• Clinical science

HIV-associated conditions

Abstract

AIDS (acquired immunodeficiency syndrome) is the final stage of HIV infection and is defined by the development of certain diseases (AIDS-defining conditions) or a CD4 cell count of < 200 cells/μL in HIV-infected patients. AIDS-defining conditions include malignancies (e.g., primary lymphoma of the brain) and certain opportunistic infections (e.g., Pneumocystis pneumonia, cerebral toxoplasmosis). There are also opportunistic infections that commonly occur in HIV patients that are not considered AIDS-defining conditions. This learning card provides an overview of AIDS-defining and other HIV-associated conditions.

Overview of HIV-associated conditions

AIDS-defining conditions

The CDC defines AIDS as the development of an AIDS-defining condition or a CD4 cell count of < 200 cells/μL in HIV-infected patients.

AIDS-defining condition CD4 count (in cells/μL) Features Management

HIV wasting syndrome

  • Variable
  • Unintentional weight loss of ≥ 10%, fatigue, fever, diarrhea
  • Caused by various factors (e.g., diarrhea due to secondary infection, reduced appetite, changes in metabolism)
  • Optimization of nutrition
  • Prevention of nausea/vomiting
  • Treatment of gastrointestinal infections (e.g., CMV colitis)
Kaposi sarcoma
  • Variable (typically < 500/mm3)
  • Vascular proliferation on skin and mucosae (initially particularly face/oral cavity and chest)
  • Caused by HHV-8
  • Skin biopsy: spindle-shaped cells, leukocyte infiltration, and angiogenesis
  • Local: surgical excision, laser therapy or cryotherapy
  • Systemic: α-interferon
Cervical cancer (invasive)
  • Variable
Lymphoma

Recurrent or multiple bacterial infections (generally)

  • Variable
Mycobacterial infections (other)
  • Variable
Lymphoid interstitial pneumonia or pulmonary lymphoid hyperplasia complex
  • Variable
  • Lung biopsy: inflammatory alveolar infiltrates (including polyclonal B-cells)
  • Symptomatic
Reactivation tuberculosis
  • < 400
Coccidioidomycosis
  • < 250
Cryptosporidiosis
  • < 200
  • Chronic, watery diarrhea with nausea and abdominal pains
  • Acid-fast cysts in stool
  • Antiparasitic therapy (e.g., nitazoxanide)
HIV-related encephalopathy (AIDS dementia)
  • < 200 (typically untreated patients with advanced HIV infection)
  • Subcortical dementia
  • See “HIV-associated CNS lesions” below for details.
  • Optimize antiretroviral treatment, but avoid efavirenz
Progressive multifocal leukoencephalopathy (PML)
  • < 200
  • Focal-neurologic deficits, altered mental status, impaired vigilance
  • MRI: disseminated, non-enhancing white matter lesions without mass effect
  • Supportive
Pneumocystis pneumonia
  • < 200
  • Most common cause of death in patients with AIDS!
  • Gradual onset with low-grade fever, dyspnea and non-productive cough
  • Laboratory: ↑ beta-D-glucan
  • CXR: diffuse bilateral infiltrates (“ground-glass appearance)
Isosporiasis
  • < 200
Histoplasmosis
  • < 150
Cerebral toxoplasmosis
  • < 100
  • Impaired vigilance, focal neurologic deficits, seizures, fever
  • Contrast CT/MRI: multiple contrast-enhanced lesions
  • Most common cause of cerebral abscess in HIV patients
  • Toxoplasma chorioretinitis is also possible.
Cryptococcosis (extrapulmonary, especially cryptococcal meningitis)
  • < 100

Candidiasis

  • < 100
Herpes simplex infections
  • < 100
  • Unusual manifestations of infection, including:
    • Chronic ulcers (> 1 month)
    • Esophagitis (onset at age > 1 month)
    • Bronchitis or pneumonitis
  • See herpes virus infections.
Cytomegalovirus infection
  • < 50
  • CMV colitis endoscopy shows linear ulcers
  • CMV retinitis: fundoscopy shows cotton-wool spots
  • Biopsy: intracellular inclusions (“owl's eye”)
Tuberculosis-like disease
  • < 50
  • Caused by Mycobacterium avium complex (MAC) infection
  • Cough, sputum, weight loss, night sweats, fever

Other HIV-associated conditions

Adequate HIV treatment (cART) is key to minimizing the risk of opportunistic infections!

Some AIDS-defining conditions are opportunistic infections, but the terms are not interchangeable!

References:[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]

Mycobacterium avium complex (MAC) infection

References:[1][2][3][16][23]

Progressive multifocal leukoencephalopathy (PML)

References:[2][24]

Kaposi sarcoma

  • Definition: malignant, multifocal, highly vascularized tumor caused by the human herpesvirus 8 (HHV8 )
  • Classification:
  • Clinical features
    • Multiple cutaneous or visceral, elevated tumors with rapid growth
    • Initial manifestation on skin and mucosae (especially face/oral cavity and chest)
    • Over time, organ involvement is possible.
  • Diagnostics
    • Skin biopsy: spindle-shaped cells, leukocyte infiltration, and angiogenesis.
    • Chest x-ray, sonography of the abdomen and lymph nodes
  • Treatment
    • Treatment of the underlying disease → antiretroviral treatment in HIV patients
    • Symptomatic therapy:
      • Local: surgical excision, laser therapy, or cryotherapy
      • Systemic: α-interferon
  • Prognosis: very variable

References:[1][25]

Bacillary angiomatosis

References:[26]

HIV-associated ocular manifestations

Features CD4 count
HIV retinopathy
  • Caused by a microvascular disorder
  • Fundoscopic findings
    • Small cotton wool spots
    • Microaneurysms
    • Retinal hemorrhages
  • Tend to self-resolve without progression
  • Not painful
  • Vision usually unaffected
  • Variable
Herpes simplex keratitis
  • History of HSV infection is common
  • Slit-lamp examination: dendritic corneal lesions
  • Fundoscopic findings are normal
  • Painful and watery eye(s)
  • Blurry vision
  • Variable
Varicella zoster retinitis
  • Rare
  • Fundoscopic findings: retinal necrosis (starting from the periphery)
  • Painful
  • Severe loss of vision
  • Variable
Cytomegalovirus retinitis
  • Fundoscopy findings
    • Hemorrhages (red spots)
    • Perivascular white opacities resembling cotton-wool spots (larger than HIV retinopathy!)
    • “Pizza pie” appearance: combination of red spots on white opacities
    • Retinal detachment
  • Not painful
  • Vision initially unaffected
  • Vision loss occurs if the retina detaches or the posterior pole (optic nerve or macula) is affected.
  • < 100/μL
Toxoplasma retinitis
  • Fundoscopic findings: raised yellow-white cottony lesions (distribution of the lesions not related to vessels)
  • Painful
  • Visual impairment
  • < 100/μL

HIV-associated CNS lesions

Differential diagnosis of CNS lesions in HIV-positive patients with CD4+ T-cell count < 200/mm3:

Conditions Description Clinical features Neuroimaging Further tests Treatment
Cerebral toxoplasmosis
  • Contrast CT: multiple ring-enhancing lesions predominantly in the basal ganglia
  • CSF: pleocytosis, elevated protein
  • Pyrimethamine, sulfadiazine, and leucovorin
Primary CNS lymphoma (PCNSL)
  • An extranodal non-hodgkin lymphoma
  • Associated with EBV infection
  • Headache
  • Focal neurologic deficits
  • Neuropsychiatric symptoms (e.g., personality changes)
  • Seizures (< 15%)
  • Contrast CT: solitary ring-enhancing lesion
  • High dose methotrexate with/without whole brain radiotherapy
  • Oral/IV corticosteroids: after histological diagnosis; to control symptoms of raised ICP
  • Surgical resection: for a solitary PCNSL located in a non-eloquent region of the brain
Cerebral abscess
  • Disseminated infection
  • Fever
  • Headache
  • Symptoms of elevated intracranial pressure
  • Neurologic deficits
  • Seizures
  • Contrast CT: focal intraparenchymal lesion with a central hypodense (necrotic) area and peripheral ring enhancement
Progressive multifocal leukoencephalopathy (PML)
  • Demyelinating disease of the CNS caused by reactivation of the JC virus
  • Rapidly progressive focal-neurologic deficits (e.g., visual field defects, hemiparesis)
  • Cognitive impairment
  • Impaired vigilance
  • Contrast CT: disseminated, non-enhancing white matter lesions without mass effect
  • Supportive therapy
HIV-associated encephalopathy (AIDS dementia)
  • Dissemination of HIV into the CNS (particularly in advanced HIV infection and/or untreated patients)
  • Subcortical dementia (memory loss, depression, movement disorders)
  • Progression to severe neurologic deficits (impaired vigilance, aphasia, gait disturbances)
  • MRI: multiple subcortical hyperintense non-enhancing lesions

References:[27][28][10][29][30][31][32][33]