People with HIV infection suffer high rates of major depression. A meta-analysis found rates of major depression in HIV-positive people to be twice that of matched HIV-negative controls.[15] Rates may increase with HIV disease progression and symptomatic illness.[16] Certain risk factors are associated with an increased risk of depression: a personal or family history of mood disorders, substance use, anxiety disorders, suicidal episodes, being female, low social support, and current medical illness.[17] Suicidal thoughts and acts are a common reason for psychiatric referral and can occur at times of crisis, such as at the time of HIV diagnosis and in the late stages of illness. Depression may adversely affect the outcome of treating HIV infection. There is evidence to support an association between depression and self-neglect, with implications for treatment adherence.[18]

It can be difficult to identify depression in patients with severe medical illness. Depressive symptoms may represent a normal reaction to physical illness, a manifestation of the underlying physical illness (e.g. symptoms of fatigue and anorexia) or a component of a depressive syndrome. As such, depression can be easily missed. Untreated depression in patients is associated with a worse prognosis.[19] Cognitive-affective symptoms (as opposed to somatic symptoms) may be more discriminating in identifying depression in this population. Examples of these symptoms would be: a sense of failure, a sense of being punished, indecisiveness, reduced social interest, suicidal ideation, frequent crying and dissatisfaction.[20] In patients with HIV infection it is always important to consider an organic basis to the depression, especially when there is no personal or family history of a mood disorder, there are no obvious precipitants, when the presentation is atypical, when cognitive symptoms appear severe, if the patient is severely immunocompromised or when the patient had failed to respond to treatment. Assessment needs to include a thorough physical examination and medical workup to exclude organic pathology (Table 1).

Table 1. Assessment of patients with HIV infection attending with psychiatric symptoms

Psychosocial history

Living environment, employment, finances, relationships.

Level of functioning

Activities of daily living; presenting symptoms and relationships to psychosocial factors.

HIV status

Duration of illness; current CD4+ T cell count and HIV viral load; CD4+ T cell count nadir (indicates likelihood of CNS involvement); HIV disease manifestations, particularly opportunistic infections; current antiretroviral therapy (ART) and recent changes and adherence to ART.

Medical and psychiatric history

Other active medical problems and medications; personal and family history of previous mental illness; comprehensive drug and alcohol use assessment.


Mental state assessment with focus on cognition and risk assessment. Physical examination, as indicated to identify and exclude organic illness.


CD4+ T cell count and HIV viral load, if not recently determined.

Appropriate CNS investigations if CD4+ T cell count < 200/μL and clinically indicated, e.g. CSF examination (HIV RNA level and cryptococcal antigen) and neuroimaging.

Renal and liver function tests, vitamin B12/folate, blood glucose, full blood count, serum CRP, thyroid function tests and consider pituitary function tests and serum testosterone level, urine drug screen.

Review past serology tests, particularly those for syphilis.

CNS = central nervous system; CSF = cerebrospinal fluid.

The appropriate treatment approach in the patient with HIV infection and depression depends on the type and severity of the depression (Table 2). Once organic illness is excluded or reversed, for mild depression, treatment with short-term psychotherapy alone is usually appropriate and there is evidence to suggest efficacy.[21] This treatment could be supportive, cognitive behavioural or interpersonal psychotherapy and needs to be provided by trained clinicians. For moderate-to-severe depression, antidepressant medications are recommended, often in combination with psychological therapies. The choice of antidepressant depends on the patient’s symptom profile and history of prior response. Though there is evidence for good effect with tricyclic antidepressants,[22] given their side-effect profile and risk in overdose, current first-line therapy would be a selective serotonin reuptake inhibitor (SSRI) antidepressant. It is better to choose an agent with fewer drug-drug interactions such as citalopram, escitalopram or sertraline. Second-line agents include mirtazapine, which aids insomnia and poor appetite, or venlafaxine. For more severe depression associated with melancholic or psychotic symptoms it is advisable to seek advice from a trained psychiatrist as treatment may require the use of augmentation with antipsychotic drugs or mood stabilisers, and, rarely, electroconvulsive therapy.

Table 2. Treatment of HIV patients with psychiatric symptoms

Engagement and therapeutic rapport

Identify and contain risks and consider need for involuntary treatment.

Obtain further history from family or partner, as indicated.

Notify child protection agencies, if indicated.

Consider need for referral to specialist care.

Exclusion of organic illness

Further physical examination and investigations, as indicated


Identify and treat underlying psychiatric illness e.g. antidepressants, mood stabilisers, antipsychotics, as indicated.

Consider use of short-term anxiolytic or hypnotic drug to contain symptoms and aid engagement.

Consider need for drug or alcohol withdrawal regimen, if indicated.

Monitor for medication side effects and review adherence.


Educate the patient about identified illness and recovery plan.

Determine if specialist psychological approaches are required: short-term cognitive behavioural, or interpersonal therapy and longer-term psychodynamic approaches, as indicated.

Instigate partner and family interventions, as indicated.

Consider motivational interviewing as an approach to drug and alcohol dependence.

Consider if a neuropsychology assessment is required.


Consider role of multidisciplinary team, including the role of social workers in housing, financial support, employment, relationships (support groups) and home supports to reduce stressors.

Consider need for support from drug and alcohol services.