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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, serum Toxoplasma IgG/IgM and (ideally) CSF Toxoplasma PCR (though CSF Toxoplasma PCR has a low sensitivity). Response to empiric therapy (~90% will have radiographic improvement after 14 days) can also be diagnostic. Brain biopsy may be indicated if diagnostic uncertainty.
  • Management: Pyrimethamine, sulfadiazine, and leucovorin is the preferred regimen, discuss dosing with pharmacy. Alternative regimens: clindamycin + pyrimethamine + leucovorin, Bactrim, atovaquone + pyrimethamine + leucovorin

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.
  • Management: Initiation of ART (there is no specific JC virus-directed therapy), IRIS may occur in which case clinical worsening before improvement may be seen. Fatal if HIV goes untreated.
  • 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, CSF culture. 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 culture is negative (note: Cryptococcus grows well on standard bacterial culture media). Following sterilization of CSF, consolidation therapy consists of high dose fluconazole for at least 8 weeks, followed by maintenance therapy with fluconazole for one year. Pts may require serial LP or VP shunt 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! May cause complete retinal detachment. Check serum CMV PCR (or vitreous if able)
  • Management: IV ganciclovir or PO valganciclovir (+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.
    • Transbronchial biopsy, BAL, or induced sputum with cytology and GMS stain.
    • Sputum Pneumocystis PCR can be done, but this is a send-out with long turn-around-time
    • Consider 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. Check ABG on ROOM AIR to consider of adding adjunctive steroids (If A-a gradient >/=35 mmHg and/or PaO2 <70 mmHg). 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 pt 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 smears/cultures collected at least 8 hours apart (or 2 smears/cultures with 1 GeneXpert) . 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.


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

  • DLBCL, Burkitt’s, immunoblastic (subset of DLBCL), primary effusion lymphoma, 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 (e.g.: 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 pts, 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 pts 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, Cryptococcosis, and Coccidioidomycosis

  • 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

Multicentric Castleman’s Disease

  • See “Plasma Cell Dyscrasias” section in Hematology/Oncology for more details