What is the most appropriate initial diagnosis for a 47‑year‑old African‑American man with chronic human immunodeficiency virus infection, recent traumatic event, homelessness, persistent low mood, anhedonia, weight loss, and functional decline?

Major Depressive Disorder

The most appropriate initial diagnosis for this patient is Major Depressive Disorder (MDD), given the presence of persistent low mood, anhedonia, weight loss, and functional decline following a recent traumatic event in the context of chronic HIV infection.

Rationale for Depression Diagnosis

The clinical presentation meets screening criteria for depression based on guideline-recommended questions. According to HIVMA/IDSA guidelines, all patients should be screened with two key questions: "During the past 2 weeks have you often been bothered by feeling down, depressed, or hopeless?" and "During the past 2 weeks have you been bothered by little interest or pleasure in doing things?" 1. This patient's persistent low mood and anhedonia directly correspond to positive responses to both screening questions.

Depression is highly prevalent among HIV-infected patients, particularly in the context of recent major loss or grief, homelessness, and traumatic events—all of which are potentially modifiable risk factors that should be assessed 1. The combination of mood changes, weight loss, and functional decline strongly suggests MDD rather than HIV disease progression alone 1.

Confirming the Diagnosis

Use the Patient Health Questionnaire-9 (PHQ-9) immediately to confirm and quantify depression severity 1. A PHQ-9 score ≥10 has 88% sensitivity and 88% specificity for major depression and warrants psychiatric follow-up 1. This validated tool is particularly useful in clinical settings without immediate access to mental health professionals 1.

The diagnosis should be distinguished from:

• HIV-related symptoms alone: While weight loss and low-grade fever can occur with HIV disease progression 2, the prominent mood and anhedonia symptoms point toward MDD
• Adjustment disorder: The persistence and severity of symptoms, combined with functional impairment, suggest MDD rather than a milder adjustment reaction
• Post-traumatic stress disorder (PTSD): Given the recent traumatic event, PTSD should be screened for as a comorbid condition, as it is highly prevalent in HIV-infected individuals (5-74% prevalence) 3, 4 and often co-occurs with depression 5

Critical Assessment Points

Screen for PTSD concurrently, as the recent traumatic event is a significant risk factor 1. Depression and PTSD frequently coexist in HIV-infected patients, with PTSD prevalence rates substantially higher than the 7-10% seen in the general population 3. Both conditions independently predict poorer adherence to antiretroviral therapy 3, 4.

Evaluate substance use immediately 1, 6. Depression and substance abuse are tremendous barriers to consistent adherence to antiretroviral therapy 1. Active substance use and mental illness, especially depression, are the strongest predictors of inadequate adherence to HIV medications 6.

Assess suicidal ideation and safety 1. The combination of depression, recent trauma, homelessness, and social instability increases suicide risk. History of serious mental illness or suicidal ideation is a potentially modifiable risk factor that must be addressed 1.

Addressing Homelessness and Social Determinants

The patient's homelessness represents a critical barrier to treatment adherence and recovery. Early assessment by a qualified social worker or case manager is essential to identify social and economic factors affecting adherence 6. Strengths-based case management should be initiated, as this increases the likelihood of attending HIV clinic visits from 60% to 78% 6.

Common Pitfalls to Avoid

• Do not attribute all symptoms to HIV disease progression: With chronic HIV infection, psychiatric comorbidities are common and require independent evaluation 1
• Do not delay depression screening: Depression screening should occur at initial evaluation and at periodic intervals thereafter 1
• Do not overlook the impact on antiretroviral adherence: Untreated depression directly impairs medication adherence and HIV outcomes 1, 6
• Do not miss comorbid PTSD: The recent traumatic event necessitates PTSD screening, as this condition independently affects treatment adherence and health outcomes 3, 4, 5

Immediate Next Steps

After confirming MDD diagnosis with PHQ-9:

• Initiate or optimize depression treatment (pharmacotherapy and/or psychotherapy), as treatment of depression can improve medication adherence 1
• Ensure antiretroviral therapy is continued and assess adherence barriers 6
• Connect with case management services to address homelessness and social needs 6
• Screen for substance use disorders using validated tools 1, 6
• Assess for PTSD symptoms related to the recent traumatic event 1, 3