TREATMENT OF HIV- ASSOCIATED NEUROCOGNITIVE DISORDERS (HAND)

In the chapter, ‘Treatment of Psychiatric Disorders in HIV’, Ferrara et al. present a comprehensive review of the literature that has accrued over the past 25 years of work in HIV psychiatry.

With a strong focus on the use of antiretroviral medications for the treatment of HIV-associated neurocognitive disorders (HAND), the authors point out the significant impact that sustained virological control has had on HIV dementia, the most severe form of HAND. The impact has been considerably less on the prevalence of milder forms of HAND: mild neurocognitive disorder (MND) and asymptomatic neurocognitive impairment (ANI), suggesting that whilst highly active antiretroviral therapy (HAART) and full viral suppression are necessary for the treatment of HAND, they are not the entire story. Investigations into other strategies, including immune modulators and neuroprotective agents have yielded disappointing effectiveness results and such agents have not generally made their way into clinical use. Emerging investigations into behavioural interventions and neurorehabilitation strategies that focus on functional outcomes may point to important strategies that will complement medication management and enhance quality of life for patients with HAND.

Many questions remain under investigation in the use of HAART in the treatment and prevention of HAND. General treatment guidelines for the systemic management of HIV care are not yet adapted for brain-related issues but the observation that severity of HAND is correlated with nadir CD4 count may support the notion that earlier intervention, particularly in patients at increased risk for neurocognitive impairment, may be a useful strategy [1]. The preferential use of agents that are more effective at penetrating the central nervous system has found some advantage in suppressing cerebrospinal fluid CSF viral load and in some instances reducing the rates of HAND [2], though there is not yet evidence to support their preferential use in the prevention of HAND. The possibility that HAART agents may reach neurotoxic levels in the central nervous system contributing to neurocognitive symptoms needs further investigation as our understanding of neurocognitive syndromes in HIV further develops. With the development of consensus documents, new evidence-based guidelines advocating increased monitoring and screening of neurocognitive performance and relevant clinical trials, it is anticipated that answers to these important clinical questions will become further clarified [3].

PHARMACOTHERAPY FOR DEPRESSION AND PSYCHOTIC DISORDERS

The evidence to guide clinicians in prescribing psychotropic medications to patients living with HIV infection (PLWH) is considerably more limited. This is surprising considering the high rates of psychiatric symptoms that have been described in HIV illness. The adverse impact of depressive symptoms on HAART adherence has been well documented and data suggests that mental illness and substance use disorders must be effectively treated in order to improve HAART adherence in PLWH living with concurrent disorders [4]. A recent review of pharmacotherapy in PLWH found only 11 randomized controlled antidepressant trials and only one antipsychotic trial [5]. These trials support the use of selective serotonin reuptake inhibitors (SSRI) medications as well as tricyclic antidepressants TCAs in the treatment of depression in PLWH. The data supporting the use of antipsychotics and mood stabilizers is even more limited. The only randomized controlled trial (RCT) conducted with antipsychotic medications examined the use of chlorpromazine versus haloperidol in the treatment of delirium [5]. There are no RCTs looking at these classes of drugs in PLWH with primary psychiatric disorders such as schizophrenia or bipolar disorder. As a field, we need to generate a larger body of evidence to guide psychotropic prescribing in the setting of complex medication regimens and become better able to provide guidance to PLWH with a range of mental health disorders.

In the absence of evidence, we are left to rely on open-label trials, case studies and reports, inferences from general psychiatry and clinical judgement. There is little evidence to support the use of general guidelines that many of us clinicians have adopted over the years. ‘Start low and go slow’ makes good practical sense but has not been well tested as a strategy. Nor has the strategy of selecting psychotropic agents based on a desire to exploit potential side effects, such as weight gain, been shown to yield more clinically effective results, though again it is clinically reasonable to do. The desire to avoid complex regimens makes good sense, as it will potentially limit side effects, overlapping toxicities and drug interactions [6]. However, it may not be such a good strategy if it leads to mental illness in HIV-positive patients being consistently undertreated.

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