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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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(M1.MC.15.75) A 44-year-old male presents to the emergency department with complaints of productive cough, fevers, shortness of breath, and increasing fatigue over the last 2 weeks. He also reports several episodes of diarrhea and occasional abdominal pain. His medical history is significant for a diagnosis of HIV infection 10 years ago and Pneumocystis jiroveci pneumonia 4 years ago. The patient reports that he stopped taking his anti-retroviral medications 9 months ago. Vital signs are as follows: T 38.2, HR 86, BP 132/87, RR 16, SpO2 96%. Physical examination is significant for generalized wasting, pale appearing skin and conjunctiva, and crackles auscultated over the left lung field. A chest radiograph is obtained and is shown in Figure A. A CD4 count reveals 27 cells/uL. Blood cultures are drawn and ultimately show acid-fast bacilli. A quantiferon-gold TB test returned negative for Mycobacterium tuberculosis. Prophylaxis with which of the following could have prevented this patient's current illness?

QID: 106834
FIGURES:
1

Isoniazid

19%

(49/260)

2

Pneumococcal vaccination

8%

(21/260)

3

Trimethoprim-sulfamethoxazole

30%

(79/260)

4

Azithromycin

41%

(106/260)

5

Hepatitis B vaccination

1%

(2/260)

M 3 D

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(M1.MC.14.19) For which of the following patients would you recommend prophylaxis against mycobacterium avium-intracellulare?

QID: 100822
1

22-year old HIV positive female with CD4 count of 750 cells/ microliter and a viral load of 500,000 copies/mL

6%

(4/70)

2

30-year old HIV positive male with CD4 count of 20 cells/ microliter and a viral load of < 50 copies/mL

56%

(39/70)

3

45-year old HIV positive female with CD4 count of 250 cells/ microliter and a viral load of 100,000 copies/mL

16%

(11/70)

4

50-year old HIV positive female with CD4 count of 150 cells/ microliter and a viral load of < 50 copies/mL

16%

(11/70)

5

36-year old HIV positive male with CD4 count of 75 cells/microliter and an undetectable viral load.

6%

(4/70)

M 3 B

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(M1.MC.13.29) A 23-year-old male with a homozygous CCR5 mutation is found to be immune to HIV infection. The patient’s CCR5 mutation interferes with the function of which viral protein?

QID: 101488
1

Reverse transcriptase

5%

(5/105)

2

gp120

76%

(80/105)

3

gp41

14%

(15/105)

4

p24

4%

(4/105)

5

pp17

1%

(1/105)

M 1 E

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(M1.MC.13.63) A newborn male presents to the emergency room with a fever and the oropharyngeal findings shown in Figure A. The patient's mother reports that he also has chronic diarrhea, and laboratory workup shows lymphocytopenia. During a careful review of the social history, you learn that the mother has a history of IV drug abuse and commercial sex work. She was prescribed prenatal medications, but failed to take one of them as directed. Which of the following may have helped prevent this patient's condition?

QID: 101522
FIGURES:
1

Folic acid

5%

(3/58)

2

Acyclovir

10%

(6/58)

3

Zidovudine

69%

(40/58)

4

Ribavirin

7%

(4/58)

5

Zanamivir

3%

(2/58)

M 3 E

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