HIV Psychiatry

Longitudinal Changes in Cognition and Brain Imaging in Persons With Human Immunodeficiency Virus
James Kennedy, Sarah A Cooley, June Roman Fox, Kalen J Petersen, Elizabeth Westerhaus, Pat Reid, Linet Lopez, Beau M Ances

Abstract:

Background. As persons with human immunodeficiency virus (PWH) live longer, interactions between human immunodeficiency virus (HIV), aging, and structural brain integrity become increasingly vital for understanding cognitive disorders. This study analyzed the effects of aging, HIV serostatus, and viral load on cognition and brain volumes in a large cohort of persons without HIV (PWOH), PWH with undetectable virus (PWHU) (HIV RNA ≤50 copies/mL), and PWH with detectable virus (PHWD) (HIV RNA >50 copies/mL). Cross-sectional and longitudinal data were included.

Methods. Cognitive composites (NPZ4) and brain volumes were obtained from 259 PWOH, 264 PWHU, and 84 PWHD with a total of 841 sessions. A series of generalized additive mixed models explored group differences in the relationship between age and cognition, age and regional brain volumes, and interactions between age and brain volumes on cognition.

Results. PWOH and PWHU exhibited similar change in cognitive performance with age, while PWHD exhibited a steeper decline compared to both. While both PWH groups had significantly smaller regional brain volumes compared to PWOH, the slopes of volume loss with age were similar across all groups except in the lentiform regions. Smaller brain volumes and increased age interacted for greater cognitive decline in PWHD.

Conclusions. PWH who achieve viral suppression do not exhibit accelerated decline in cognition or brain volumes compared to PWOH, while PWHD may be at an increased risk for accelerated cognitive decline. These findings highlight the clinical importance of managing viral load in aging PWH and suggest that once viral suppression is achieved, changes to brain integrity are not accelerated compared to PWOH.

Annotation

Findings: This large, single-site study, using a cross-sectional and longitudinal design, and spanning 16 years, compared the effects of aging and HIV on cognitive functioning and brain volumes among 3 cohorts: 1) persons without HIV (PWOH), 2) persons with undetectable virus (PWHU), and 3) persons with detectable virus (PWHD). Key findings were as follows: There was no difference in cognitive decline over time between PWOH and PWHU, while PWHD experienced a steeper decline in cognitive functioning, compared to the 2 other groups. Both groups with HIV demonstrated smaller regional brain volumes across most regions, compared to PWOH. However, the difference in brain volume between PWHU and PWHD reached statistical significance in only select regions: superior temporal cortex, lateral orbitofrontal cortex, putamen and precuneus. The rate of decline in brain volume was similar across all 3 groups in most regions with the exception of the putamen and globus pallidus. PWHD demonstrated faster decline in volume in the pallidum, compared to PWOH. In the putamen, rate of volume loss was greater in both HIV groups, compared to PWOH.

Strengths and limitations: This study had several notable strengths including its large sample size and inclusion of persons without HIV. Whereas previous research failed to separate PWH by virologic control, this study used a well-defined threshold of 50 viral copies/ml to distinguish between PWH with detectable vs undetectable viral loads. The use of structural MRI provided objective, quantitative regional brain volume measures. The study also included supplemental covariates such as depressive symptoms, substance use, and Area Deprivation Index, that enabled assessment of behavioral comorbidities and social determinants. Several limitations temper interpretation of results. A small minority of participants had greater than 2 study visits. PWHU were more likely to have multiple study visits than PWOH or PWHD, suggesting the possibility of selection bias. The cognitive battery utilized was relatively narrow which may have reduced sensitivity to domain-specific or subtle impairments. The PWHD group was significantly smaller compared to the other 2 groups which could have limited estimates for the unsuppressed group. The cohort comprised predominantly African American, male participants, thus limiting generalizability of findings to females and other ethnic groups. Subjects with fewer than 8 years of education, neurological disorders, or substance use disorders other than alcohol, tobacco and cannabis were excluded thus limiting participation to a relatively healthy group that were less likely to be at risk for cognitive decline. Cardiovascular disease, diabetes, and medication adherence were not fully accounted for.           

Relevance: It is estimated that over 50% of all people living with HIV in US are 50 years or older, a proportion that is expected to expand in coming years. Previous research on the effect of aging in persons with HIV on cognitive functioning and brain structure have yielded mixed results. This study’s strengths, described above, were an attempt to address problems that likely contributed to inconsistent past findings. Psychiatry can play an important role in monitoring cognition and early detection and intervention of impairments. Psychoeducation should include an emphasis on antiretroviral medication adherence and viral suppression. Similar to existing research, 2 of the most common and often co-occurring psychiatric disorders, depression and substance use, were strongly associated with cognitive decline and regional brain volume loss, suggesting these disorders as potential targets for intervention, especially in virologically suppressed participants. Social determinants of health, which also emerged as important risk factors for poor brain health, often accompany major psychiatric and substance related disorders. Study findings may also be of interest to Consultation-Liaison psychiatrists specifically, who are often asked to assess medical decision-making capacity, and should therefore be aware of the critical role of virologic suppression in maintaining brain health and in some cases reversal of HIV-related brain injury.

New-Onset Mania in the Setting of Progressive HIV Infection: A Case Report
Benjamin Walsh, Benjamin Kalivas

Abstract:

HIV infection has been known to cause or exacerbate psychiatric symptoms. In individuals with HIV, mania may present as part of a bipolar disorder or as a distinct condition referred to as Mania Associated with Advanced HIV Disease (previously known as AIDS mania). We present a case of a 57-year-old patient with new onset symptoms of bipolar disorder in the setting of HIV infection. The patient was admitted for treatment of mania and found to have an HIV infection, but with a CD4 + count that was still above the threshold of AIDS. Eventually, the patient's mood stabilized on a regimen of valproic acid 1500 mg twice daily and olanzapine 10 mg once daily. He developed infectious symptoms and was found to have cryptococcal pneumonia. He was started on fluconazole, but then subsequently left the hospital against medical advice.

Annotation

Bipolar disorder occurs with greater frequency in people with HIV than in the general population. It has been posited, though not firmly established, that symptoms of bipolar such as impulsivity, impaired judgment, and hypersexuality contribute to increased risk for HIV acquisition. However, it is generally accepted that HIV may cause secondary bipolar symptoms, referred to as Mania Associated with Advanced HIV Disease, MAAH, formerly called AIDS mania. MAAH has its onset late in the course of HIV infection and is characterized by no previous or family history of bipolar disorder, mood symptoms comprising mainly irritability, and significant cognitive impairment. This case report was unusual in its presentation before there was progressive loss of immune function and associated cognitive decline. Although the patient subsequently may have developed cryptococcal pneumonia, he did not test positive for cryptococcal meningitis, thus did not meet criteria for an AIDS diagnosis. Also, his cd4 cell count at time of HIV diagnosis was 275/ml with a viral load of 240 k copies/ml. Reports from earlier in the epidemic suggested that people with HIV were more vulnerable to developing mood symptoms when their immune systems were undergoing rapid decline, but prior to developing an AIDS-defining condition. This case report is consistent with that hypothesis. It also aligns with current research on chronic neuroinflammation underlying mood disorders, including both bipolar disorder and unipolar depression, in people without HIV. This case report is highly relevant for behavioral health professionals for several reasons. It highlights the need to evaluate patients for secondary causes of psychiatric symptoms, particularly when atypical features are present. It also argues for the routine inclusion of HIV screening, regardless of age, in patients presenting with new onset psychiatric symptoms. This patient illustrated one of the most vexing challenges facing psychiatrists working with patients with HIV: when psychiatric symptoms, such as lack of insight, impaired judgement and comprehension, and grandiosity lead to HIV medication nonadherence. In this case, the patient declined treatment with antiretroviral therapy, which likely limited his response to psychiatric medications and placed him at risk for progression of his HIV disease and transmission to others.