Initial risk assessment

Assess for severity of illness (hemodynamic instability, sepsis, altered mentation). History: Symptoms, ART and prophylaxis adherence, prior OIs, travel, sexual history, possible exposures
Exam: Pulmonary, abdominal, eye, skin/mucosa, anogenital, lymph node, neuro exams
Labs: CBC with diff, complete metabolic panel, urinalysis, CD4 count and HIV viral load (if not recently obtained)

Ocular symptoms

DDx: CMV, VZV, HSV, Bartonella, syphilis, TB, Toxoplasma, bacterial or fungal keratitis, microsporidiosis, HIV retinopathy

Work-up: Urgent ophthalmologic eval for all acute vision loss or eye pain
Herpesvirus serologies +/– PCR, RPR with treponemal Ab, toxo IgG, corneal biopsy or vitreal tap for path and Cx

Respiratory symptoms

CD4 >250 DDx: TB, bacterial pneumonia, Coccidioides, respiratory viruses, lymphoma, pulmonary edema, noninfectious causes (e.g., PE)

CD4 <250 DDx: PCP, endemic fungi (Histoplasma, Cryptococcus, Coccidioides), mycobacterial, lymphoma, KS

Work-up in low CD4: Imaging (CXR +/– CT scan); bacterial, fungal and AFB blood and sputum Cx, TB PCR sputum, PCP DFA x3, LDH, ABG, serum cryptococcal Ag, urine Histoplasma Ag, respiratory viral panel

Consider early bronchoscopy if initial work-up (–) or clinical worsening.

Neurologic symptoms

Meningoencephalitis: Bacterial meningitis, neurosyphilis, TB, Cryptococcus, other endemic fungi, HSV, VZV, CMV, PML (JC virus), HIV encephalopathy

CNS mass lesion: Toxoplasma, PCNSL (EBV-associated), TB, endemic fungi, Nocardia, brain abscess, syphilitic gumma, CNS Chagas disease, primary brain tumor

Work-up: Contrasted neuroimaging (CT scan or MRI), LP (opening pressure, cell count, diff, glucose, protein, Gm stain/Cx)

Based on initial studies, can obtain additional serum (e.g., toxo IgG, RPR, crypto Ag) or CSF studies (e.g., fungal Cx and serologies, crypto Ag, AFB Cx, TB PCR, VDRL, viral PCR)

Undifferentiated fever (FUO)/multiorgan disease

DDx: Bacterial sepsis, TB, MAC, Brucella, Bartonella, endemic fungi, CMV, EBV, HHV-8 (multicentric Castleman’s), parvovirus B19, malaria, visceral leishmaniasis, lymphoma, disseminated KS, HLH

Work-up: Bacterial, AFB and fungal blood Cx; fungal serologies, crypto Ag, urine histo Ag, CMV PCR, HHV-8 PCR, LDH, ferritin, blood smear consider CT scan of chest, abdomen/pelvis consider biopsy of bone marrow, lymph node or liver for path and Cx

Hepatobiliary symptoms

DDx: Viral hepatitis (A, B, C, E), lymphoma or HCC, MAC, TB, syphilis, Bartonella, Histoplasma, CMV, cryptosporidiosis, microsporidiosis, AIDS cholangiopathy, DILI

Work-up: Pattern of LFT instructive; viral hepatitis Ab, routine and AFB blood Cx, CMV PCR, fungal Ab, RPR; hepatic imaging (US +/– CT) followed by ERCP or liver biopsy if indicated

Gastrointestinal symptoms

Upper GI (dysphagia, pain): Candidiasis, CMV, HSV, aphthous ulcers, KS, lymphoma or carcinoma

Lower GI (diarrhea): Bacterial enterics, C. difficile, Giardia, cryptosporidiosis, Cyclospora, microsporidiosis, Cystoisospora, CMV, MAC, KS, lymphoma

Work-up
Upper GI: Empiric Candida Rx if thrush present; endoscopy for biopsy with stains, Cx and PCR
Lower GI: Stool for routine Cx, C. diff, Giardia/Cryptosporidia Ag, O&P, modified AFB, trichrome stains; AFB blood and stool Cx, blood CMV PCR

Consider endoscopy with biopsy if initial work-up (–) or high concern for CMV colitis

End