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Brief Reports   |    
Bipolar Medication Use and Adherence to Antiretroviral Therapy Among Patients With HIV-AIDS and Bipolar Disorder
James T. Walkup, Ph.D.; Ayse Akincigil, Ph.D.; Sujoy Chakravarty, Ph.D.; Mark Olfson, M.D., M.P.H.; Scott Bilder, M.S.; Shahla Amin, M.S.; Michele J. Siegel, Ph.D.; Stephen Crystal, Ph.D.
Psychiatric Services 2011; doi: 10.1176/appi.ps.62.3.313
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A preliminary version of this report was presented at the International Association of Physicians in AIDS Care-NIMH 5th International Conference on HIV Treatment Adherence, May 23–25, 2010, Miami, Florida.

Copyright © 2011 by the American Psychiatric Association.

Objective:  The study examined relationships between adherence to bipolar medication and to antiretroviral therapy, measured by medication fills, among patients with diagnoses of bipolar disorder and HIV infection.

Methods:  A retrospective study was conducted of Medicaid claims data (2001–2004) from eight states, focusing on antiretroviral adherence. The unit of analysis was person-month (N=53,971). The average observation period for the 1,687 patients was 32 months. Analyses controlled for several patient characteristics.

Results:  Patients possessed antiretroviral drugs in 72% of the person-months. When a bipolar medication prescription was filled in the prior month, the rate of antiretroviral possession in the subsequent month was 78%, compared with 65% when bipolar medication was not filled in the prior month (p<.001). Odds of antiretroviral possession were 66% higher in months when patients had a prior-month supply of bipolar medication.

Conclusions:  Bipolar medication adherence may improve antiretroviral adherence among patients with bipolar disorder and HIV infection. (Psychiatric Services 62:313–316, 2011)

Abstract Teaser
Figures in this Article

Rates of HIV infection are elevated among people with severe mental illness compared with the general population (1). This increase likely reflects a range of factors, including risky behaviors secondary to psychiatric symptoms (2) and co-occurring substance use disorders (3).

Individuals with bipolar disorder generally require long-term pharmacotherapy and attention to psychosocial stressors to promote stability. Manic symptoms, such as poor impulse control and impaired judgment, as well as a high rate of comorbid substance abuse may increase risk of HIV infection (4), which is elevated among persons with bipolar disorder (5).

Antiretroviral therapy is the principal treatment for HIV-AIDS, and because suboptimal adherence can result in resistant viral strains and disease progression, medication adherence is vital for public health and for individual outcomes (6). Severe psychiatric disorders and substance abuse both influence adherence to antiretroviral therapy (7). An observational study suggested that the impact may differ by disorder; the effects of schizophrenia on adherence to antiretroviral therapy may be less than those of major depression and bipolar disorder (8). Clinical characteristics of bipolar disorder that increase risk of HIV infection, including manic symptoms and co-occurring substance use disorders, may also put optimal adherence in jeopardy.

If mania and other psychiatric symptoms decrease adherence to antiretroviral therapy, then treating these symptoms may increase adherence. Yet support for this hypothesis is surprisingly limited; we are not aware of published studies that examine this issue among persons with bipolar disorder. Among patients with HIV-AIDS and depression, some evidence points to an association between antidepressant adherence and antiretroviral adherence (9,10), but difficulties establishing the nature of the association with observational data have been noted.

In this study we examined adherence to antiretroviral therapy among persons living with HIV-AIDS who had a diagnosis of bipolar disorder. We report associations with demographic and clinical characteristics. We hypothesized that bipolar medication adherence in the preceding month would be associated with adherence to antiretroviral therapy in the following month and that a comorbid diagnosis of a substance use disorder would be associated with lower rates of adherence to antiretroviral therapy.

This study utilized Medicaid Analytic Extract data sets from 2001 to 2004 from eight states, which contained data for 4,568,010 individuals who were enrolled in Medicaid for at least one month. The eight states were California, New York, New Jersey, Georgia, Ohio, Illinois, Texas, and Florida. Person- and claims-level information was used, including ICD-9-CM diagnosis codes, National Drug Codes, and pharmacy dispense dates for every medication for which a prescription was filled. ICD-9-CM codes used to identify bipolar disorder were 296.0, 296.1, and 296.4–296.8; for HIV they were 042–044; for substance use disorders they were 291, 292, and 303–305; and for schizophrenia the code was 295.

Using a person-month as the unit of analysis, we classified each person-month as covered or not covered by antiretroviral therapy and by medication for bipolar disorder. Medications for bipolar disorder included lithium, antipsychotics, and the anticonvulsants carbamazepine, oxcarbazepine, valproate, and lamotrigine. We excluded gabapentin and topiramate, which do not demonstrate efficacy in randomized clinical trials. Because most Medicaid prescriptions for antiretroviral therapy and bipolar medications were for 30 days, with only 2% of antiretroviral therapy and 3% of bipolar medication prescriptions exceeding 31 days, we classified each calendar month as covered if a prescription for the medication was filled in that month.

Participants were aged 18 to 65 years and during 2001–2004 had at least one inpatient or two outpatient claims for bipolar disorder, one inpatient or outpatient claim for HIV, plus at least one pharmacy claim for antiretroviral therapy and one for bipolar medications. We analyzed treatment episodes, defined as starting with the first month during which prescriptions for both bipolar and antiretroviral medications were filled. Only patients who remained enrolled in Medicaid for at least one year after this start date were included. Patients who also had a diagnosis of schizophrenia were excluded. Finally, we included only fee-for-service beneficiaries who were continuously enrolled in Medicaid and who did not receive long-term care or have nursing home days. Covariates included the state and the beneficiary's gender, age, race-ethnicity, and diagnosed substance use disorders.

Using multivariate logistic regression, we treated a refill for antiretroviral therapy in a given month as a dependent variable and treated a refill for bipolar medication in the prior month as a predictor variable. We chose this “lagged” strategy because same-month correlations between bipolar medication refills and antiretroviral refills would have included, for example, simultaneous refills occurring in a single pharmacy visit and would therefore have been less reflective of a causal direction running from bipolar treatment to antiretroviral adherence. Independent variables included patient characteristics, as well as the interaction of each covariate with the indicator of lagged bipolar medication possession, in order to delineate whether the effect of bipolar medication use varied by patient characteristics. Analyses took into account statistical dependence of repeated observations within individuals by using the cluster option within the logistic regression procedure in Stata, version 9.2. We utilized SAS, version 9.2, for data management. This research was approved by the Rutgers University Institutional Review Board.

We identified 10,971 beneficiaries with both bipolar disorder and HIV infection. The criteria regarding age, long-term and managed care, and one year of continuous enrollment after the start of the treatment episode reduced the sample to 2,631. Eliminating beneficiaries with schizophrenia reduced the sample to 1,687. The mean±SD observation period for the 1,687 persons was 32±4.6 months (N=53,971 person-months). Antiretroviral therapy medications were refilled in 72% of the months, and bipolar medications were refilled in 55%.

Confirming our primary hypothesis, we found that adherence to bipolar medication was associated with higher rates of adherence to antiretroviral therapy in the following month. As shown in Table 1, when bipolar medication was not filled in the prior month, the rate of antiretroviral fill in the subsequent month was 65%, compared with an antiretroviral fill rate of 78% when bipolar medication was filled in the previous month. The association remained significant after the analysis controlled for demographic characteristics and diagnoses of comorbid substance use disorders and their interactions. Adherence to antiretroviral therapy was higher for men than women. Fill rates for antiretroviral medications were highest for beneficiaries aged ≥50 and lowest for the youngest beneficiaries. As hypothesized, diagnosis of a comorbid substance use disorder was associated with a significantly lower antiretroviral adherence rate (adjusted odds ratio=.62).

We found a temporal association between receipt of bipolar medication and subsequent receipt of antiretroviral therapy in an analysis that controlled for several potentially confounding background demographic and clinical variables. Limitations should be noted. By requiring one year of observation, we may have missed less stable patients. Clinical status was observed by diagnoses, which lack valuable details (for example, a diagnosis of a substance use disorder does not necessarily indicate actual use during the observation period). It cannot be determined from prescription claims whether a patient ingests a medication. Experimental designs—particularly randomized controlled trials—are required to isolate a specific medication effect, although practical and ethical difficulties in this research area make randomized controlled trials challenging. Nevertheless, future investigations that include longitudinal collection of data on symptoms would allow researchers to assess the role of symptom control, mood stabilization, active substance use, and phase of disorder in supporting adherence to antiretroviral therapy for patients with bipolar illness and HIV-AIDS. The study was also limited to adult Medicaid beneficiaries in various phases of bipolar disorder who had already initiated bipolar medications and antiretroviral therapy. It is not clear whether similar results would have been obtained for other patient populations.

Our findings converge with those of previous research in suggesting that among persons with HIV and serious mental illness, adherence to a psychoactive medication regimen can improve adherence to antiretroviral therapy (8). Because of the central clinical importance of antiretroviral adherence, it seems appropriate that patients with bipolar disorder and HIV have individualized and ongoing assessments of their capacity to adhere to antiretroviral therapy. Adherence may fluctuate with clinical status. The findings underline the importance of psychopharmacological treatment in this population, both to benefit bipolar symptoms and to promote antiretroviral adherence.

This work was supported by grants R01-MH076206 and R01-MH058984 from the National Institute of Mental Health (NIMH), with additional support from the Agency for Healthcare Research and Quality (AHRQ) through cooperative agreement U18HS016097 for the Center for Research and Education on Mental Health Therapeutics at Rutgers, as part of AHRQ's Centers for Education and Research on Therapeutics Program. The content is solely the responsibility of the authors and does not necessarily reflect the official views of NIMH or AHRQ.

Dr. Olfson has received research funding from Eli Lilly and Company and Bristol-Myers Squibb. The other authors report no competing interests.

Angelino  AF;  Treisman  GJ:  Issues in co-morbid severe mental illnesses in HIV infected individuals.  International Review of Psychiatry 20:95–101, 2008
 
McKinnon  K;  Cournos  F;  Sugden  R  et al:  The relative contributions of psychiatric symptoms and AIDS knowledge to HIV risk behaviors among people with severe mental illness.  Journal of Clinical Psychiatry 57:506–513, 1996
 
Meade  CS;  Sikkema  KJ:  HIV risk behavior among adults with severe mental illness: a systematic review.  Clinical Psychology Review 25:433–457, 2005
 
Meade  CS;  Graff  FS;  Griffin  ML  et al:  HIV risk behavior among patients with co-occurring bipolar and substance use disorders: associations with mania and drug abuse.  Drug and Alcohol Dependence 92:296–300, 2008
 
Beyer  JL;  Taylor  L;  Gersing  KR  et al:  Prevalence of HIV infection in a general psychiatric outpatient population.  Psychosomatics 48:31–37, 2007
 
Kemppainen  JK;  Levine  R;  Buffum  M  et al:  Antiretroviral adherence in persons with HIV/AIDS and severe mental illness.  Journal of Nervous and Mental Disease 192:395–404, 2004
 
Himelhoch  S;  Brown  CH;  Walkup  J  et al:  HIV patients with psychiatric disorders are less likely to discontinue HAART.  AIDS 23:1735–1742, 2009
 
Walkup  JT;  Sambamoorthi  U;  Crystal  S:  Use of newer antiretroviral treatments among HIV-infected Medicaid beneficiaries with serious mental illness.  Journal of Clinical Psychiatry 65:1180–1189, 2004
 
Yun  LW;  Maravi  M;  Kobayashi  JS  et al:  Antidepressant treatment improves adherence to antiretroviral therapy among depressed HIV-infected patients.  Journal of Acquired and Immune Deficiency Syndrome 38:432–438, 2005
 
Walkup  J;  Wei  W;  Sambamoorthi  U  et al:  Antidepressant treatment and adherence to combination antiretroviral therapy among patients with AIDS and diagnosed depression.  Psychiatric Quarterly 79:43–53, 2008
 
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Table 1

Characteristics associated with filled antiretroviral prescriptions among adult Medicaid patients with diagnoses of bipolar disorder and HIV infection

Table 1 

Characteristics associated with filled antiretroviral prescriptions among adult Medicaid patients with diagnoses of bipolar disorder and HIV infection

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References

Angelino  AF;  Treisman  GJ:  Issues in co-morbid severe mental illnesses in HIV infected individuals.  International Review of Psychiatry 20:95–101, 2008
 
McKinnon  K;  Cournos  F;  Sugden  R  et al:  The relative contributions of psychiatric symptoms and AIDS knowledge to HIV risk behaviors among people with severe mental illness.  Journal of Clinical Psychiatry 57:506–513, 1996
 
Meade  CS;  Sikkema  KJ:  HIV risk behavior among adults with severe mental illness: a systematic review.  Clinical Psychology Review 25:433–457, 2005
 
Meade  CS;  Graff  FS;  Griffin  ML  et al:  HIV risk behavior among patients with co-occurring bipolar and substance use disorders: associations with mania and drug abuse.  Drug and Alcohol Dependence 92:296–300, 2008
 
Beyer  JL;  Taylor  L;  Gersing  KR  et al:  Prevalence of HIV infection in a general psychiatric outpatient population.  Psychosomatics 48:31–37, 2007
 
Kemppainen  JK;  Levine  R;  Buffum  M  et al:  Antiretroviral adherence in persons with HIV/AIDS and severe mental illness.  Journal of Nervous and Mental Disease 192:395–404, 2004
 
Himelhoch  S;  Brown  CH;  Walkup  J  et al:  HIV patients with psychiatric disorders are less likely to discontinue HAART.  AIDS 23:1735–1742, 2009
 
Walkup  JT;  Sambamoorthi  U;  Crystal  S:  Use of newer antiretroviral treatments among HIV-infected Medicaid beneficiaries with serious mental illness.  Journal of Clinical Psychiatry 65:1180–1189, 2004
 
Yun  LW;  Maravi  M;  Kobayashi  JS  et al:  Antidepressant treatment improves adherence to antiretroviral therapy among depressed HIV-infected patients.  Journal of Acquired and Immune Deficiency Syndrome 38:432–438, 2005
 
Walkup  J;  Wei  W;  Sambamoorthi  U  et al:  Antidepressant treatment and adherence to combination antiretroviral therapy among patients with AIDS and diagnosed depression.  Psychiatric Quarterly 79:43–53, 2008
 
References Container
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