Infectious Disease · HIV/AIDS
The facts most likely to be tested
The initial screening test for HIV is a fourth-generation antigen/antibody combination immunoassay that detects both HIV-1/2 antibodies and the p24 antigen.
A positive screening test must be confirmed with an HIV-1/HIV-2 antibody differentiation immunoassay to establish the diagnosis.
Pneumocystis jirovecii pneumonia (PJP) presents with diffuse interstitial infiltrates and an elevated LDH in patients with a CD4 count < 200 cells/mm³.
Toxoplasma gondii encephalitis manifests as multiple ring-enhancing lesions on brain imaging in patients with a CD4 count < 100 cells/mm³.
Cryptococcal meningitis is characterized by an elevated opening pressure on lumbar puncture and a positive cryptococcal antigen in the cerebrospinal fluid.
Cytomegalovirus (CMV) retinitis presents as hemorrhage and cotton-wool spots (pizza pie retinopathy) in patients with a CD4 count < 50 cells/mm³.
Mycobacterium avium complex (MAC) prophylaxis with azithromycin is indicated for patients with a CD4 count < 50 cells/mm³ who are not on effective antiretroviral therapy (ART).
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A 34-year-old male with a history of untreated HIV presents with a two-week history of progressive headache, confusion, and low-grade fever. Physical examination reveals mild nuchal rigidity. A lumbar puncture is performed, revealing an opening pressure of 28 cm H2O, a lymphocytic pleocytosis, and a positive India ink stain.
What is the most likely diagnosis?
Cryptococcal meningitis
The patient's presentation of elevated opening pressure and positive India ink stain in the setting of advanced HIV is pathognomonic for cryptococcal meningitis, which is tested as a high-yield opportunistic infection in patients with CD4 counts < 100.
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High yield triage
Etiology / Epidemiology
Transmitted via unprotected sexual contact, IV drug use, and vertical transmission. High-risk groups include MSM and those with multiple sexual partners.
Clinical Manifestations
Acute retroviral syndrome mimics mononucleosis. AIDS defined by CD4 < 200 or AIDS-defining illnesses.
Diagnosis
Screen with 4th generation HIV-1/2 antigen/antibody immunoassay. Confirm with HIV-1/2 antibody differentiation immunoassay.
Treatment
Initiate Tenofovir/Emtricitabine + Dolutegravir (or Bictegravir) immediately. Do not delay ART.
Prognosis
Monitor viral load and CD4 count. Goal is undetectable viral load to prevent transmission.
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Epidemiology & Etiology
HIV is a retrovirus targeting CD4+ T-lymphocytes. Primary transmission occurs via exchange of blood, semen, vaginal secretions, or breast milk. IV drug use and unprotected intercourse remain the leading risk factors in the US.
Pertinent Anatomy
The virus targets cells expressing the CD4 receptor and CCR5 or CXCR4 co-receptors. Depletion of these cells leads to profound cellular immunodeficiency.
Pathophysiology
Viral entry involves binding to CD4 receptors, followed by reverse transcription of viral RNA into DNA. Integration into the host genome leads to chronic infection. Progressive CD4 cell destruction results in the clinical state of AIDS.
Clinical Manifestations
Acute infection presents with flu-like symptoms, lymphadenopathy, and a maculopapular rash. AIDS-defining conditions include Pneumocystis jirovecii pneumonia, Kaposi sarcoma, and esophageal candidiasis. Weight loss and chronic diarrhea are red flags for advanced disease.
Diagnosis
The 4th generation antigen/antibody immunoassay is the gold standard for screening. Positive results require a HIV-1/2 antibody differentiation immunoassay for confirmation. Nucleic acid testing (NAT) is used to resolve discordant results or detect acute infection.
Treatment
Standard of care is Tenofovir/Emtricitabine + Dolutegravir. Abacavir requires HLA-B*5701 testing to prevent hypersensitivity. Prophylaxis for opportunistic infections is required when CD4 < 200 (TMP-SMX for PCP).
Prognosis
Patients must achieve an undetectable viral load to prevent progression and transmission. Regular monitoring of CD4 count and viral load is essential to assess treatment efficacy. Non-adherence leads to rapid resistance.
Differential Diagnosis
Mononucleosis: heterophile antibody positive
CMV: retinitis with 'pizza pie' appearance
Toxoplasmosis: ring-enhancing brain lesions
Cryptococcal meningitis: elevated opening pressure
Mycobacterium avium complex: CD4 < 50