The Effect of Divalproex Sodium on Viral Load: A Retrospective Review of HIV-Positive Patients With Manic Syndromes

Julie D Maggi, MD1, Mark H Halman, MD, FRCPC2

Objective: In vitro studies report that valproic acid causes an increase in HIV-1 replication. This retrospective study examines a sample of patients with HIV disease and behavioural disturbances, for which the treatment of choice is divalproex sodium (DVP), to determine whetherDVP causes an increase in HIV-1 replication.
Method: A chart and database review identified 15 patients with HIV disease presenting with either 1) mania or hypomania or 2) dementia with mania or with hypomania or behavioural disturbances. HIV-1 viral load was compared before and after mood stabilizer initiation.
Results: Eleven patients started therapy with DVP, and 4 patients declined treatment with a mood stabilizer. Nine of the 11 patients taking DVP were also receiving antiretroviral therapy. HIV-1 viral load did not increase in 6 of the 9 patients who had measurements between 1 week and 3.5 months after DVP initiation. No follow-up was available for the other 3 patients. Of the 2 patients receiving DVP but not antiretroviral medication, 1 had an increase of 0.17 log in HIV-1 viral load at 4 months. No follow-up record was available for the second patient. The 4 patients not taking DVP were all on antiretroviral therapy; viral loads in 2 of  them remained nondetectable over 3 to 4 months, and 1 had an increase of 0.32 log in HIV-1 viral load at 3 months. No follow-up record was available for the fourth patient.
Conclusions: These preliminary data suggest that, in the presence of effective antiretroviral therapy, HIV-1 viral load appears not to be adversely affected by the administration of DVP. The results for the patients receiving DVP in the absence of antiretroviral medication remain indeterminate. Further prospective study is required.

(Can J Psychiatry 2001;46:322-327)

Key Words: mania, HIV, AIDS, valproic acid, divalproex, HIV-1 viral load

Divalproex sodium (DVP) and its metabolite valproic acid (VPA) are anticonvulsant drugs indicated in the treatment of bipolar mood disorder (1,2) and may have a particular advantage over the traditional agents of lithium and antipsychotics in organic manic syndromes, including HIV-associated mania (3). Prevalence rates for manic syndromes in patients with HIV disease have been reported to be between 1.4% and 4% in ambulatory HIV–AIDS specialty clinics (3–5). These rates are comparable with the rate of manic syndromes in the general population, which is 1% (95%CI, 0.4% to 1.6%) (6).

Manuscript received May 2000, revised, and accepted September 2000.
This paper was presented as a Poster Presentation at the American Psychiatric Association Meeting, Washington, DC, 1999.
1Resident, Department of Psychiatry, University of Toronto, and St Michael’s Hospital Mental Health Service, Toronto, Ontario.
2Assistant Professor, Department of Psychiatry, University of Toronto; Director, HIV Psychiatry Program, St Michael’s Hospital Mental Health Service, St Michael’s Hospital, Toronto, Ontario.
Address for correspondence: Dr MH Halman, HIV Psychiatry Program, St Michael’s Hospital, Wellesley Site, 160 Wellesley Street East, Suite 334, Jones Building, Toronto, ON  M4Y 1J3
e-mail: mark.halman@utoronto.ca

Manic syndromes in patients with HIV disease may be caused by a primary bipolar mood disorder, or they may be secondary to medications used to treat HIV infection or its complications, or they may be secondary to a general medical condition, such as HIV brain infection or HIV-related central nervous system opportunistic conditions. Secondary mania is considered to be a late-stage consequence of HIV disease. It is accompanied by significant immunosuppression (3,4) and abnormal magnetic resonance (MR) imaging (3,4), and it may occur in patients with no personal or family history of mood disorders (5).

The optimal treatment of manic syndromes in patients with HIV disease remains unclear. One retrospective case series (3) and 1 case report (7) support the use of anticonvulsants over the traditional agents of lithium in combination with neuroleptics. In many HIV psychiatry clinics, VPA has emerged as the treatment of choice, not only for acute manic syndromes and bipolar disorder in HIV-infected patients, but also in managing the behavioural disturbances that may complicate HIV-associated dementia (3,7,8).

Recently, in vitro studies in both acutely and chronically infected cell lines have demonstrated that VPA activates HIV-1 replication at concentrations frequently reached in the plasma of VPA-treated patients (9–11).

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