Overview
The tables below summarize the defining conditions of acquired immunodeficiency syndrome (AIDS).
| AIDS-defining condition | CD4 count (cells/µL) | Clinical presentation | Management (in addition to HIV treatment) |
|---|---|---|---|
| Mycobacterium avium complex | < 50 |
| Treatment: macrolide and ethambutol |
| Mycobacterium tuberculosis | < 200 |
|
|
| Salmonella septicemia | < 200 |
| IV fluoroquinolones or 3rd-generation cephalosporins |
| AIDS-defining condition | CD4 count (cells/µL) | Clinical presentation | Management (in addition to HIV treatment) |
|---|---|---|---|
| Cytomegalovirus (CMV) | < 50 |
| Ganciclovir, valganciclovir, foscarnet, or cidofovir |
| Herpes simplex virus | < 100 | Non-healing lesions, tracheitis, pneumonitis, esophagitis, keratitis, meningoencephalitis | Acyclovir, valacyclovir, or famciclovir |
| JC virus (progressive multifocal leukoencephalopathy) | < 200 | Focal-neurologic deficits, cognitive impairment | Supportive |
| AIDS-defining condition | CD4 count (cells/µL) | Clinical presentation | Management (in addition to HIV treatment) |
|---|---|---|---|
| Esophageal candidiasis | < 100 | Odynophagia, oral thrush may be present | Fluconazole |
| Pneumocystis jirovecii pneumonia | < 200 | Fever, dyspnea, non-productive cough | Treatment and prophylaxis: TMP-SMX |
| Cryptococcal meningitis | < 100 | Fever, headache, neck stiffness, AMS, neurologic deficits | Amphotericin B and flucytosine, followed by fluconazole |
| CNS toxoplasmosis | < 100 | Headache, fever, AMS, focal neurologic deficits, seizures |
|
| Coccidioidomycosis (disseminated, extrapulmonary) | < 250 | Fever, night sweats, dyspnea, cough, lymphadenopathy, weight loss |
|
| Histoplasmosis (disseminated, extrapulmonary) | < 150 | Fever, night sweats, fatigue, weight loss, nausea and vomiting, dyspnea, cough, skin lesions | Amphotericin B or itraconazole |
| Cryptosporidiosis | < 100 | Diarrhea, AIDS cholangiopathy | Nitazoxanide or paromomycin |
| Cystoisosporiasis | < 50 | Watery, non-bloody diarrhea, anorexia, abdominal pain, vomiting | TMP-SMX |
TMP-SMX: trimethoprim-sulfamethoxazole
CNS: central nervous system
| AIDS-defining condition | CD4 count (cells/μl) | Clinical presentation | Management (in addition to HIV treatment) |
|---|---|---|---|
| Lymphoma (Burkitt’s, DLBCL) | Burkitt’s: < 50; DLBCL: Variable | Constitutional symptoms, extranodal mass with rapid growth | Depends on the stage and includes chemotherapy, immunotherapy, and radiation therapy |
| CNS lymphoma | < 50 | Headache, AMS, focal neurological deficits, seizures, constitutional symptoms | Chemotherapy |
| Invasive cervical carcinoma | Variable | Watery, bloody vaginal discharge, pelvic pain |
|
| Kaposi’s sarcoma | < 500 | Malignant vascular lesions of the skin, mucosa, GI, and respiratory tract |
|
DLBCL: diffuse large B cell lymphoma
CNS: central nervous system
HPV: human papillomavirus
GI: gastrointestinal
| AIDS-defining condition | CD4 count (cells/μl) | Clinical presentation | Management (in addition to HIV treatment) |
|---|---|---|---|
| Wasting syndrome | Variable | Weight loss of ≥ 10%, fatigue, fever, diarrhea | Nutritional care, treatment of secondary infections |
| HIV-associated dementia | < 200 | Cognitive dysfunction, behavioral and mood changes, motor symptoms | Optimize antiretroviral treatment. |
| HIV + | ≤ 200 | CD4 ≤ 200 is defined as AIDS per CDC | ART |
Wasting Syndrome
Definition
- An unintentional weight loss of ≥ 10% in the presence of ≥ 1 of the following:
- Chronic diarrhea for ≥ 30 days
- Chronic weakness
- Documented fever for ≥ 30 days
- Not attributable to a concurrent condition other than HIV infection
Possible etiologies and pathophysiology
- Inadequate caloric intake
- GI malabsorption
- Possibly due to AIDS enteropathy
- Associated with:
- Motility disturbances
- Mucosal atrophy
- ↑ Metabolic rate → diversion of energy expenditures to immune function
- Disruption in hormone function
- ↓ Testosterone → ↓ muscle mass
- ↓ Insulin-like growth factor production
Clinical presentation
- Weight loss characterized by depletion of fat and lean tissue
- Associated symptoms:
- Fever (intermittent or constant)
- Diarrhea (≥ 2 stools/day)
A patient with wasting syndrome due to AIDS
Image: “HIV Wasting Syndrome” by Department of Medicine, Ahmadu Bello University Teaching Hospital (ABUTH), Zaria, Nigeria. License: CC BY 3.0Management
- Antiretroviral therapy
- Treatment of secondary infections
- Optimize nutrition:
- Dietary counseling
- Multivitamin and mineral supplementation
- Medical therapy is reserved for those who fail the above measures.
- Appetite stimulants
- Growth hormone
- Androgenic steroids
AIDS Cholangiopathy
Overview
- Biliary obstruction due to strictures from opportunistic infections
- CD4 count < 200 cells/μL (usually < 100 cells/μL)
- Mean survival after diagnosis is 7–12 months.
- Common pathogens:
- Cryptosporidium parvum (20%–57% of cases)
- Cytomegalovirus (10%–20% of cases)
- Herpes simplex virus
- Microsporidium
- Giardia
- Mycobacterium avium complex (MAC)
- Pathophysiology:
- Opportunistic infections of the biliary system → chronic biliary inflammation → scarring, strictures, and stenosis
- Biliary obstruction → cholestatic liver damage
Clinical presentation
- Right upper and epigastric abdominal pain
- Nausea and vomiting
- Fever
- Jaundice
- Diarrhea (due to Cryptosporidium)
Diagnosis
- Liver function tests
- Alkaline phosphatase ↑
- Aspartate transaminase (AST) and alanine aminotransferase (ALT) mild to moderately ↑
- Bilirubin is usually normal or mildly ↑
- Abdominal ultrasound
- Dilated intra- and extrahepatic bile ducts
- May appear normal
- Magnetic resonance cholangiopancreatography (MRCP): Assess for biliary strictures and stenosis.
- Endoscopic retrograde cholangiopancreatography (ERCP)
- Biopsies and biliary aspiration
- Determine etiology.
- Exclude cholangiocarcinoma.
- Allows for intervention on strictures or stenotic lesions
- Biopsies and biliary aspiration
Management
- ERCP
- Sphincterotomy
- Stenting
- Ursodeoxycholic acid
- For intrahepatic ductal disease
- Limited data
- Treat underlying infections (e.g., CMV, Cryptosporidium)
- Antiretroviral therapy
Chronic complications
- Acute cholangitis
- Liver failure
- Cholangiocarcinoma
Ocular Conditions
HIV retinopathy
- A disease of small blood vessels (microvasculopathy) of the eye
- 70% in advanced HIV
- Possible pathophysiology:
- Interruption of blood flow due to:
- Immune complex deposition
- ↑ Plasma viscosity
- HIV invasion of vascular endothelium
- Deposition of debris
- Interruption of blood flow due to:
- Clinical presentation: Most are asymptomatic.
- Fundoscopic findings:
- “Cotton-wool” spots
- Intraretinal hemorrhages
- Microaneurysms
- Telangiectasias
- No treatment is required.
Herpes simplex keratitis
- Corneal inflammation caused by herpes simplex virus (HSV) infection
- Types:
- Epithelial (dendritic) keratitis
- Disciform (localized endotheliitis) keratitis
- Stromal keratitis
- Clinical presentation:
- Tearing
- Foreign body sensation
- Vision loss
- Reversible in disciform keratitis
- Irreversible in stromal keratitis
- Photophobia
- Slit-lamp examination:
- Dendritic corneal lesions are diagnostic.
- Management:
- Topical therapy:
- Acyclovir, ganciclovir, or trifluridine
- Corticosteroids for stromal keratitis
- Systemic therapy: acyclovir or valacyclovir
- Topical therapy:
Slit lamp examination showing dendritic lesions in herpetic keratitis:
Seen here as irregular geographic patterns of ulceration highlighted in green after the application of yellow-orange fluorescein dye. The dye is taken up by damaged cornea (where the surface has been disrupted) so the area appears green under cobalt blue light.
Retinitis
CMV retinitis:
- CD4 count < 50 cells/μL
- Pathophysiology:
- Hematogenous spread of CMV to the eye
- Causes retinal necrosis and edema → atrophic scar tissue
- Tears in scar tissue → retinal detachment
- Clinical presentation:
- Painless central vision loss
- Scotomata (blind spots)
- Floaters
- Photopsia (flashing lights)
- Fundoscopic findings:
- Perivascular yellow-white retinal lesions
- Associated hemorrhage
- Management:
- Antiretroviral therapy
- Ganciclovir, valganciclovir, or foscarnet
Toxoplasma chorioretinitis:
- Ocular disease due to Toxoplasma gondii
- CD4 count < 100 cells/μL
- Pathophysiology:
- Focal necrotizing retinitis
- Granulomatous choroid inflammation
- Clinical presentation:
- Blurred vision
- Floaters
- Eye pain
- Fundoscopic findings:
- Raised, yellow-white cotton lesions
- Nonvascular distribution
- Management:
- Antiretroviral therapy
- Pyrimethamine + sulfadiazine + folinic acid (leucovorin)
Varicella zoster retinitis:
- Also known as progressive outer retinal necrosis
- CD4 < 100 cells/μL
- Pathophysiology:
- Rapidly progressing retinal necrosis
- Leads to retinal detachment
- Clinical presentation:
- Vision loss
- Rapid progression to blindness
- Some patients may have eye pain
- Fundoscopic findings:
- Patchy, peripheral retinal necrosis
- No involvement of retinal vasculature
- Management:
- Antiretroviral therapy
- Intravenous and intravitreal antiviral medications (ganciclovir, foscarnet, valganciclovir)
Fundoscopy of CMV retinitis
Image: “Fundus photograph-CMV retinitis” by National Eye Institute. License: Public Domain
Fundoscopy of toxoplasma chorioretinitis
Image: “Granular appearance of lesions” by Department of Ophthalmology and Visual Sciences, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, NY 10467, USA. License: CC BY 2.0
Note the yellow-white cotton lesions in both the right eye (A) and left eye (B).
Fundoscopy of progressive retinal outer necrosis, a rare disease caused by varicella zoster
Image: “Cracked mud appearance” by Medical Research Foundation, Chennai, India. License: CC BY 2.0
Central Nervous System Conditions
HIV-associated dementia
- Previously known as:
- AIDS dementia complex
- HIV encephalopathy
- HIV encephalitis
- CD4 count < 200 cells/μL
- Clinical presentation:
- Cognitive dysfunction
- Memory loss
- Poor attention and concentration
- Impaired executive functioning
- Behavioral and mood changes
- Apathy
- Decreased motivation
- Irritability
- Sleeplessness
- Restlessness and anxiety
- Psychosis, paranoia, and hallucinations
- Motor symptoms
- Slowed movement and gait
- Saccadic eye movements
- Dysdiadochokinesia
- Hyperreflexia
- Frontal release signs (grasp, root, glabellar reflexes)
- Cognitive dysfunction
- Diagnosis:
- Neuropsychological testing aids in the diagnosis.
- ≥ 2 standard deviations below the mean in ≥ 2 cognitive domains on neuropsychological testing
- Concomitant impairment in activities of daily living
- Cannot be explained by other conditions
- Magnetic resonance imaging (MRI)
- 1st-choice imaging modality
- Diffuse, patchy white matter hyperintensity
- Rule out other causes of encephalopathy.
- Lumbar puncture with cerebral spinal fluid (CSF) analysis
- Lymphocytic pleocytosis
- CSF HIV viral load is generally > plasma viral load
- Findings are nonspecific.
- Neuropsychological testing aids in the diagnosis.
- Management:
- Antiretroviral therapy
- Safety assessment
- Psychiatric evaluation
Magnetic resonance imaging in a patient with HIV-associated dementia
Axial T2 (a) and FLAIR (fluid-attenuated inversion recovery) (b) images showing bilateral symmetrical hyperintensity in the periventricular white matter
Central nervous system (CNS) toxoplasmosis
- Most common CNS infection in patients with AIDS
- CD4 count < 100 cells/μL
- Etiology:
- Reactivation of prior infection with T. gondii
- Transmitted through ingestion of oocysts after contact with infected cat feces
- Clinical presentation:
- Headache
- Fever
- Altered mental status
- Dull affect
- Stupor
- Coma
- Focal neurologic deficits
- Seizures
- Diagnosis:
- Computed tomography (CT) or MRI
- Single or multiple ring-enhancing lesions
- MRI is more sensitive.
- Lumbar puncture with CSF analysis
- Lymphocytic pleocytosis
- ↑ Protein
- Polymerase chain reaction (PCR) to identify T. gondii
- Computed tomography (CT) or MRI
- Management:
- Antiretroviral therapy
- Pyrimethamine + sulfadiazine + folinic acid (leucovorin)
- TMP-SMX is an alternative.
- Prophylaxis
- TMP-SMX
- Indicated in patients with a CD4 count < 100 cells/μL
Toxoplasmosis and AIDS
MRI showing ring enhancing of the capsule-thalamic lesion in a patient with hemichorea-hemiballismus
Primary CNS lymphoma
- Overview:
- Extra-nodal non-Hodgkin’s lymphoma
- Associated with Epstein-Barr virus (EBV) infection
- CD4 count < 50 cells/μL
- Clinical presentation:
- Headache
- Confusion and lethargy
- Focal neurologic deficits (hemiparesis)
- Seizures
- Constitutional (“B symptoms”)
- Fever
- Night sweats
- Weight loss
- Diagnosis:
- CT and MRI: usually a single ring-enhancing lesion
- Lumbar puncture and CSF analysis
- PCR for EBV DNA
- Cytology
- Brain biopsy
- Management:
- Chemotherapy (methotrexate)
- Antiretroviral therapy
Magnetic resonance imaging of a patient with primary CNS lymphoma
Image shows a single ring-enhancing mass in the left hemisphere.
Progressive multifocal leukoencephalopathy (PML)
- Overview:
- Demyelinating disease of the CNS
- Caused by reactivation of John Cunningham polyomavirus (JCV)
- Acquired during childhood
- Remains latent in organs (kidneys, lymphoid organs, CNS)
- CD4 count < 200 cells/μL
- Clinical presentation:
- Rapidly progressive symptoms
- Hemiparesis (most common)
- Aphasia and dysarthria
- Hemianopia
- Gait ataxia
- Cognitive impairment
- Impaired vigilance
- Headache
- Seizures (rare)
- Diagnosis:
- CT or MRI
- Disseminated, non-enhancing white matter lesions
- No mass effect
- Lumbar puncture with CSF analysis: PCR for JCV DNA
- Brain biopsy
- CT or MRI
- Management:
- Antiretroviral therapy
- Supportive care
Magnetic reonance imaging in a patient with PML
Axial FLAIR (left) and axial T2-weighted images (right) show extensive diffuse lesions in the subcortical and periventricular white matter.
Bacillary Angiomatosis
Overview
- CD4 count < 100 cells/μL
- Etiology:
- Causative organisms:
- Bartonella henselae (most common)
- B. quintana
- Transmission:
- Fleas and lice
- Cat scratches
- Causative organisms:
- Pathophysiology:
- Bartonella infection → vascular proliferation → angiomatous skin lesions
- Involvement of other organs:
- Respiratory tract
- Bone
- Lymph nodes
- GI tract
- Brain
Clinical presentation
- Cutaneous lesions
- Protuberant, red papules or nodules
- Friable (tend to bleed profusely with trauma)
- Subcutaneous nodules that may ulcerate
- Painful, osteolytic bone lesions
- Frequently of the long bones
- Associated with an overlying cellulitic plaque
- Smooth, purple, mucosal papules or plaques
Nodular lesions due to bacillary angiomatosis in a patient with AIDS
Image: “Bacillary angiomatosis” by Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru. License: CC BY 4.0, edited by Lecturio.Diagnosis
- Biopsy of affected tissue
- Vascular proliferation
- Protuberant, plump endothelial cells
- Scattered neutrophils and lymphocytes
- Dark-staining bacteria seen with Warthin-Starry silver staining
- Blood or tissue cultures
- PCR
Histopathology specimen from a patient with bacillary angiomatosis
A dark-staining cluster of B. quintana (indicated by an arrow) is revealed with Warthin-Starry staining of a tissue specimen.
Management
- Antibiotic therapy
- Erythromycin
- Doxycycline
- Monitor antibody titers
- Antiretroviral therapy
Kaposi’s Sarcoma
Overview
- Aggressive, malignant vascular tumors
- CD4 count < 500 cells/μL
- Etiology:
- Human herpesvirus type 8 (HHV-8)
- Commonly transmitted via saliva and sexual contact
Clinical presentation
- Cutaneous lesions
- Common sites:
- Lower extremities
- Face
- Oral mucosa
- Genitalia
- Appearance:
- Elliptical
- Assorted colors (pink, red, purple, brown)
- Papular or plaque-like
- Not painful or pruritic
- Yellow-green peri-lesional “halo”
- Associated lymphedema
- Common sites:
- Intraoral lesions
- Common sites:
- Hard palate
- Gingiva
- Trauma can lead to bleeding, ulceration, or secondary infection.
- Common sites:
- GI tract lesions
- Hemorrhagic or submucosal nodules
- Can occur anywhere along the GI tract
- Symptoms:
- Asymptomatic (most common)
- Weight loss and malabsorption
- Abdominal pain
- Nausea and vomiting
- Intestinal obstruction
- GI bleeding
- Pulmonary manifestations
- Cherry-red, elevated lesions
- Nodular, interstitial, or alveolar infiltrates
- Pleural effusion
- Symptoms:
- Dyspnea
- Fever
- Cough and hemoptysis
- Chest pain
Cutaneous lesions on the nose of a patient with Kaposi’s sarcoma
Image: “Kaposi’s sarcoma” by M. Sand et al. License: CC BY 2.0
Cutaneous lesions of Kaposi’s sarcoma
Image: “Kaposi’s sarcoma” by OpenStax College. License: CC BY 3.0Kaposi’s sarcoma presenting as violaceous papules in an HIV-positive patient’s mouth
Image: “Intraoral Kaposi’s sarcoma” by National Cancer Institute. License: Public Domain
Diagnosis
Biopsy confirms the diagnosis.
- Samples may be obtained from:
- Skin lesions
- Endoscopy (GI symptoms)
- Bronchoscopy (pulmonary involvement)
- Findings:
- Angiogenesis with aberrant proliferation of small vessels
- Vessels lack a basement membrane.
- Microhemorrhages
- Hemosiderin deposition
- Whorls of spindle-shaped cells
- Leukocyte infiltration
- Angiogenesis with aberrant proliferation of small vessels
Histologic findings of angiogenesis in Kaposi’s sarcoma
Image: “Kaposi’s Sarcoma” by National Cancer Institute. License: Public Domain
Biopsy showing new blood vessel formation (appear as open spaces) where there are dividing epithelial cells and some red blood cells
Biopsy image of Kaposi’s sarcoma
Image: “Kaposi’s sarcoma” by Lena Jakob et al. License: CC BY 4.0
Spindle cells are seen, and red blood cells are visualized within poorly defined slit-like vascular spaces.
Management
- Antiretroviral therapy can lead to a marked response.
- Local therapies to induce regression of tumors
- Intralesional chemotherapy (vinblastine)
- Radiation therapy
- Topical alitretinoin
- Systemic chemotherapy for advanced or rapidly progressing disease
Mycobacterium avium Complex Infection
Overview
- CD4 count < 50 cells/μL
- Causative organisms:
- M. avium
- M. intracellulare
- Transmission:
- Inhalation
- Ingestion of contaminated food or water
- Bacteria disseminate through the lymphatic system.
Clinical presentation
- Disseminated disease
- High fever
- Weight loss
- Night sweats
- Abdominal pain
- Diarrhea
- Focal lymphadenitis
- Commonly results from immune reconstitution inflammatory syndrome
- Occurs after initiation of antiretroviral therapy
- Paradoxical worsening of preexisting infectious conditions
- Fever
- Lymphadenopathy
- Commonly results from immune reconstitution inflammatory syndrome
- Other localized manifestations
- Mastitis
- Subcutaneous nodules
- Osteomyelitis
- Granulomatous hepatitis
- Paravertebral abscess
- Brain abscess
- Lung infiltrates
- Intestinal involvement
Diagnosis
- Blood cultures
- Tissue aspirate (lymph node)
- Associated laboratory abnormalities:
- Anemia
- Thrombocytopenia
- ↑ Alkaline phosphatase
- ↑ Lactate dehydrogenase
Management
- Macrolide plus ethambutol
- Rifabutin may be added for:
- Patients failing antiretroviral therapy
- Patients with a high bacterial burden
- Antiretroviral therapy
References
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