7.1 Viral Infections (HIV, EBV, Influenza)

7.1 Viral Infections (HIV, EBV, Influenza)

Why This Matters for the PANCE

Viral infections are a high-yield component of the PANCE blueprint, representing common acute and chronic pathologies in primary care and emergency departments. Candidates must master:

• HIV stages, diagnostic algorithm, CD4 thresholds, and prophylactic regimens for major opportunistic infections (PCP, Toxoplasmosis, and MAC).
• Epstein-Barr Virus (EBV) clinical presentation, atypical lymphocytes, splenic rupture, and contact sports restrictions.
• Influenza pathophysiology (drift vs. shift), diagnostic testing, and the clinical indications and timing of neuraminidase inhibitors.

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HIV & AIDS

Pathophysiology & Stages

HIV is an enveloped retrovirus that infects CD4+ helper T cells, macrophages, and dendritic cells. The envelope glycoprotein gp120 binds to the host CD4 receptor and a co-receptor (CCR5 or CXCR4), while gp41 facilitates membrane fusion. Once inside, reverse transcriptase converts viral RNA into DNA, which integrase integrates into the host genome, leading to progressive CD4+ cell destruction.

1. Acute HIV Infection: Occurs 2–4 weeks post-exposure. Presents as a mononucleosis-like illness with fever, generalized lymphadenopathy, sore throat, maculopapular rash, and myalgias. Viral replication is extremely high.
2. Chronic HIV Infection: Often asymptomatic clinical latency lasting years.
3. AIDS: Defined by a CD4 count < 200 cells/uL OR the presence of an AIDS-defining condition (e.g., esophageal candidiasis, PCP, Kaposi sarcoma, cryptococcal meningitis).

Opportunistic Infection (OI) CD4 Thresholds

Prophylaxis is initiated based on CD4 count thresholds to prevent opportunistic infections:

[!IMPORTANT] Modern Guideline Update: Primary prophylaxis for MAC is no longer routinely recommended if the patient immediately initiates Antiretroviral Therapy (ART), as rapid CD4 recovery effectively minimizes MAC risk.

Diagnostics & Management

1. Screening: HIV-1/2 antigen/antibody combination immunoassay (detects HIV-1/2 antibodies and p24 antigen).
2. Confirmatory Testing: HIV-1/2 antibody differentiation immunoassay if screening is reactive.
3. Viral Load: HIV-1 RNA nucleic acid test (NAT) if the differentiation assay is indeterminate, detecting acute infection.

• ART Principles: Initiated immediately upon diagnosis. First-line is a 3-drug regimen: 2 NRTIs (e.g., Tenofovir/Emtricitabine) PLUS 1 INSTI (e.g., Dolutegravir or Bictegravir).
• PANCE Pearls: Screen for the HLA-B*5701 allele prior to starting Abacavir due to the risk of a fatal systemic hypersensitivity reaction. Tenofovir Disoproxil Fumarate (TDF) is linked to nephrotoxicity and osteopenia; Tenofovir Alafenamide (TAF) is a safer alternative.

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Epstein-Barr Virus (EBV) & Infectious Mononucleosis

Clinical Presentation & Diagnostics

EBV is a Herpesvirus (HHV-4) transmitted via saliva. It infects B lymphocytes by binding to the CD21 receptor. Cytotoxic CD8+ T cells respond to control the infection, presenting as atypical lymphocytes. The classic clinical triad includes fever, tonsillar pharyngitis (severe, with thick white exudates), and posterior cervical lymphadenopathy (symmetric, tender). Splenomegaly (50%) and fatigue are common.

• Diagnostics:
  • Smear: Atypical lymphocytes (Downey cells), which are reactive CD8+ T cells with indented cytoplasm.
  • Heterophile Antibody Test (Monospot): Agglutination assay. Specific, but can be negative in the first week or in children < 4.
  • Serology: IgM anti-VCA (acute) and IgG anti-EBNA (past infection).

Clinical Management & PANCE Pearls

• Splenic Rupture Risk: Patients must avoid contact sports, strenuous exercise, and heavy lifting for a minimum of 3 to 4 weeks from symptom onset. Spleen size should be clinically normal before clearance.
• Amoxicillin Rash: Treating mono patients with amoxicillin or ampicillin causes a classic, non-allergic, maculopapular rash. This does not indicate a true penicillin allergy.

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Influenza

Pathophysiology & Presentation

Influenza is a single-stranded RNA virus transmitted via respiratory droplets. Surface glycoproteins Hemagglutinin (HA) mediates viral entry, and Neuraminidase (NA) facilitates release.

• Antigenic Drift: Minor point mutations in HA/NA causing seasonal epidemics (occurs in Influenza A and B).
• Antigenic Shift: Major genetic reassortment creating completely new HA/NA proteins, leading to global pandemics (occurs only in Influenza A).
• Symptoms: Abrupt onset of high fever, myalgias, headache, non-productive cough, sore throat, and fatigue.

Diagnostics & Management

• Testing: Rapid Antigen Tests (RIDTs) have high specificity but moderate sensitivity (50-70%; a negative test does not rule out flu). RT-PCR is the gold standard.
• Pharmacotherapy: Neuraminidase inhibitors like Oseltamivir (Tamiflu) block viral release. Most effective when started within 48 hours of symptom onset (reduces duration by 1–1.5 days). Initiate after 48 hours only if the patient is hospitalized, has progressive illness, or is at high risk (adults ≥ 65, children < 2, pregnancy, or chronic cardiorespiratory/metabolic disease).
• Secondary Bacterial Pneumonia: Suspect if a patient improves and then suddenly deteriorates with high fever, productive cough, and dyspnea (commonly S. pneumoniae or S. aureus including MRSA).