Manic episodes are more common in people with HIV infection than in the general population.[27] An episode of mania is often associated with poor impulse control, impaired judgment and greater risk-taking behaviours, increasing the chance of contracting or spreading HIV infection.

A manic episode may be primary (related to a bipolar disorder) or secondary to a range of other causes.[28] Possible secondary causes are substance-induced mania related to either illicit or prescription medications including antiretroviral drugs, mania due to a medical condition such as central nervous system opportunistic infection, a manifestation of a hyperactive delirium, or related to primary HIV infection.[29]

Important clinical features to consider on history taking include a past or family history of a mood disorder, current HIV clinical parameters and stage, current medications and recent changes, substance abuse history and a cognitive assessment. Specific enquiry regarding increased libido or sexual activity should also be made as previously insightful patients may lose their usual judgment, e.g. occasionally develop delusions and believe that their HIV infection is cured. A comprehensive medical examination is required and investigations, such as neuroimaging and CSF analysis, should be undertaken to determine if there is CNS involvement by HIV infection.

Manic episodes related to HIV infection tend to be a late manifestation of HIV disease associated with a low CD4+ T cell count, high HIV viral load, evidence of structural brain damage demonstrable on magnetic resonance image (MRI) or computed tomography (CT) scans or neuropsychological deficits.[30] These episodes classically have been associated with cognitive impairment and a poor clinical prognosis, as they have been linked to the development of an HIV-associated dementia.[31] Clinically, patients may present with more irritability, talkativeness and cognitive slowing and impairment than those with primary bipolar illness. Treatment must be provided in a safe and secure environment. This recommendation may mean consideration of hospitalisation and involuntary treatment.

Evidence suggests that the most effective treatment for HIV-associated mania is ART that penetrates the CNS.[32] Symptoms may also be controlled with psychotropic medications, including mood stabilisers, antipsychotic and anxiolytic drugs. All mood stabilisers have the potential for side effects and drug interactions. Lithium is reported to be effective but has higher rates of neurotoxicity in this population. Sodium valproate is frequently used but care must be taken to monitor for liver toxicity and the theoretical risk of elevation of HIV viral load. Mood stabilisers are often combined with antipsychotic drugs to treat acute episodes. Current practice suggests that olanzapine, risperidone and quetiapine can be effective in this population, though there is an increased rate of extrapyramidal side effects. Benzodiazepines are also used for short-term sedation.[33]