AIDS Defining Conditions

AIDS Defining Clinical Conditions – Rebecca Choudhury

AIDS is defined by HIV infection with concurrent absolute CD4 count <200, CD4 percentage <14%, or one of the following conditions, predominately opportunistic infections and HIV associated malignancies





CNS toxoplasmosis

  • Presentation: Variable, depending on disease burden/location, may include AMS, headache, seizure, ataxia, and focal neurologic deficits, +/- fever and flu-like symptoms
  • Evaluation: MRI w/Ring-enhancing lesions on brain imaging (Note: can appear similar to CNS lymphoma), serum Toxoplasma IgG/IgM and (ideally) CSF Toxoplasma PCR. Brain biopsy may be indicated if diagnostic uncertainty.
  • Management: Pyrimethamine, sulfadiazine, and leucovorin is the preferred regimen, discuss dosing with pharmacy. Alternative regimens: clindamycin, Bactrim, atovaquone, and/or azithromycin.



Progressive multifocal leukoencephalopathy (PML)

  • Presentation: chronic (weeks to months), progressive neurologic dysfunction, particularly incoordination and other motor dysfunction, aphasia, sometimes cognitive impairment and personality changes
  • Evaluation:  MRI brain w/patchy areas of demyelination in the subcortical white matter; location is variable, but parietal, occipital, and cerebellar involvement are common. JC virus PCR from CSF. Brain biopsy (uncommonly done)
  • Management: Initiation of ART may slow/stop progression. Fatal if HIV goes untreated.



HIV-related encephalopathy

  • Presentation: Similar to other progressive dementias, with short term memory loss followed by worsening global cognitive dysfunction, motor deficits, sometimes seizures in late stages
  •  Evaluation: MRI w/diffuse cerebral atrophy and/or demyelinating lesions similar to PML. CSF w/elevated protein +/- lymphocytic pleocytosis, with no alternative cause. Send HIV RNA from the CSF, usually + in HIV encephalopathy



Cryptococcal meningitis

  • Presentation: Subacute to chronically worsening HA and fevers; meningismus and photophobia may be present but are often absent; rarely, focal neurologic deficits
  • Evaluation: LP to check opening pressure and can send serum and CSF Cryptococcus Ag. Brain imaging may be non-diagnostic
  • Treatment: Induction therapy with amphotericin and flucytosine x14 days (at least), with repeat LP close to end of induction to confirm CSF inflammation is improving and fungal culture is negative. Maintenance therapy consists of high dose fluconazole for at least 8 weeks. Pts may require serial LP to manage ICP
  • Delay ART for several weeks after start of treatment to avoid risk of IRIS.



CMV retinitis (with vision loss)

  • Presentation: Blurry vision, focal blind spots, visual field deficits, or scotomas and floaters. Typically begins unilateral, though often progresses to bilateral involvement.
  • Evaluation: Always consult ophtho if you suspect it! Hemorrhagic retinitis, “tomato soup and milk” appearance on dilated exam. May cause complete retinal detachment. Check CMV pcr serum (or vitreous)
  • Management:  PO valgancyclovir (+intravitreous ganciclovir or foscarnet in severe disease). If not on ART, must delay ART for at least 2 weeks after start of CMV retinitis treatment to prevent immune recovery uveitis





 Pneumocystis jirovecii pneumonia (PJP)

  • Presentation: fever, shortness of breath, cough (usually non-productive), sometimes night sweats and weight loss. Hypoxia out of proportion to exam.
  • Evaluation: CT chest appearance usually bilateral and diffuse with GGOs and cystic lesions of varying size. Large cysts can rupture, causing pneumothorax.
    • Induced sputum (or bronchoscopy sample) with cytology and GMS stain.
    • Send serum LDH and 1,3-BD-glucan:  should be elevated, but are nonspecific.
  • Management: Bactrim is the preferred treatment; PO is preferable as Bactrim is 100% bioavailable. **If patient is hypoxic, need to consider of adding steroids, can measure A-a gradient. Alternative regimens may include primaquine + clindamycin or IV (NOT inhaled) pentamidine.



Pulmonary tuberculosis

  • Presentation: With low CD4, can have upper lobe cavities but also atypical radiographic pattern, including a normal-appearing CXR. Have a high degree of suspicion in any patient with advanced HIV and respiratory complaints.
  • Evaluation: TB skin tests and IGRAs have a high false negative rate in advanced HIV. At VUMC, any pt with HIV and respiratory complaints must be placed on airborne until TB ruleout- 3 sputum mycobacterial cultures collected at least 8 hours apart. If concentrated smear is negative x3, TB is unlikely (though have to follow up final culture to be sure).
  • Management: RIPE therapy is the standard initial treatment, with adjustment if needed for drug resistance or contraindications



Herpes simplex tracheobronchitis and/or pneumonitis/pneumonia

  • Evaluation: bronchoscopy with positive HSV PCR from BAL +/- lung biopsy. (Usually associated with HSV-1)
  • Management:  agent and duration not well defined for bronchopulmonary disease; depending on severity of presentation, likely IV acyclovir to start followed by transition to PO antiviral once evidence of clinical improvement, for a total of 10-14 days.



Recurrent pneumonia NOS

Histoplasmosis, cryptococcosis, coccidiomycosis, and non-TB mycobacterial infections (including MAC) limited to the pulmonary system are not AIDs defining illnesses, though pts with advanced HIV and other severely immunosuppressed states are at higher risk.





Esophageal candidiasis

  • Presentation: Dysphagia, odynophagia or both. Concurrent oropharyngeal candidiasis (“thrush’) is common but not universal.
  • Evaluation: Typically presumptive. Treatment is the test; start fluconazole and consider EGD if symptoms do not improve after several days (in which case candidiasis may be severe, or it might not be the cause)
  • Management: Fluconazole; nystatin is ineffective, especially in the severely immunocompromised



Herpes simplex esophagitis

  • Evaluation: EGD shows diffuse ulcerations throughout the esophagus; in severe disease ulcers may coalesce into dark patches, “black esophagus.” Esophageal biopsy is definitive, but can infer based on EGD appearance and serum studies.
  • Management: Similar to other mucocutaneous infections, consider IV acyclovir at first and transition to PO once clinically improved



CMV esophagitis/enteritis/colitis

  • Presentation: GI bleeding (colitis) or dysphagia and odynophagia (esophagitis)
  • Evaluation: serum CMV PCR, consult GI for consideration of EGD/colonoscopy
  • Management: (val)ganciclovir, foscarnet if ganciclovir resistance or contraindication



Chronic (>1 mo) intestinal isosporiasis

  • Evaluation: Stool ova/parasite can capture Iospora belli (new name Cystoisospora belli), may need serial analysis due to intermittent shedding. Oocysts may also be seen on duodenal biopsy.
  • Management: Bactrim; pyrimethamine + leucovorin if Bactrim is contraindicated


Chronic intestinal cryptosporidiosis

  • Presentation: Diarrhea; may infect respiratory tract, causing nonproductive cough
  • Evaluation: on GiPP or Cryptosporidium Ag
  • Management: Early initiation or optimization of ART; Monotherapy with nitazoxanide is preferred; raising CD4 count >100 is necessary to cure infection



Recurrent salmonella septicemia

  • Generally sensitive to fluoroquinolones, but if not clinically improving as expected you can request sensitivities from the microbiology lab.





Non-Hodgkin’s lymphoma - Burkitt’s, immunoblastic (subset of DLBCL), and 1º CNS



Kaposi’s sarcoma

  • Presentation: Distinctive mucocutaneous lesions, usually raised, papular, violaceous or darkly colored, non-tender and non-pruritic. Can also involve the visceral organs (esp lungs and GI tract) and deep lymphatic system.
  • Evaluation: clinical, tissue biopsy for staging, HHV-8 serum PCR.
  • Management: Limited mucocutaneous disease may resolve with initiation/optimization of ART, but widespread or resistant disease may require additional local therapies (ex radiation) or systemic chemo
  • Bacillary angiomatosis (caused by Bartonella) may present similarly, but can be distinguished from KS on biopsy. It is neither a cancer nor an AIDS defining clinical condition, and is usually treated with doxycycline.



Cervical cancer

  • Presentation, diagnosis, and treatment are essentially the same as in HIV-negative patients, but incidence is higher and disease progression is often more rapid





Extrapulmonary or disseminated Mycobacterial infection (TB and non-TB)

  • TB can go everywhere; some notable extrapulmonary sites include lymph nodes (e.g., scrofula), bones and joints (e.g., Pott’s disease of the spine), pleura and pericardium, GU tract, and CNS. Dx can come from tissue culture and sometimes MTB PCR for more rapid detection (needs ID approval).
  • TB-IRIS may be severe (esp with high infection burden) and hard to distinguish from TB treatment failure; can also be seen in adequately treated TB (provoked by the presence of dead bacteria) and undiagnosed latent TB.
  • Disseminated MAC is usually diagnosed with AFB blood culture (only 1 positive needed). Think about it in patients with uncontrolled HIV and severe immunosuppression (esp CD4 <50), with unintentional weight loss, chronic diarrhea and/or dyspnea, and evidence of GI malabsorption or with bone marrow suppression



Extrapulmonary or disseminated Histoplasmosis, Cryptococcocosis, and Coccidiodomycosis

  • Can be difficult to distinguish based on clinical presentation and imaging alone. Diagnosed by culture and/or antigen testing depending on the organism and site of infection, and diagnosis may be supported by serologic studies.
  • Initial treatment of choice: liposomal amphotericin B in almost all cases



 Chronic mucocutaneous HSV

  • Defined as mucocutaneous lesions present for >1 month, can be present at any site