Updated: 1/9/2019

Human Immunodeficiency Virus (HIV)

Topic
Review Topic
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Questions
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Evidence
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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 undefined
    • 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
 
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
      • 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
 

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Questions (17)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
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(M2.ID.10) A 31-year-old male presents to the emergency department complaining of difficulty eating and pain with swallowing. He reports that the problem started yesterday, although he has been feeling weak for the past 8 months. Physical exam reveals a thin man in no acute distress and is otherwise unremarkable. Laboratory studies show a CD4+ count of 56 cells/microL. Which of the following is the most likely cause of this patient's dysphagia? Review Topic

QID: 104895
1

Acute HIV

5%

(2/44)

2

Pneumocystis jiroveci (P. carinii)

0%

(0/44)

3

Candida

77%

(34/44)

4

HSV

5%

(2/44)

5

CMV

11%

(5/44)

M2

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(M3.ID.9) A 27-year-old G2P1 female 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 550 cells/mm^3 and her viral load is 26,000 copies/mL. She denies experiencing any symptoms of HIV infection. Which of the following highly active antiretroviral therapy (HAART) medications should be avoided in this patient? Review Topic

QID: 102539
1

Nelfinavir

0%

(0/13)

2

Zidovudine

0%

(0/13)

3

Lamivudine

0%

(0/13)

4

Efavirenz

100%

(13/13)

5

Ritonavir

0%

(0/13)

M2

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(M2.ID.7) A 29-year-old woman presents to her obstetrician for her first prenatal visit. Screening tests reveal that she is HIV-positive, and her CD4 count is 550. What is the best course of action to prevent mother-to-child transmission? Review Topic

QID: 104892
1

No treatment

0%

(0/4)

2

HAART for Mom during pregnancy if CD4 count falls below 500; Zidovudine for neonate for 6 wks postpartum

0%

(0/4)

3

HAART for Mom during labor and delivery; Zidovudine for neonate for 6 wks postpartum

50%

(2/4)

4

HAART for Mom during pregnancy; Zidovudine for neonate for 6 wks postpartum

50%

(2/4)

5

HAART for Mom during pregnancy; no treatment for neonate after birth

0%

(0/4)

M2

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(M2.ID.12) A 29-year-old male with HIV presents to his primary care physician with fevers, night sweats, weight loss, and a cough productive of yellow sputum for 2 months. The patient was found to have a negative PPD and treated with azithromycin in an urgent care clinic 1 month ago. The patient's chest radiograph is shown in Image A. An acid-fast stain of the patient's sputum is performed with the results shown in Image B. Which of the following infectious agents is most likely responsible for this patient's presentation? Review Topic

QID: 104897
FIGURES:
1

Streptococcus pneumoniae

7%

(6/83)

2

Legionella pneumophilia

2%

(2/83)

3

Mycobacterium tuberculosis

41%

(34/83)

4

Nocardia asteroides

37%

(31/83)

5

Actinomyces israelii

8%

(7/83)

M2

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(M2.ID.3) A 26-year-old HIV positive male presents to his primary care physician for routine care. The patient has not seen a healthcare provider in 2 years and at this visit his CD4 count is found to be 105 cells/mm^3. He has never had chicken pox. He plans to travel to Africa next month. Which of the following vaccines is indicated for this patient? Review Topic

QID: 105640
1

Pneumococcal polysaccharide vaccine

74%

(45/61)

2

Varicella zoster virus vaccine

8%

(5/61)

3

Live attenuated influenza vaccine

3%

(2/61)

4

Live oral poliovirus vaccine

0%

(0/61)

5

Yellow fever vaccine

11%

(7/61)

M2

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PREFERRED RESPONSE 1
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Topic COMMENTS (23)
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