HIV Psychiatry

Article information
Title: HIV Diagnosis and Preexposure Prophylaxis (PrEP) Prescription Among Commercially Insured Persons with Bipolar Disorder
PubMed ID: 41396185
First Author Last Name: Bunting

Abstract:
Background:
Bipolar disorder (BD) is a severe and chronic mental illness characterized by periods of mania/ hypomania and depression. Both disease phases are associated with increased risk of acquiring HIV. Despite this, use of highly effective preexposure prophylaxis (PrEP) for HIV prevention among people with BD is poorly understood.

Methods:
We performed a retrospective cohort study using the Merative MarketScan Claims Database from 2010-2022 to identify people with BD. Additional clinical variables including outpatient encounters for sexually transmitted infections (STIs), use of long-acting injectable agents, psychiatric hospitalizations, and outpatient encounters with primary care providers (PCPs) and psychiatrists were included.

Results:
There were 333,867 people with BD (61.9% female) in the cohort. A total of 435 new HIV diagnoses were identified, with diagnoses more common among males (adjusted odds ratio [aOR] [95% CI]=5.30 [4.22-6.65], P<.001) and those with comorbid stimulant use disorder (aOR [95% CI]=2.40 [1.71-3.39], P<.001). A total of 1,337 people with BD were prescribed PrEP, and 909 were prescribed at least 3 months of PrEP. Among people with ≥4 encounters for STIs, 3.53% (n=246) were prescribed PrEP of any duration, and 2.73% (n=190) were prescribed PrEP for at least 3 months. People with BD who had outpatient encounters only with psychiatrists had greater odds of HIV diagnosis compared to those who had follow-up encounters with PCPs only (aOR [95% CI]=1.58 [1.11-2.27], P=.01) and lower odds of receiving PrEP prescription (aOR [95% CI]=0.74 [0.56-0.98], P=.03).

Conclusions:
PrEP use among commercially insured people with BD was critically low, with <1% prescribed PrEP. Even among those with multiple encounters for STIs, <4% were prescribed PrEP, despite this being an indication for prescription. Engagement of people with BD in the PrEP care continuum is essential for ending the HIV pandemic, and integration of PrEP prescription with psychiatric care may represent an efficient method for increasing PrEP use.

Annotation
Findings:
This retrospective cohort study used a large commercial, health insurance plan claims database from 2010-2022, to explore incidence and clinical correlates of HIV, as well as rates and clinical correlates of HIV preexposure prophylaxis (PrEP) use, among enrollees with bipolar disorder. The rate of new HIV diagnoses in people with bipolar disorder was over 10 times the rate found in the general population. Similarly, rates of PrEP use among people with bipolar disorder were critically low compared to the national rate of eligible people prescribed PrEP. This discrepancy was found even among those with multiple encounters for sexually-transmitted infections, an established indication for PrEP prescription. People with bipolar disorder who had outpatient encounters with only psychiatrists were more likely to be diagnosed with HIV, and less likely to be prescribed PrEP when compared to those with only outpatient primary care encounters.

Strengths and limitations:
It is well-known that people with bipolar disorder are at heightened risk of acquiring HIV, and that bipolar disorder is commonly associated with comorbid substance use disorders, social determinants of health, and other risk factors for HIV. Yet, this is the first study of its kind to explore PrEP use among this subpopulation of vulnerable individuals. Another major strength was the use of a very large database of approximately 151 million unique enrollees. The use of a commercial insurance database may also limit generalizability of findings beyond people with bipolar disorder who are employed, and may not apply to those with more severe disease. The use of ICD codes rather than structured interviews to identify subjects limits the accuracy of diagnoses. The use of claims data also misses PrEP prescriptions obtained by self-pay or other means. Additionally, the data do not permit assessment of HIV risk and PrEP eligibility at an individual level and thus do not offer deeper insight into the discrepancy between PrEP need and uptake. The lack of information about enrollee race/ethnicity prevents analysis of racial disparities which are a significant feature of HIV incidence and risk. Also, the use of high-risk sexual behavior codes may have been used inconsistently due to stigma.

Relevance:
This study offers foundational data supporting the need for increased attention to sexual health, early identification of HIV and STI risk behaviors, and access to biomedical HIV and STI prevention strategies for patients, especially those with severe mental illness. Comparing people with bipolar disorder who had only encounters with psychiatrists, versus those with only primary care encounters, the former were more likely to be diagnosed with incident HIV and less likely to be prescribed PrEP. This finding suggests a need for better and more specific methods of assessing PrEP eligibility and HIV risk among psychiatric patients. This gap in mental health clinicians’ practice is amplified since people with bipolar disorder, especially young adults, may be much more likely to have consistent and more frequent contact with a psychiatrist, as opposed to their primary care physician. PrEP is now available as a once every other month, long-acting injection of cabotegravir, or twice yearly subcutaneous, lenacapavir, long-acting injection, (LAI). LAI and oral PrEP prescriptions require laboratory testing and medication refills at least 4 times annually. The cadence of administration and monitoring of these PrEP formulations coincide with blood level and metabolic parameter management recommended for mood stabilizers and atypical antipsychotic drugs. Thus, seamless integration of psychiatric care and PrEP could be efficiently delivered. Over 50% of psychiatrists in a national survey were interested in prescribing PrEP, while the large majority felt insufficiently trained. Expansion of education and training of psychiatrists and mental health professionals about PrEP would advance the US national goal of ending the HIV epidemic and fill a significant gap in the care of patients with bipolar disorder and other forms of severe mental illness.

Article information
Title: A Placebo-Controlled Randomized Trial of the Effects of Escitalopram on Depressive Symptoms and Immune Function in People With HIV
PubMed ID: 41438415
First Author Last Name: Evans

Abstract:
Background:
This study was a randomized controlled trial investigating the effects of a selective serotonin reuptake inhibitor (SSRI) and improvement in depressive symptoms on innate immunity and inflammation in people with HIV (PWH).

Methods:
The mean 17-item Hamilton Depression Rating Scale (HAMD-17) score at baseline was 19.1 for the sample (N = 108). Eligible participants were randomized to 10 weeks of double-blind therapy with either SSRI (escitalopram) or placebo. All participants concurrently received computer-assisted cognitive behavioral therapy (CCBT). Peripheral blood was obtained from each participant at baseline and at weeks 2, 4, and 10, and intracellular interferon gamma (IFN-γ) in natural killer (NK) cells, lytic units per 107 NK cells (LUNKs), interleukin 6 (IL-6), and C-reactive protein (CRP) were measured.

Results:
Participants showed substantial reduction in depressive symptoms during study with final HAMD-17 score of 8.00 (average decrease of 11.0 units). However, there was no statistically significant effect of treatment, whether viewed as a group × time interaction (F 1,166 = 0.00, p = .976) or as a main effect for group (F 1,667 = 0.50, p = .479). There were no statistically significant differences between the groups on the immune parameters over time. There was little evidence that the magnitude of symptom improvement was associated with changes in immune measures.

Conclusions:
Our study did not demonstrate superiority of treatment with SSRI+CCBT versus placebo+CCBT. Patients in both arms showed improvement of depression symptoms, which did not correlate with changes in immune markers. We found no evidence of decreased inflammation (IL-6, CRP) or immune restoration (LUNKs or intracellular IFN-γ) following treatment with CCBT with or without active escitalopram. While antidepressant treatment is indicated for PWH with depression, we observed no evidence of direct immunologic benefits.

Annotation
Findings:
This randomized, double-blind, placebo-controlled trial explored the effect of citalopram plus computerized cognitive behavioral therapy (CCBT) on depressive symptoms and biomarkers of innate immunity and inflammation in people with HIV. Citalopram plus CCBT performed no better than placebo plus CCBT at reducing depressive symptoms over the 10-week study period. Both groups experienced significant improvement in HAM-D scores. Additionally, there was no correlation, in either arm, between depressive symptom reduction and improvement in biomarkers for either innate immunity or inflammation. The study failed to confirm the hypothesis that an SSRI, escitalopram, would have a specific, beneficial effect on immune functioning and systemic inflammation, that was superior to placebo, in depressed participants with HIV.

Strengths and limitations:
This study’s strengths included its randomized, double-blind, placebo-controlled design and relatively large sample size. This was the first study with this rigorous design to investigate the use of an SSRI to treat depression in HIV with a focus on immune regulation and systemic inflammation. The study also had several important limitations. A significant proportion of participants had mild depressive symptoms at baseline. This is important since efficacy of antidepressant drugs in prior RCTs has been shown to be dependent on severity of depressive symptoms at study entry. Additionally, the majority of participants in this study received lower than ideal doses of citalopram. Response may have been further attenuated by the combination of psychotherapy in both study arms. It is also noteworthy that the study included only participants with sustained viral suppression. Thus, the study may have yielded results more informative of the study hypotheses if it had included participants with more severe depression and higher viral loads. Higher levels of associated inflammatory markers may have been more likely to show changes following treatment. The study did not also enroll matched control groups, whether healthy or HIV-infected, and thus limits interpretability of findings. This study excluded participants with a history of treatment-resistant depression. This is significant since previous research has demonstrated elevated levels of proinflammatory markers in patients with poor response to treatment with antidepressant medication.

Relevance:
Depressive disorders are highly prevalent and are among the most common reasons for psychiatric consultation in people with HIV. Depression is also a risk factor for the development of HIV-associated neurocognitive disorder (HAND) and commonly co-occurs with other psychiatric disorders that are overrepresented in PWH such as anxiety and substance use disorders. The importance of understanding immunologic mechanisms underlying emergence of depressive symptoms and untangling their relationship to HIV-associated immune dysregulation, cannot be overstated. Drawing on a large body of research involving depression, systemic inflammation and immunology, this is the largest study of its kind to focus on innate immunity and the effect of SSRIs, agents with demonstrated direct action on peripheral immune cells. Although findings did not support the study’s hypotheses, they suggested modifications and directions for future research at the interface of neuroimmunology and HIV.