Human Immunodeficiency Virus (HIV) - Infectious Dis.

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	-
	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

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

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