INFECTIOUS DISEASES
HIV/AIDS
Definition
• AIDS: HIV + CD4 <200/mm3 or AIDS-defining opportunistic infection (OI) or malignancy
Epidemiology
• ~1 million Americans living w/ HIV; ~34 million individuals worldwide
• 20% in U.S. are unaware of infection; 6th leading cause of death in 25–44-y age group
• Routes: sexual (risk is 0.3% for male-to-male, 0.2% for male-to-female, 0.1% for female-to-male transmission), IVDU, transfusions, needle sticks (0.3%), vertical (15–40% w/o ARV)
• Postexposure (risk infxn ~0.3%) Ppx: 2 NRTIs (+ PI or NNRTI if high-risk) × 4 wk
Acute retroviral syndrome (ARS)
• Occurs in ~40–90% of Pts ~2–6 wk after infxn; ± ELISA, 
viral load (2 wk after infxn); early ART in ARS may be beneficial (NEJM 2013;368:207 & 218)
• Mono-like syndrome (↑ mucocut. & neuro manifestations compared to EBV or CMV)
Diagnostic studies
• ELISA for HIV-1 Ab/Ag: 1–12 wk after acute infxn; >99% Se; 1° screening test
• Western blot: if ≥2 bands from HIV genome; >99% Sp; confirmatory after ELISA
• Rapid preliminary tests: 4 Ab tests; use saliva, plasma, blood or serum; 99% Se & 96–99% Sp (Annals 2008;149:153); PPV in low prev populations as low as 50%
• PCR (viral load): detects HIV-1 RNA in plasma; assay range is 48–10 million copies/mL ~2% false , but usually low # copies; in contrast, should be very high (>750 k) in 1° infxn
• At least 1 time HIV screening recommended for all adult Pts (MMWR 2006;55:1)
• CD4 count: not a dx test, b/c can be HIV w/ normal CD4 or be HIV 
w/ low CD4
Approach to newly diagnosed HIV Pt
• Document HIV infection; counseling re: treatment options, adherence & disclosure
• H&P (including focus on h/o OIs, STDs); review all current meds
• Lab evaluation: CD4 count, PCR, HIV genotype, CBC w/ diff., Cr, lytes, LFTs, A1c & fasting lipids; PPD or IGRA, syphilis & toxo screen & CMV IgG; HAV, HBV, & HCV serologies; Chlamydia & gonorrhea screen; baseline CXR; Pap smear/anal pap in 
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• ARVs should be given in consultation w/ HIV specialist (JAMA 2010;304:321)
• Counseling re: strict adherence to ARVs is essential; genotype prior to ART-initiation
• All HIV Pts should be considered for ARVs; strongly recommended initiate Rx for:
AIDS-defining illness, pregnancy, HIV-assoc. nephropathy, HCV/HBV co-infxn
CD4 £500/mm3 (NEJM 2009;360:1815 & 2011;365:193; DHHS 2012; http://aidsinfo.nih.gov)
Consider if CD4 >500; depends on Rx toxicity, adherence, potential for transmission
• Regimens for treatment-naïve Pts (DHHS guidelines Mar 29, 2012; http://aidsinfo.nih.gov)
[NNRTI + 2 NRTI] or [PI (± low-dose ritonavir) + 2 NRTI] or [II + 2 NRTI]
• Initiation of ARVs may transiently worsen existing OIs for several wks due to immune reconstitution inflammatory syndrome (IRIS)
Approach to previously established HIV Pt
• H&P (mucocutaneous, neurocognitive, OIs, malignancies, STDs); meds
• Review ARVs (past and current); if any must be interrupted, stop all to ↓ risk of resistance
• Failing regimen = unable to achieve undetectable viral load, ↑ viral load, ↓ CD4 count or clinical deterioration (with detectable viral load consider genotypic or phenotypic assay)
COMPLICATIONS OF HIV/AIDS
Fever
• Etiologies (Infect Dis Clin North Am 2007;21:1013)
infxn (82–90%): MAC, TB, CMV, early PCP, Histo, Crypto, Coccidio, Toxo, endocarditis
noninfectious: lymphoma, drug reaction. Non 1° HIV itself rarely (<5%) cause of fever.
• Workup: guided by CD4 count, s/s, epi, & exposures
CBC, chem, LFTs, BCx, CXR, UA, mycobact. & fungal cx, ✓ meds, ? ✓ chest & abd CT
CD4 <100–200 → serum crypto Ag, LP, urinary Histo Ag, CMV PCR or antigenemia
pulmonary s/s → CXR; ABG; sputum for bacterial cx, PCP, AFB; bronchoscopy
diarrhea → stool for fecal leuks, culture, O&P, AFB; endoscopy
abnormal LFTs → abd CT, liver bx (for pathology and culture)
cytopenias → BM bx (include aspirate for culture)
Cutaneous
• Seborrheic dermatitis; eosinophilic folliculitis; warts (HPV); HSV & VZV; MRSA skin & soft tissue infxns; scabies; candidiasis; eczema; prurigo nodularis; psoriasis; drug eruptions
• Dermatophyte infx: prox subungual onychomycosis (at nail bed); pathognomonic for HIV
• Molluscum contagiosum (poxvirus): 2–5 mm pearly papules w/ central umbilication
• Kaposi’s sarcoma (KSHV or HHV8): red-purple nonblanching nodular lesions
• Bacillary angiomatosis (disseminated Bartonella): friable violaceous vascular papules
Ophthalmologic
• CMV retinitis (CD4 usu <50); Rx: gan- or valganciclovir, ganciclovir implant or cidofovir
• HZV, VZV, syphilis (at any CD4 count) or Toxo: CD4 usually <100
Oral
• Aphthous ulcers; KS; thrush (oral candidiasis): curd-like patches typically w/ burning or pain; oral hairy leukoplakia: painless proliferation of papillae w/ adherent white coating usually on lateral tongue, caused by EBV but not precancerous
Endocrine/metabolic
• Hypogonadism; adrenal insufficiency (CMV, MAC, TB, HIV or med-related); wasting osteopenia/porosis (at all CD4 counts); fragility fractures
• Lipodystrophy: central obesity, peripheral lipoatrophy, dyslipidemia, hyperglycemia
• Lactic acidosis: N/V, abd pain; ? mitochondrial toxicity of AZT, d4T, ddI, other NRTI
Cardiac (JACC 2013;61:511)
• Dilated CMP (10–20%); PHT; CVD (NEJM 2003;348:702); pericarditis/effusion, VTE
Pulmonary
• Pneumocystis jiroveci (PCP) pneumonia (CD4 <200) (NEJM 1990;323:1444)
constitutional sx, fever, night sweats, dyspnea on exertion, nonproductive cough
CXR w/ interstitial pattern, ↓ PaO2, ↑ A-a ∇, ↑ LDH, PCP sputum stain, β-glucan
Rx if PaO2 >70: TMP-SMX 15–20 mg of TMP/kg divided tid, avg dose = DS 2 tabs PO tid
Rx if PaO2 <70 or A-a gradient >35: prednisone before abx (40 mg PO bid; ↓ after 5 d) Alternative Rx if sulfa-allergy or renal insufficiency
Gastrointestinal & hepatobiliary
• Esophagitis: Candida, CMV, HSV, aphthous ulcers, pills; EGD if no thrush or unresponsive to empiric antifungals
• Enterocolitis: bacterial (esp if acute: shigella, salmonella, C. diff); protozoal (esp. if chronic: Giardia, Entamoeba, etc.); viral (CMV, adeno); fungal (histo); MAC; AIDS enteropathy
• GI bleeding: CMV, KS, lymphoma, histo; proctitis: HSV, CMV, LGV, N. gonorrhoeae
• Hepatitis: HBV, HCV, CMV, MAC, TB, histo, drug-induced
• AIDS cholangiopathy: often a/w CMV or Cryptosporidium or Microsporidium (at ↓ CD4)
Renal
• HIV-associated nephropathy (collapsing FSGS); nephrotoxic drugs (incl TDF)
Hematologic/oncologic (Lancet 2007;370:59; CID 2007;45:103)
• Anemia: ACD, BM infiltration by infxn or tumor, drug toxicity, hemolysis
• Leukopenia; thrombocytopenia (bone marrow involvement, ITP); ↑ globulin
• Non-Hodgkin lymphoma: ↑ frequency with any CD4 count, but incidence ↑ with ↓ CD4
• CNS lymphoma: CD4 count <50, EBV-associated
• Kaposi’s sarcoma (HHV-8): at any CD4 count, incidence ↑ as CD4 ↓, usu. MSM
Mucocutaneous (red-purple nodular lesions); pulmonary (nodules, infiltrates, effusions, LAN); GI (bleeding, obstruction, obstructive jaundice)
• Cervical/anal CA (HPV); ↑ rates of liver (a/w HBV/HCV), gastric & lung CA
Neurologic
• Meningitis: Crypto (p/w HA, Δ MS, CN palsy ± meningeal s/s; dx w/ CSF; serum CrAg 90% Se), bact (inc. Listeria), viral (HSV, CMV, 1° HIV), TB, histo, Coccidio, lymphoma
• Neurosyphilis: meningitis, cranial nerve palsies, dementia, otic or ophtho s/s
• Space-occupying lesions: may present as HA, focal deficits or Δ MS. Workup: MRI, brain bx if suspect non-Toxo etiology (Toxo sero ) or no response to 2 wk of empiric anti-Toxo Rx (if Toxo, 50% respond by d3, 91% by d14; NEJM 1993;329:995)
• AIDS dementia complex: memory loss, gait disorder, spasticity (usually at CD4 ↓)
• Myelopathy: infxn (CMV, HSV), cord compression (epidural abscess, lymphoma)
• Peripheral neuropathy: meds, HIV, CMV, demyelinating
Disseminated Mycobacterium avium complex (DMAC)
• Fever, night sweats, wt loss, HSM, diarrhea, pancytopenia. Enteritis and mesenteric lymphadenitis if CD4 <150, bacillemia if <50. Rx: clarithromycin + ethambutol ± rifabutin.
Cytomegalovirus (CMV)
• Usually reactivation with ↓ CD4. Retinitis, esophagitis, colitis, hepatitis, neuropathies, encephalitis. Rx: ganciclovir, valganciclovir, foscarnet or cidofovir.