Hiv/Aids

[Section Outline]

Signs and Symptoms
Essential Workup
Diagnostic Tests & Interpretation
Differential Diagnosis

Signs and Symptoms

Primary HIV infection: 2-6 wk after exposure:
- Fever and malaise
- Rash on face and trunk
- Flu-like syndrome with lymphadenopathy and hepatosplenomegaly
- Pharyngitis
- Diarrhea
- Up to 90% asymptomatic
Advanced HIV disease (CD4 <200):
- Fatigue
- Fevers and night sweats
- Weight loss/wasting
- Alopecia
- Chronic diarrhea
- Cough
- Dyspnea
- Hemoptysis
- Chronic low-grade headache
- Altered mental status
- Seizures
- Dementia
- Neuropathy
- Painless visual loss
- Skin lesions

History

Risk factors:
- Multiple sexual partners
- IV drug abuse
- Men who have sex with men
- Blood transfusions prior to 1985
- Unprotected sex with at-risk partners
- Uncircumcised
Most recent CD4 count and viral load, lowest CD4 count
History of or current use of antiretroviral medications
Medication compliance
Length of diagnosis/illness
History of opportunistic infections
Previous hospitalizations or ICU admissions

Essential Workup

The window period during which diagnostic tests may be negative depends on the diagnostic test used:
- DNA amplification can be positive within 1-2 wk
- Protein P24 can be detected within 15 d
- Serum antibody testing will require at least 20 d for detection
- POCT/rapid HIV testing: Using oral swabs or finger stick blood:
  - Lab serum tests have greater sensitivity for acute HIV infection
Respiratory symptoms:
- Chest radiograph
- Arterial blood gas (ABG)
- Sputum for Gram stain, AFB, and culture
- Serum LDH - elevated in PJP
- Blood cultures
Cardiac symptoms:
- Serum cardiac markers, electrolytes
- CXR
- ECG in cases of suspected pericarditis, effusion, or tamponade
- Blood cultures if endocarditis is suspected
- Drug screen for cocaine and amphetamines
Neurologic symptoms:
- Head CT with and without contrast
- Lumbar puncture with opening pressure
- CSF for glucose, protein, Gram stain and culture, cell count with differential, AFB smear, India ink stain, herpes simplex and cryptococcus antigen, and VDRL
GI symptoms:
- Stool for ova and parasites, Gram stain, culture, and Clostridium difficile assay
- Urine analysis
- For women: Urine pregnancy test, pelvic exam with wet mount, and gonorrhea/chlamydia testing
- Liver functions tests, amylase, and lipase
- Hepatitis serologies
- Low threshold for CT abdomen/pelvis
- US if biliary symptoms present
- Low threshold for surgical consult, as HIV patients may not present with classic acute abdomen
Fever workup:
- Include aerobic/anaerobic, fungal, AFB, and MAC blood cultures
Ocular symptoms:
- Fluorescein staining with slit lamp exam

Diagnostic Tests & Interpretation

Lab

ELISA:
- Detects IgG antibody against HIV
- Sensitivity and specificity ∼99%
Western blot: Is no longer recommended by the CDC as part of the testing algorithm
Initial testing should be done with a fourth generation antigen-antibody combination assay to screen for infection:
- Can detect HIV-1, HIV-2 antibodies, and HIV-1 p24 antigen
- Allows for earlier detection
- No further testing required if negative
- If positive, an antibody immunoassay is used to differentiate between HIV-1 and HIV-2
- Those that are nonreactive or indeterminate in the antibody differentiation immunoassay should undergo a nucleic acid test for confirmation
Absolute lymphocyte count (ALC):
- Multiply WBC × percent lymphocytes
- If ALC >2,000, likely CD4 >200, if ALC <1,000, likely CD4 <200

Imaging

CXR:
- Bilateral interstitial infiltrates: PJP
- Reticulonodular infiltrates: TB, KS, or fungal pneumonia
- Hilar lymphadenopathy with infiltrate: TB, cryptococcosis, histoplasmosis, neoplasm
- Lobar consolidation: Bacterial pneumonia
- Cavitation: TB, necrotizing bacterial pneumonia, coccidioidomycosis
- Normal x-ray does not rule out PJP or TB
Head CT with and without IV contrast:
- Multiple ring-enhancing lesions with edema in basal ganglia or cortex: Toxoplasmosis or CNS lymphoma
- Subcortical nonenhancing lesions: PML
Abdominal/pelvic CT:
- Splenomegaly: CMV, TB
- Intestinal perforation or bowel obstruction: CMV colitis, lymphoma, histoplasmosis, MAC, appendicitis, ulcer disease, KS
- Cholecystitis or cholangitis: Cryptosporidium, Microsporidium, CMV
- Pancreatitis: Medication-related, neoplasm, infectious

Differential Diagnosis

For pulmonary symptoms with HIV:
- Pulmonary emboli
- Pulmonary HTN
- TB
- Pneumonia: Bacterial, fungal, viral
- Pulmonary malignancies
- Lymphocytic interstitial pneumonitis
For CNS symptoms with HIV:
- Neurosyphilis
- CMV or HSV encephalitis
- Toxoplasmosis
- CNS lymphoma
- Meningitis (bacterial, coccidioidal, etc.)
- Subarachnoid hemorrhage
- Cerebral infarction
- HIV or metabolic encephalitis
- Progressive multifocal leukoencephalopathy
Cardiac symptoms with HIV:
- Cardiomyopathy
- Pericarditis/myocarditis
- Endocarditis
- Acute coronary syndrome
- Pericardial effusion
Oral symptoms with HIV:
- Fungal infection (i.e., cand idiasis)
- Viral lesions (HSV, CMV, hairy leukoplakia)
- Bacterial lesions (TB, periodontal disease)
- Autoimmune (salivary gland disease, aphthous ulcers)
- Neoplasm (KS, lymphoma)
Esophageal symptoms with HIV:
- Infectious esophagitis (cand ida, CMV, HSV)
- Reflux esophagitis
Diarrhea with HIV:
- Medication side effect
- Parasites (Cryptosporidium, Giardia, Isospora)
- Bacteria
- Viral (CMV, HSV, HIV)
- Fungi (histoplasmosis, cryptococcus)
- HIV-associated enteropathy
Hepatomegaly with HIV:
- Hepatitis
- Opportunistic infection (CMV, MAC, TB)
Renal disease with HIV:
- Drug nephrotoxicity
- HIV nephropathy
- Vasculitis
- Obstruction

Treatment ⬆ ⬇

[Section Outline]

ED Treatment/Procedures
Medication

ED Treatment/Procedures

Patients who appear to have bacterial infections, appear toxic, or have rapidly progressive symptoms should receive their first dose of antibiotics in the ED
Begin HIV treatment if: Low CD4 (<350) or high viral load, pregnancy, AIDS defining illness or HIV-associated nephropathy (in general, patients with documented primary HIV infection also undergo resistance testing after the diagnosis has been established)
Triple therapy (HAART):
- 1 nonnucleoside reverse transcriptase inhibitors (NNRTI) and 2 nucleoside reverse transcriptase inhibitors (NRTI)
- 1 PI and 2 NRTIs
- Triple NRTI
Postexposure prophylaxis PEP:
- Start therapy within 2 hr if possible and continue for 4 wk
- Not recommended >72 hr after exposure
- 3-drug regimen recommended for most exposures:
  - Tenofovir + emtricitabine + raltegravir or dolutegravir
Pre - exposure prophylaxis PrPEP
- Consider for: MSM, those in a sexual relationship with an HIV-infected partner, A heterosexual man or woman in sexual relationship with high-risk partners, IVDA
- Tenofovir + emtricitabine
Toxoplasmosis: Pyrimethamine:
- Sulfadiazine
- Leucovorin
- Steroids for cerebral edema
- Treat for at least 6 wk
Cryptococcal meningitis:
- Amphotericin B
- Flucytosine
- Treat with above for 2 wk, then fluconazole for 8 wk
CMV retinitis: Ganciclovir
Esophageal cand idiasis:
- Fluconazole for 14-21 d
MAC: Clarithromycin:
- Ethambutol
- May add rifabutin if severe immunosuppression
PJP:
- Trimethoprim/sulfamethoxazole
- Pentamidine or dapsone for sulfa-allergic patients
- If PaO₂<70 mm Hg or A-a gradient >35 mm Hg, add prednisone 40 mg PO b.i.d for 5 d, then taper
Oral cand idiasis: Clotrimazole troches
HIV acute demyelinating polyneuropathy: Plasmapheresis

Medication

Common medication complications:
- Hypersensitivity reaction: Abacavir
- Pancreatitis:
  - Dideoxyinosine
  - Dideoxycytidine
  - Didanosine
  - Lamivudine
  - Cotrimoxazole
  - Pentamidine
  - Ritonavir
  - Stavudine
  - Zalcitabine
- Peripheral neuropathy:
  - Didanosine
  - Isoniazid
  - Linezolid
  - Stavudine
  - Zalcitabine
- Kidney stones: Indinavir and atazanavir
- Hepatotoxicity: All agents to some degree:
  - Nevirapine
  - Didanosine
  - Stavudine
- Lactic acidosis: Stavudine:
  - Didanosine
- Stevens-Johnson syndrome:
  - Nevirapine
  - Atazanavir
  - Delavirdine
  - Efavirenz
  - Cotrimoxazole
  - Trimethoprim/sulfamethoxazole
- Hemolytic anemia:
  - Dapsone (used for treatment of TB)
  - Zidovudine with ribavirin
- Psychosis: Efavirenz
- Hypoglycemia: Pentamidine
- Postural hypotension: Maraviroc
- Hyperlipidemia, truncal obesity, and atherosclerosis: Stavudine:
  - Protease inhibitors
- Dilated cardiomyopathy: Zidovudine
- Benign increase in unconjugated bilirubin: Atazanavir and indinavir
- Macrocytic anemia: Zidovudine
- Many cause some hematologic effects, GI upset, and rash

Follow-Up ⬆ ⬇

Disposition

Admission Criteria

Unexplained fever with CNS involvement or suspected endocarditis
Neutropenic fever
Hypoxemia (PaO₂<70 mm Hg)
Cardiac symptoms suggestive of ACS
Pericardial effusion
Suspected bacterial pneumonia or TB
A change in neurologic status
New-onset seizures
Hemodynamic instability
Inability to ambulate or tolerate oral intake
Intractable diarrhea with dehydration

Discharge Criteria

The patient can maintain adequate oral intake, provide self-care, and ambulate

Issues for Referral

Patient should be referred to a primary HIV care provider for initiation of ARV therapy regimen and ongoing care
Be alert for signs of depression and refer for counseling or psychiatric treatment as this may inhibit treatment compliance
HIV patients are at higher risk for many malignancies - refer those with concerning symptoms for follow-up

Pearls and Pitfalls ⬆ ⬇

Immune reconstitution inflammatory syndrome usually manifests within 8 wk of initiation of HAART as symptoms of opportunistic or autoimmune disease
For occupation exposures, there is a low risk of seroconversion (0.3% for significant percutaneous exposure and 0.09% for mucocutaneous)
HIV patients on HAART should be considered at higher risk for insulin resistance and acute coronary syndrome/CAD, independent of other risk factors
Measure oxygen saturation after walking in patients with a normal CXR and symptoms of pneumonia to help diagnose PCP
HIV is an independent risk factor for COPD, pulmonary hypertension, CVA, venous thromboembolic disease, TTP, osteoporosis, and osteonecrosis of the hip

Additional Reading ⬆ ⬇

DinennoEA, PrejeanJ, IrwinK, et al. Recommendations for HIV screening of gay, bisexual, and other men who have sex with men—United States, 2017 . MMWR Morb Mortal Wkly Rep. 2017;66(31):830-832.
HurtCB, NelsonJAE, Hightow-WeidmanLB, et al. Selecting an HIV test . Sex Transm Dis. 2017;44(12):739-746.
StanleyK, LoraM, MerjavyS, et al. HIV prevention and treatment: The evolving role of the emergency department . Ann Emerg Med. 2017;70(4):562-572.

Codes ⬆

ICD9

042 Human immunodeficiency virus [HIV] disease
V08 Asymptomatic human immunodeficiency virus [HIV] infection status
007.4 Cryptosporidiosis
176.9Kaposi's sarcoma, unspecified site
007.8 Other specified protozoal intestinal diseases
112.84 Cand idal esophagitis
136.3Pneumocystosis

ICD10

A07.2 Cryptosporidiosis
B20 Human immunodeficiency virus [HIV] disease
Z21 Asymptomatic human immunodeficiency virus infection status
C46.9 Kaposi's sarcoma, unspecified
A07.3 Isosporiasis
B37.81 Cand idal esophagitis
B59 Pneumocystosis

SNOMED

86406008 human immunodeficiency virus infection (disorder)
62479008acquired immune deficiency syndrome (AIDS) (disorder)
58777003 Infection by Cryptosporidium (disorder)
109385007 Kaposi's sarcoma (disorder)
20639004 Cand idiasis of the esophagus (disorder)
415125002 Pneumocystosis jiroveci pneumonia (disorder)
421510000 Isosporiasis associated with AIDS (disorder)

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Basics ⬇

Diagnosis ⬆ ⬇