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Snapshot
  • A 36-year-old woman is admitted to a hospital in India with a three-week history of fever, headache, and increasing drowsiness. Past medical history reveals she was diagnosed with pulmonary TB nine months ago. She is in the continuation phase of her anti-TB regimen. On exam, patient is pale and emaciated. There are coarse crackles in both lung fields. She is disoriented to time, person, and place but responds to commands. Kernig sign is positive. A complete blood count revealed a hematocrit of 30%, WBC of 12,500 cells/mm3, with 84% neutrophils. Urinalysis, basic metabolic profile, and liver function tests were within normal limits. Sputum for AAFB was negative. A HIV screen was positive and this was confirmed with a Western blot. CD4 count was 57 cells/μL. Fundoscopy was normal. Chest radiograph revealed bilateral opacities in both lung fields. CT scan of the brain was normal. CSF analysis revealed lymphocytes 64 cells/mm3, protein 84mg/dL and glucose 31 mg/dL. Gram and Ziehl-Neelsen stains were negative. CSF for India ink stain was positive for Cryptococcus neoformans.
Introduction
  • Classification
    • (+) ssRNA retrovirus
      • HIV
Presentation
  • CD4 < 400 cells/μL 
    • constitutional symptoms ("wasting syndrome")
      • weight loss
      • fever
      • night sweats
      • adenopathy
    • bacterial infections
      • M. tuberculosis
      • H. influenzae
      • S. pneumoniae
      • Salmonella
      • Nocardia may cause TB-like pulmonary cavitations 
    • oral thrush (Candida albicans)
    • tinea pedis
    • reactivation VZV
  • CD4 < 200 cells/μL 
    • PCP (Pnuemocystis jiroveci pneumonia)
    • Cryptococcus neoformans
    • Cryptosporidium
    • Coccidioidomycosis
    • reactivation HSV
    • Iospora
  • CD4 < 100 cells/μL
    • Toxoplasma gondii 
      • when patient presents with neurological findings
        • next best step is imaging of the head (CT or MRI)
      • if ring enhancing lesion is present
        •  the next best step is empiric treatment with pyrimethamine-sulfadiazine
      • if treatment fails, biopsy of lesion is necessary
    • Histoplasmosis
    • Candida albicans esophagitis
      • Candida is the most common cause of esophagitis in late HIV undefined
    • Kaposi Sarcoma
      • eruption of violaceous plaques Skin lesions of Kaposi Sarcoma
      • could be indicative of HIV
      • more common in men who have sex with men
  • CD4 < 50 cells/μL blood
    • M. avium-intracellulare  
    • CMV
      • retinitis and esophagitis
    • Cryptococcus neoformans
      • meningoencephalitis
  • HIV in the neonate (a ToRCHeS infection)
    • recurrent infections
      • oral thrush
      • interstitial pneumonia
    • chronic diarrhea
    • lymphopenia
  • HIV encephalitis
    • HIV crosses BBB via infected macrophages
    • results in inflammation in the brain
      • appearance of microglial nodules with multinucleated giant cells
    • occurs late in the course of HIV infection
  • AIDS dementia complex
    • mental status changes
    • depression
    • ataxia
    • seizures
    • urinary and bowel incontinence
  • Serous otitis media 
    • from obstructive lympadenopathy/lymphomas
Evaluation
  • Diagnosis of HIV
    • ELISA is the first step in diagnosis
      • high false-positive rate (high sensitivity and low specificity)
      • rules OUT the possibility of infection
    • HIV 1/2 differentiation assay 
      • best confirmatory test
      • returns result more quickly than a Western blot
    • Western blot is then used to confirm positive results
      • high false-negative rate (low sensitivity and high specificity)
      • rules IN the diagnosis of infection
    • Both tests detect antibodies to HIV proteins
      • antibodies take 3-6 weeks to develop
      • tests can be falsely negative in first 1-2 months of infection
      • tests can be falsely positive in babies born to infected mothers
        • anti-gp120 crosses placenrta
    • the presence of viral RNA or antigens (e.g. p24) can also be tested directly
  • Diagnosis of AIDS
    •  CD4+ ≤ 200 cell/ul (normal: 500-1500 cells/ul)
    • CD4+ percentage <14%
    • HIV positive with AIDS-associated infection
      • e.g., P. jiroveci pneumonia
  • Viral load tests
    • PCR used to monitor effects of therapy on viral load
    • high viral load associated with poor prognosis
Differential
  • Other causes of immune suppresion
    • cancer chemotherapy
    • organ transplant patients
    • congenital immuonodeficiencies
Treatment
  • Over 25 HIV drugs exist in multiple categories
    • CCR5 inhibitors
    • fusion inhibitors
    • reverse transcriptase inhibitors
    • integrase inhibitors
    • protease inhibitors
  • Highly active antiretroviral therapy (HAART)
    • combines multiple drugs with multiple mechanisms of action to prevent resistance
      • e.g., tenofovir + emtricitabine + efavirenz or many other possible combinations
  • Pregnancy
    • use zidovudine (ZDV and AZT) to prevent mother-to-fetus transmission 
    • efavirenz and delavirdine are thought to be teratogenic 
    • HIV is an absolute contraindication to breastfeeding in the United States  
Prognosis, Prevention,  and Complications
  • Prognosis
    • has improved but depends on multiple factors
      • most important access to proper drug treatment
    • poor prognostic factors include
      • high viral RNA loads
      • CD4 count < 200 cells/μL 
  • Prevention 
    • no effective HIV vaccine available
      • for exposure: obtain HIV serology and immediately initiate three-drug antiretroviral therapy 
    • vaccination against secondary infection
      • pneumococcal vaccine is indicated in HIV-positive patients 
      • live vaccines are contraindicated in HIV-positive patients
        • MMR and Varicella can be given IF CD4 count is >200 cells/μL blood
    • secondary prevention involves prevention of opportunistic infection
      • CD4 count used to determine need for prophylaxis
        • < 200 cells/μL TMP-SMX for Pneumocystis pneumonia
        • < 100 cells/μL TMP-SMX for toxoplasmosis
        • < 50 cells/μL azithromycin for M. avium-intercellulare
  • Complications
    • may be due to HIV infection or side effects of HAART
      • dyslipidemia
      • glucose intolerance/diabetes mellitus
      • cardiovascular disease
  •  
 

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