In a male patient with recurrent infections, weight loss, oral thrush, generalized lymphadenopathy, low‑grade fever, a history of unprotected sexual intercourse with multiple partners and intravenous drug use, which cell is the primary target destroyed by the infectious agent?

CD4 T Cells Are the Primary Target

The infectious agent in this patient—HIV—primarily destroys CD4 T cells (also known as T-helper lymphocytes), which is the hallmark mechanism of AIDS pathogenesis. 1

Clinical Presentation Confirms HIV Infection

This patient's constellation of findings is classic for HIV/AIDS:

• Risk factors: Unprotected sexual intercourse with multiple partners and IV drug use are the two primary transmission routes for HIV 2
• Recurrent infections: Result from progressive CD4 T cell depletion causing immunodeficiency 3
• Oral thrush (candidiasis): A defining opportunistic infection that increases fourfold with HIV infection and correlates with CD4 counts below 200-350 cells/µL 4, 3
• Generalized lymphadenopathy: Present in >30% of HIV-seropositive patients, independent of CD4 count 3
• Constitutional symptoms: Weight loss and low-grade fever are common HIV-related manifestations that increase exponentially as CD4 counts decline 2, 3

Mechanism of CD4 T Cell Destruction

HIV specifically targets and destroys CD4 T cells through direct viral mechanisms:

• The CD4 antigen is an essential and specific component of the HIV receptor—the virus cannot infect cells without binding to CD4 1
• HIV binds to CD4 cell surface markers and destroys T lymphocytes expressing this receptor 5
• Productive infection with HIV markedly reduces cell-surface expression of CD4 1
• The immune system attempts to replenish CD4 T cells but cannot keep pace with viral destruction, leading to gradual disintegration of the CD4 T cell compartment 5

CD4 Count as Disease Marker

The net loss of CD4 T cells is the primary indicator for HIV disease progression and determines clinical management:

• CD4 counts guide staging, risk assessment for opportunistic infections, and need for prophylaxis 2
• Clinical manifestations like thrush, fever, and fatigue occur with CD4 counts of 400-700 cells/µL and increase exponentially with lower counts 3
• Advanced HIV disease is defined as CD4 count <50 cells/µL, requiring ophthalmologic evaluation for CMV retinitis 2
• CD4 counts <200 cells/µL or <14% define AIDS and necessitate prophylaxis against opportunistic infections 2

Why Not the Other Cell Types

• Macrophages: While HIV can infect macrophages, they are not the primary target cell destroyed by the virus 5
• B cells: Not directly targeted by HIV; B cell dysfunction is secondary to loss of CD4 T cell help
• Neutrophil precursor cells: Neutropenia can occur in HIV but is not the primary pathogenic mechanism 3

The CD4 T cell is unequivocally the key cell killed by HIV, and its progressive depletion is both the defining pathologic feature and the clinical predictor of disease progression in AIDS. 1, 3