotected intercourse with HIV-negative partners and poorer adherence to ART. In multivariate models, bipolar disorder and substance-use disorder were independent predictors of both risk behaviors. Patients with bipolar disorder need to be carefully evaluated and referred to HIV prevention services to reduce HIV transmission risk behaviors.

As many as 16% to 36% of persons with HIV infection have anxiety disorders.

 The HIV Cost and Services Utilization Study showed that 16% of HIV-infected individuals met criteria for generalized anxiety disorder and that 10.5% met criteria for panic attacks.

 Adjustment disorder with anxious mood was the most common, followed by generalized anxiety disorder and panic disorder; anxiety disorders are also a common comorbidity with depression. Although SSRIs are effective for anxiety disorders, Vitiello and colleagues

 found that 63% of the medications prescribed for anxiety among HIV-infected individuals were benzodiazepines. That finding is of some concern because of the high rates of substance abuse among HIV-infected persons and the potential for abuse of benzodiazepines. Approaches to the treatment of anxiety comorbid with HIV infection are listed in 

Among persons who are HIV-positive, the rate of lifetime PTSD and the incidence of HIV-related PTSD were estimated to be 54% and 40%, respectively.

 However, these estimates should be interpreted with caution, since they are based on only 85 patients with recently diagnosed HIV infection who participated in a cross-sectional study of lifetime rates of PTSD and HIV-related PTSD. Although there seems to be a high co-occurrence of PTSD and its harmful effects in HIV-infected individuals, there is relatively little research on treating PTSD in this population. Prolonged exposure therapy is a well-supported psychotherapeutic treatment for PTSD and has demonstrated efficacy in a wide range of trauma populations. More research, however, is needed to see if it is effective in treating PTSD comorbid with HIV/AIDS.

HIV risk is complex in schizophrenia, in which the onset of the illness is typically in late adolescence and early adulthood in both men and women-during the same developmental period in which sexuality and sexual behaviors typically increase in importance and frequency. This dynamic combined with the increased vulnerability to abuse and exploitation of persons with schizophrenia spectrum disorder makes these persons particularly susceptible to contracting and transmitting HIV and other infectious diseases.

Antipsychotics are standard treatment for psychotic symptoms in people with HIV/AIDS. The atypicals are more effective and have fewer extrapyramidal effects than traditional antipsychotic medications, such as haloperidol or thioridazine. However, many of the atypical antipsychotics are associated with an increased risk of obesity and metabolic syndrome that can potentially lead to cardiovascular disease and diabetes. This situation is aggravated by the fact that ART has also been linked to an increased risk of metabolic syndrome. It may be advisable to use typical antipsychotic agents for people who are on ART. Specific, evidence-based treatment guidelines are needed, based on biological and behavioral studies of the treatment of schizophrenia spectrum disorders among individuals also in treatment for HIV/AIDS, to improve psychiatric, behavioral, and medical outcomes. 

 lists common treatments for comorbid schizophrenia and HIV.

The interaction between symptoms of mental illness, substance abuse, and HIV risk behaviors is complex and recursive. The symptom to infection pathway needs to be understood in the context of multiple environmental and behavioral factors. As with any life-threatening chronic illness, an HIV diagnosis often brings depression and anxiety with it. Furthermore, the virus itself has direct neurotoxic effects that can result in HIV-associated neurocognitive disorder-a complex syndrome characterized by a wide variety of neurological and performance deficits.

The severity of mental illness symptoms has been associated with a higher risk of HIV infection. In one study, baseline data on 228 HIV-positive and 281 HIV-negative participants from 2 clinical trials were used.

 Years to HIV diagnosis served as the primary endpoint. A Colorado Symptom Index (CSI) score of at least 30 was associated with a 47% increased risk of HIV infection (P < .01). This study established a basis for using CSI scores to identify a vulnerable subgroup within the community of persons with serious mental illness. Further studies might develop effective approaches to mitigate psychiatric symptoms in order to examine the impact on HIV-transmission risky behaviors. It seems probable that effective mental health treatment and substance abuse treatment will be effective HIV prevention.

There is compelling evidence that substance abuse profoundly raises the risk of HIV infection in people with mental illness. In a large sample of patients with schizophrenia spectrum disorders treated through the VA system, Himelhoch and colleagues

 found that schizophrenia and comorbid substance abuse markedly increased the risk of HIV infection. In the absence of substance use, persons with schizophrenia were at lower risk for HIV infection than the general VA population.

 had similar results. Using Medicaid claims, the researchers examined new HIV diagnoses among patients with serious mental illness. Logistic regression and Cox regression revealed that 24% of persons with a mood disorder were hospitalized, and 24% of that group were re-hospitalized within a 3-month period. Comorbid substance abuse accounted for 36% of the initial hospitalizations and 50% of readmissions. These results suggest that comorbid HIV infection, mental illness, and substance abuse should be treated within a multidisciplinary partnership that includes mental health, infectious disease, and substance abuse professionals.

 suggest that a mental illness diagnosis in the absence of a substance abuse diagnosis is not highly associated with increased risk of HIV/AIDS. Substance abuse and symptoms of mental illness are relapsing and remitting. Therefore, relying on the presence or absence of one or another diagnosis at a given point fails to take a lifespan developmental view of mental illness and substance abuse.

Medication monitoring and drug-drug interactions

When prescribing psychotropic medication in the context of ART, it is important to monitor for untoward adverse effects, as well as to consider possible drug-drug interactions. For example, atypical antipsychotics increase the risk of metabolic syndrome, including weight gain, hyperglycemia, and hyperlipidemia. Similar symptoms associated with the metabolic syndrome are also associated with treatment with antiretroviral medications. Monitoring of weight, fasting blood glucose, and lipid profiles is integral to treatment for people who take any of these medications. Any drug-drug interactions between antiretroviral medications and psychotropic medications need to be identified. For example, specific benzodiazepines may be contraindicated when taken with protease inhibitors, and care must be taken when prescribing methadone in the presence of specific non-nucleoside reverse-transcriptase inhibitors. A careful history about the use of over-the-counter medications and herbal remedies is also recommended. In particular, St John’s wort may be contraindicated when used in conjunction with ART.

Tailored treatment and nurse health navigators

Preventing AIDS Through Health for HIV Positive (PATH+) persons was a regimen management intervention study for persons who also had a serious mental illness.

 An adaptive treatment design implemented through an intervention cascade was used to gear the intensity (and expense) of the intervention to adherence. A nurse health navigator (NHN) provided in-home consultations and coordinated medical and mental health services for 1 year. The protocol included a meeting with the patient at least once a week. Participants in the intervention group received psycho-education along with pillboxes and beeping watches. In addition, the NHN coordinated physician and other appointments for the patient and would accompany the patient if there was a problem with a medication, communication, or other issues that needed attention.

Adherence to HIV and psychiatric medications was calculated weekly. If adherence fell below 80%, the intervention cascade was implemented until adherence was maintained equal to or above 80% for 3 weeks. The intervention cascade represented a gradual increase in intensity and included activation of social networks, the use of reminder beepers with alphanumeric displays, and prepaid cellular phones to encourage participants to follow their regimen. If all else failed, the final step in the intervention cascade was directly observed therapy.

A total of 238 community-dwelling, HIV-positive patients with a serious mental illness were enrolled in the study. The main outcome measures were viral load and CD4 count. Assessments were conducted at baseline and at 3, 6, 12, and 24 months. Participants were followed for 12 months after the intervention ended in order to examine any recidivism. The results of the PATH+ study showed that with appropriate support, persons with a mental illness and HIV infection can successfully adhere to treatment and achieve improvements in health-related quality of life and biomarker health status indicators.

This article provides a brief overview of the interface between HIV infection and mental illness. The interested reader can peruse the cited references and a growing literature as well as the practice guidelines for additional information.

Other complexities involving HIV care and mental health include HIV-associated neurocognitive disorders that are increasingly recognized in clinical practice, but which are beyond the scope of this article. Treatment of HIV infection has come a long way since the epidemic first emerged, and thankfully the infection is rapidly becoming a manageable chronic illness. As with other chronic illnesses, HIV infection has specific psychiatric sequelae that are coming into sharper focus.

We still have a long way to go in terms of treatment options, updated guidelines, and tailored health services. Screening for depression and anxiety should occur at each infectious disease visit, and consultation and referral to specialty mental health providers should be seamless. The public health response to HIV infection and AIDS may be the finest example of the triumph of science and medicine over disease. In less than 4 decades we have managed to shift HIV infection from a disease of unknown origin that resulted in rapid decline and death, to a manageable chronic illness for which inoculation and cure are being sought.

There are successes to draw on, and perhaps nowhere have the positive impact and cost-effectiveness of prevention been so thoroughly demonstrated and accepted as in science-based HIV programs. The focus now needs to be on the co-occurrence of mental illness and HIV infection, along with the need to increase attention to the mental health risk and needs of HIV-positive persons.

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Articles

An overview of the interface between HIV/AIDS infection and mental illness.

Michael B. Blank, PhD

Articles

Mental Health and HIV/AIDS