Updated: 6/2/2021

Human Immunodeficiency Virus (HIV)

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Snapshot
  • A 44-year-old man presents to his primary care physician for 1 week of worsening malaise, myalgias, sore throat, and chills. He denies any sick contacts or recent travel history. His past medical history is noncontributory. He drinks alcohol occasionally, denies smoking, and is sexually active with 2 men and inconsistently uses condoms. In the past, he has been treated for chlamydia and gonorrhea. He consents for a fourth-generation combination HIV-1/2 immunoassay, which returns positive. An HIV-1/HIV-2 antibody differentiation immunoassay confirms the diagnosis and he is started on tenofovir alafenamide, emtricitabine, and bictegravir.
Introduction
  • Definition
    • a blood-borne virus that is transmitted via
      • sexual intercourse
      • sharing needles
      • vertical transmission from the mother to the fetus
  • Epidemiology
    • incidence
      • most commonly transmitted by sexual intercourse or sharing needles
  • Microbiology
    • enveloped virus
    • single-stranded positive-sense RNA retrovirus
    • 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 is reverse transcribed (by reverse transcriptase) into DNA, which 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
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 of the
    • anus (in men who have sex with men)
    • cervix
< 200 mm3
  • Histoplasma capsulatum
  • Nonspecific findings such as
    • 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 
    • focal neurologic deficits
    • ring enhancing lesion on brain MRI
    • EBV+ in CSF PCR
-
  • 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  
 
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
      • screening criteria 
        1. at least once for all patients age 15 to 65 regardless of risk factors
        2. men who have sex with men
        3. pregnant women
        4. IV drug users
        5. patients who engage in unprotected sex
        6. those diagnosed with another sexually transmitted disease (STD)
      • 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
  • 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
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
    • 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
  • HIV-associated dementia
    • cognitive deficits, behavioral changes, and diminished motor skills not attributable to another cause
    • cortical atrophy and symmetric, periventricular white matter lesions on T2-weighted MRI 
  • Immune reconstitution inflammatory syndrome
    • results in paradoxical worsening of infectious symptoms due to immune recovery from antiretroviral therapy
      • treatment involves continuing antiretroviral therapy and symptomatic treatment (e.g., acetaminophen and a short course of steroids)
 

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Questions (19)
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(M2.ID.17.4694) A 33-year-old man is brought into the emergency department with fever, lethargy, and confusion. He is a cachectic man in acute distress, unable to respond to questions or follow commands. His friend confides that the patient has been sexually active with multiple male partners and was diagnosed with HIV several months ago, but was lost to follow up. Based on prior records, his most recent CD4 count was 65 cells/uL. Which of the following is the most appropriate next step in management?

QID: 107880
1

Recheck CD4 and HIV viral load serologies

0%

(0/2)

2

Lumbar puncture

0%

(0/2)

3

MRI brain with contrast

0%

(0/2)

4

CT head without contrast

0%

(0/2)

5

Neurological exam with fundoscopy

50%

(1/2)

M 6 B

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(M2.ID.17.4867) An 87-year-old man presents to the emergency department with decreased hearing. The patient states that for the past week he has had decreased hearing that is predominantly affecting his left ear. He denies any fever, chills, nausea, vomiting, or changes in his vision. The patient has a past medical history of asthma, HIV, and anxiety. His current medications include HAART, albuterol, and clonazepam. The patient states his last CD4 count taken 2 weeks ago was 650. His temperature is 99.5°F (37.5°C), blood pressure is 127/68 mmHg, pulse is 100/min, respirations are 11/min, and oxygen saturation is 98% on room air. Laboratory values are obtained and shown below:

Hemoglobin: 11 g/dL
Hematocrit: 33%
Leukocyte count: 2,500/mm^3 with normal differential
Platelet count: 197,000/mm^3

Serum:
Na+: 139 mEq/L
Cl-: 100 mEq/L
K+: 4.3 mEq/L
HCO3-: 24 mEq/L
BUN: 20 mg/dL
Glucose: 99 mg/dL
Creatinine: 1.1 mg/dL
Ca2+: 10.2 mg/dL
AST: 12 U/L
ALT: 10 U/L

On physical exam, you note an elderly man in no current distress. Cardiopulmonary exam is within normal limits. HEENT exam reveals the finding in Figure A but is otherwise unremarkable. Neurological exam reveals decreased hearing in the patient's left ear but is otherwise non-focal. On otoscopy, the tympanic membrane is hypomobile. Which of the following is the most appropriate next step in management?

QID: 109654
FIGURES:
1

CT scan of the head

0%

(0/1)

2

Tympanocentesis

100%

(1/1)

3

Amoxicillin

0%

(0/1)

4

Amoxicillin-clavulanic acid

0%

(0/1)

5

Supportive therapy and outpatient referral

0%

(0/1)

M 7 D

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(M2.ID.17.4732) A 46-year-old Caucasian male with past medical history of HIV (CD4: 77/mm^3), hypertension, hyperlipidemia, and osteoarthritis presents to the emergency department with sudden weakness of his right hand. He reports that the weakness has gradually been getting worse and that this morning he dropped his cup of coffee. He has never had anything like this happen to him before, although he was hospitalized last year for pneumonia. He reports inconsistent adherence to his home medications, which include raltegravir, tenofovir, emtricitabine, TMP-SMX, hydrochlorothiazide, pravastatin, and occasional ibuprofen. His father died of a myocardial infarction at the age of 60, and his mother suffered a stroke at the age of 72. The patient's temperature is 102.6°F (39.2°C), blood pressure is 156/92 mmHg, pulse is 88/min, and respirations are 18/min. On neurological exam, he has 3/5 strength in the distal muscles of the right extremity with preserved sensation. His neurological exam is normal in all other extremities.

Which of the following is the best next step in management?

QID: 108600
1

Lumbar puncture

8%

(5/62)

2

Serology for Toxoplasma-specific IgG antibodies

5%

(3/62)

3

Head CT

68%

(42/62)

4

Empiric treatment with pyrimethamine-sulfadiazine

19%

(12/62)

5

Empiric treatment with itraconazole

0%

(0/62)

M 6 D

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(M3.ID.15.9) A 27-year-old G2P1 woman is diagnosed with an HIV infection after undergoing routine prenatal blood work testing. Her estimated gestational age by first-trimester ultrasound is 12 weeks. Her CD4 count is 150 cells/mm^3 and her viral load is 126,000 copies/mL. She denies experiencing any symptoms of HIV infection. Which of the following is appropriate management of this patient's pregnancy?

QID: 102539
1

Avoidance of antibiotic prophylaxis

0%

(0/16)

2

Breastfeeding

0%

(0/16)

3

HAART

19%

(3/16)

4

HAART after delivery

81%

(13/16)

5

Vaginal delivery

0%

(0/16)

M 11 E

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(M2.ID.15.11) A 33-year-old HIV-positive male is seen in clinic for follow-up care. When asked if he has been adhering to his HIV medications, the patient exclaims that he has been depressed, thus causing him to not take his medication for six months. His CD4+ count is now 33 cells/mm3. What medication(s) should he take in addition to his anti-retroviral therapy?

QID: 104896
1

Fluconazole

7%

(2/28)

2

Dapsone

0%

(0/28)

3

Azithromycin and trimethoprim-sulfamethoxazole

68%

(19/28)

4

Azithromycin and fluconazole

7%

(2/28)

5

Azithromycin, dapsone, and fluconazole

11%

(3/28)

M 7 E

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(M2.ID.12.2) A 32-year-old HIV positive female known to be non-adherent to her treatment regimen, presents to the hospital with the complaint of new-onset headaches. Her vital signs are only significant for a low-grade fever. Neurological examination reveals right-sided upper motor neuron signs, as well as a inattention and difficulty with concentration. The patient currently does not have a primary medical provider. A CT of the patients head is shown in the image below. What is the next best step in management for this patient?

QID: 104887
FIGURES:
1

Perform a biopsy of the lesion

4%

(4/92)

2

Perform an analysis for 14-3-3 protein levels

3%

(3/92)

3

Begin treatment with pyrimethamine-sulfadiazine

72%

(66/92)

4

Begin treatment with albendazole and corticosteroids

13%

(12/92)

5

Begin treatment with acyclovir

7%

(6/92)

M 7 C

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