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Snapshot
  • A 27-year-old man presents to the urgent care clinic with a 2-week history of fever, macular rash, and generalized lymphadenopathy. He denies a sore throat, genital ulcers, or urethral discharge. Sexual history is remarkable for having unprotected sex with both male and female partners while inconsistently using condoms. His last sexual encounter was a month prior to the onset of illness. His fourth-generation combination HIV-1/2 immunoassay is positive, and an HIV-1/HIV-2 antibody differentiation immunoassay confirms the diagnosis.
Introduction
  • Classification
    • a Lentivirus from the Retroviridae family
      • an enveloped, single-stranded, positive-sense RNA retrovirus 
  • Epidemiology
    • incidence
      • most commonly transmitted by sexual intercourse or sharing needles
    • HIV-2 is endemic to West Africa 
  • Transmission
    • sexual intercourse
    • sharing needles
    • vertical transmission from the mother to the fetus
  • Microbiology
    • genes 
      • env gene leads to the production of gp160, which is cleaved to produce gp120 and gp41
        • gp120 attaches to the patient's CD4+ T-cells 
        • gp41 leads to fusion and entry into the immune cell
      • gag gene leads to the production of p24 and p17 
        • p24 - viral capsid
        • p17 - viral matrix proteins
      • pol gene leads to the production of 
        • reverse transcriptase
        • aspartate protease 
        • integrase
  • Pathogenesis
    • HIV attaches to the surface of CD4+ T-cells, along with either CXCR4 or CCR5 coreceptor binding
      • HIV enters the cell, uncoats, and its RNA genome is reverse transcribed (by reverse transcriptase) into DNA
      • it integrates into the host's genome, creating billions of viral particles, lysing the host cell, and releasing the viral particles into the bloodstream infecting other CD4+ T-cells 
  • Associated conditions
    • opportunistic infections
    • malignancy
    • cognitive decline
    • cardiovascular disease
  • Prognosis
    • high mortality rate (> 90%) in untreated patients
Presentation
  • Symptoms/physical exam
    • acute retroviral syndrome
      • fever
      • lymphadenopathy
      • sore throat
      • rash
      • myalgia/arthralgia
      • weight loss
      • mucocutaneous ulcers
Studies
  • HIV serology  
    • fourth-generation combination HIV-1/2 immunoassay
      • best initial test
        • detects both
          • HIV-1 and HIV-2 antibodies
          • HIV p24 antigen 
        • approximate time frame for positive test post-infection: 15-20 days
      • interpretation
        • if negative
          • the patient is HIV-negative and no further test is needed
        • if positive
          • perform an HIV-1/HIV-2 antibody differentiation immunoassay
            • confirms the diagnosis
            • determines if the patient is infected with HIV-1, HIV-2, or both viruses
            • if the differentiation immunoassay is negative or indeterminate
              • perform a viral load
  • Viral load (qRT-PCR) 
    • used to determine the 
      • amount of virus the patient has
      • response to antiretroviral therapy
    • a high viral load is associated with a poor prognosis
    • approximate time frame for positive test post-infection: 10-15 days
  • CD4+ T-cell count and percentage
    • used to determine
      • need for prophylactic medication to prevent the development of opportunistic infections
      • response to antiretroviral therapy
  • HIV genotyping
    • used to determine HIV mutations that can lead to antiretroviral drug resistance
Opportunistic Infections
 
Opportunistic Infection Based on CD4+ T-Cell Count
CD4+ Count
Opportunistic Infection
Findings Prophylactic Treatment
< 500 mm3
  • Candida albicans
  • Oral thrush that is scrapable
  • Pseudohyphae on microscopy
-
   
  • Epstein-Barr virus
  • Oral hairy leukoplakia
    • not scrapable
  • HHV-8
  • Kaposi sarcoma 
    • a palpable, nonpruritic lesion that is brown, pink, red, or violaceous in color
  • HPV
  • Squamous cell carcinoma
    • anus (in men who have sex with men)
    • cervix
< 200 mm3
  • Histoplasma capsulatum
  • Nonspecific findings 
    • fevers, night sweats, chills, and weight loss
    • dyspnea
    • nausea and vomiting
  • Macrophages contain oval yeast cells
-
  • JC virus reactivation
  • Progressive multifocal leukoencephalopathy
    • demyelinating disease of the central nervous system
  • Pneumocystis jirovecii
  • Pneumonia
    • ground-glass opacity on chest radiography
  • Trimethoprim-sulfamethoxazole
    • if contraindicated, can give dapsone, atovaquone, or pentamidine
  • Cryptosporidium parvum
  • Watery diarrhea
  • Nitazoxanide 
< 100 mm3
  • Aspergillus fumigatus
  • Hemoptysis
  • Pleuritic chest pain
-
  • Bartonella henselae
  • Bacillary angiomatosis
    • angiomatous skin lesions
-
  • Candida albicans
  • Esophagitis 
    • white plaques may appear on endoscopy
-
  • Cytomegalovirus 
  • Retinitis
  • Esophagitis
  • Colitis
  • Pneumonitis
  • Encephalitis
  • Linear ulcers on endoscopy
  • Fundoscopy may demonstrate cotton-wool spots
  • Intranuclear inclusion bodies (owl eyes)
-
  • Cryptosporidium spp.
  • Watery diarrhea
  • Stool studies will show acid-fast oocysts
-
  • Ebstein-Barr virus
  • B-cell lymphoma
  • Central nervous system lymphoma
-
  • Mycobacterium avium-intracellulare 
  • Non-specific findings
    • fever
    • night sweats
    • weight loss
    • lymphadenitis
  • The goal is to initiate antiretroviral therapy as soon as possible
  • Azithromycin  
  • Toxoplasma gondii 
  • Ring-enhancing brain abscesses
  • Trimethoprim-sulfamethoxazole
    • if contraindicated, give dapsone, pyrimethamine, and leucovorin 
    • in the presence of ring-enhancing lesions, treat with pyrimethamine 
 
Differential
  • Influenza infection and immunosuppression caused by medications
    • differentiating factor
      • negative HIV screening tests
      • few to no risk factors for developing HIV (e.g., having sex without the use of barrier contraception and sharing needles)
Treatment
  • HIV-infected breastfeeding mothers
    • preferred to use replacement feedings due to high risk for transmission to the infant 
  • HIV-infected patients and vaccinations
    • HIV is an indication for obtaining the following vaccines
      • pneumococcal 
      • hepatitis B (if not already immune)
      • meningococcal
  • Medical
    • antiretroviral therapy
      • indication
        • first-line treatment for patients with HIV infection 
      • drug regimen
        • 2 nucleoside reverse transcriptase inhibitors (e.g., tenofovir alafenamide and emtricitabine) and an integrase inhibitor (e.g., bictegravir)
      • comments
        • the choice of antiretroviral drugs is guided by drug resistance testing
        • the most common cause of treatment failure is nonadherence
      • HIV-2 intrinisic resistance
        • non-nucleoside reverse transcriptase inhibitors (e.g., delavirdine efavirenz and nevirapine) and enfuvirtide (fusion inhibitor) 
        • regimen should utilize nucleoside reverse transcriptase inhibitors, integrase inhibitors, and protease inhibitors (e.g., lopinavir darunavir and saquinavir)
    • post-exposure prophylaxis
      • indication
        • first-line treatment given immediately after HIV exposure (such as in health care personnel)
          • initiate within 72 hours
      • drug regimen 
        • tenofovir, emtricitabine, and raltegravir
        • tenofovir, emtricitabine, and dolutegravir
    • pre-exposure prophylaxis
      • indication
        • to prevent HIV infection in high-risk patients
      • drug regimen
        • tenofovir and emtricitabine
    • antiretroviral therapy in pregnancy
      • indication
        • first-line treatment for pregnant women
      • comment
        • women who are pregnant are treated the same as for nonpregnant patients; however, certain medications should be avoided 
          • dolutegravir
          • elvitegravir
          • tenofovir alafenamide
      • intrapartum management  
        • HIV RNA ≤ 1000 copies/mL
          • mode of delivery
            • cesarean sections are not needed
        • HIV RNA > 1000 copies/mL
          • mode of delivery
            • if < 38 weeks, plan to perform a cesarean section at 38 weeks in order to prevent HIV exposure to the baby via rupture of membranes
          • drug regimen
            • intravenous zidovudine 
      • postpartum management
        • indication
          • all infants born to HIV-infected mothers
        • drug regimen
          • mothers with HIV RNA ≤ 1000 copies/mL
            • zidovudine in the infant for 4-6 weeks
          • mothers with HIV RNA > 1000 copies/mL
            • zidovudine, lamivudine, and nevirapine in the infant for 6 weeks
Complications
  • Malignancy
  • Cardiovascular and pulmonary disease
  • AIDS

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