RNA virus: affects primarily CD4+ T-cells causing immune abnormalities, lymphopenia, autoimmune phenomena. Transmission occurs thru semen, vaginal secretions, blood or blood products, breast milk, and in utero transplacentally. No transmission has been documented to occur by casual contact.
RF: homosexuality/bisexuality, IVDA, heterosexual exposure, blood transfusion prior to 1985, maternal HIV infection
Acute retroviral syndrome: initial acute HIV infection. Flu-like illness – looks like mono. Occurs in 50-90% of pts. Develop 2-4 weeks after exposure. Fever (cyclic – afternoon/evening), fatigue, pharyngitis, rash, headache, oral ulcerations. Antibodies develop 3-8 weeks after infection, though can be longer. Usually become asymptomatic other than enlarged lymph nodes. Time from exposure to full-blown AIDS is 8.3 years and 2 years in children < 5yo. Viral load will be elevated in the acute phase, though unable to get result back in the ED.
Viral load and CD4+ T-cell count are used for HIV staging. Cocaine decreases CD4 production and increases viral reproduction up to 20x (Gruber, 2010).
Early infections, though not AIDS defining: thrush, vulvovaginal candidiasis, recurrent herpes zoster, ITP. Occur more frequently with CD4+ counts below 500.
AIDS: Defined by CDC by certain AIDS defining illnesses (Esophageal candidiasis, Cryptococcus, CMV retinitis, HSV, Kaposi sarcoma, Brain lymphoma, MAC, PCP, Brain toxoplasmosis, HIV encephalopathy, HIV wasting syndrome, Disseminated histoplasmosis, Isosporiasis, Disseminated Mycobacterium tuberculosis) or CD4+ count < 200. Advanced HIV occurs with CD4+ < 50 or disseminated MAC or CMV. AIDS-illnesses usually occur with either CD4+ < 200 or viral load > 50,000.
Can also look at total lymphocyte count to approximate CD4 count. < 1200 cells/mm with clinical symptoms are predictive of CD4+ < 200 (only 62% sensitivity though). ALC (total WBC x lymphocyte %): less than 1000 was 91% predictive of CD4 < 200 (67% sens, 96% spec); ALC < 2000 was 97% sensitive, 41% spec so ALC > 2000 was 95% predictive of CD4 > 200. (Shapiro, 1998).
HIV pts should not receive live vaccines (except MMR unless AIDS). Pneumococcal vaccine recommended >2yo. Influenza (inactivated) yearly.
Usually look for antibodies to HIV. ELISA (enzyme-linked immunosorbent assay): 99% specific and 98.5% sensitive. Western Blot: nearly 100% sensitive/specific. Acute HIV infection hard to detect since antibodies have not been formed yet. DNA PCR >99% sensitivity, viral load 95% sensitive, 95-100% viral culture sensitivity, 100% for most recent p24 antigen detection assays. Both p24 antigen and HIV RNA can be used for the acute phase.
Rapid HIV testing: UniGold Recombigen, Multispot HIV1/HIV2 Rapid Test, Reveal G3, OraQuick Advance HIV1/2 (only one FDA approved for oral fluid). Allow result to be given in 10-20 minutes. High sensitivity/specificity. Results come back preliminary positive; need confirmatory test with Western blot. Negative means negative – no further testing, though in early acute phase, may be false negative. Recent studies have shown a higher false-positive rate with rapid tests.
4th generation immunoassay: able to get positive within 2-4 weeks after infection, much faster than 3rd generation. Checks for possible antibodies and virus.
If CD4+ count > 500, generally have causes of fever similar to nonimmunocompromised pts. Counts 200-500, more likely to have bacterial respiratory infections. If < 200, common causes: early PCP pneumonia, central line infection, MAC infection, M. tuberculosis, CMV infection, drug fever, sinusitis. Non-infectious causes: neoplasm (non-Hodgkin lymphoma MCC) and drug fever. Send for serum cryptococcal antigen, blood fx for AFB
Disseminated MAC: CD4+ < 50-100. Fever, night sweats, weight loss, diarrhea. Goes to bone marrow causing anemia and high alk phos. Diagnosis by acid-fast stain blood culture. Use lysis-centrifugation is more sensitive for diagnosis. Tx: clarithromycin + ethambutol + rifabutin. Immune reconstitution illness to MAC: lymphadenitis after starting HAART. Continue HAART with antibiotics +/- steroids.
CMV: most common cause of serious viral dx in HIV. Commonly affects GI, pulmonary, CNS, retinitis.
Most common causes: AIDS dementia, Toxoplasma gondii, Cryptococcus neoformans. Need CT, then LP for most HIV patients with headache without clear alternative cause. If CD4 < 200, need to be even more aggressive. Noncontrast CT should be fine most of the time. CSF tests: opening pressure (crypto) cell count, glucose/protein, gram stain, India Ink stain (crypto), culture, viral culture, VDRL (syphilis), fungal culture, toxoplasmosis and cryptococcosis antigen assays, and coccidioidomycosis titer. Peripheral neuropathy (usually foot pain) can just be related to HIV, though can also be drug side effect. Also consider HSV, lymphoma, PML.
Symptoms to need CT (100% sens): new seizure, depressed/altered orientation, headache, different in quality than usual, prolonged headache (>3 days) (Rothman, 1999)
AIDS dementia: memory impairment / cognitive deficits. Occurs in 10-15% of HIV patients, more frequent if CD4 <100. Progressing disease. CT usually shows cortical atrophy and ventricular enlargement. CSF shows elevated protein. Gradually causes mental status changes, sometimes aphasia and motor abnormalities.
Toxoplasmosis: MCC focal encephalitis. Fever/headache/focal neuro/AMS/seizures. Most people have antibodies to it so serology not-useful though if negative, not toxo. CSF antibodies useful, though can be false negative. CT shows multiple subcortical lesions in basal ganglia. Contrast CT shows ring enhancing with edema (other causes of ring enhancing are lymphoma (usually single lesion with progressive symptoms over months, usually in the periventricular/corpus callosum), fungal, cerebral TB, though Toxo usually has multiple lesions). Tx: pyrimethamine + sulfadiazine + folinic acid (reduce pancytopenia). Dexamethasone 4mg q6hr reduces edema/mass effect. 20% of CT will have single lesion. Usually tx for toxo and if no improvement, will consider lymphoma.
Cryptococcosis: MC presenting sign: fever and headache, though can also have nausea, AMS, focal neuro deficits. Meningismus uncommon. Usually only if CD4<200. CSF: cryptococcal antigen testing (100% sens/spec) or india ink staining (60-80% sens). Usually have elevated ICP >25cm H20. Other CSF findings (cell count/protein/glucose) can be unremarkable. Serum cryptococcal antigen testing 95% sensitive. Tx: IV amphotericin B + oral flucytosine x 14d followed by 8 weeks fluconazole to clear CSF. Can have bone marrow suppression requiring lifelong fluconazole therapy.
MC abnormality is retinal microvasculopathy: cotton-wool spots similar to DM/HTN. Microaneurysms occur as well. Herpes zoster opthalmicus can also occur.
CMV Retinitis: Most frequent and serious ocular opportunistic infection in AIDS pts. Leading cause of blindness. Presents with visual acuity changes, visual field cuts, photophobia, scotoma (partial blind spot), eye redness, eye pain. Fundoscopic exam: fluffy white perivascular lesions with hemorrhage areas in them, ‘pizza pie’ or ‘cheese and ketchup’. Tx: Oral ganciclovir x 14-21 d +/- intraocular ganciclovir implants. Without detection, vision loss and blindness can occur. 10% still go blind.
HIV patients 2x more likely to have MI. Protease inhibitors (particularly long term) increase risk of MI.
Pneumocystis (PCP; P. jiroveci (new) or carinii (old)) pneumonia: MC opportunistic infection and MCC death among AIDS. Fever, nonproductive cough, SOB; usually gradual onset w/ fatigue. CXR: diffuse interstitial infiltrates, though 15-20% have neg findings. ABG will show alveolar-arterial gradient. High LDH > 220. Usual cause of hypoxia without other cause. Tx: Bactrim PO or IV x 3weeks. SE: rash, fever, neutropenia. Pentamidine alternative agent. If PaO2 < 70mm or A-a gradient > 35mm, give steroids (oral prednisone 40mg BID 3 week taper) (NNT 9-22). Or dapsone. 1/5 of compliant pts on PCP prophylaxis will still get it.
TB: 200-500x risk than general population. Usually occurs with CD4 200-500. Hemoptysis, night sweats, fever, weight loss, anorexia. Negative PPD common among late-stage AIDS. Diagnosis by sputum stain/culture. Need to have high suspicion in any AIDS patient due to high person/person transmission. Tx: 4-drug regiment (RIPE: Rifampin + Isoniazid + Pyrazinamide + Ethambutol). All HIV pts with +PPD should receive isoniazid + pyridoxine x 9-12mo (alt rifampin or rifabutin x 4mon).
Bacterial pneumonia still the MCC pulmonary infection in HIV patients. Disseminated fungal infection in severe immunosuppression: C. neoformans and Aspergillus fumigatus.
Candidiasis / Thrush: usually affects 90% of AIDS. Can be scraped off with erythematous base, usually on tongue/buccal mucosa. Hairy leukoplakia is usually adherent, white, thickened lesions on lateral tongue border – differentiate with KOH smear. When diagnosed in HIV, likely progression to AIDS. Oral/pharyngeal tx: Clotrimazole or nystatin suspension/troches 5x daily. Refractory cases: oral fluconazole. Severe: Amphotericin B. Odynophagia is basically esophagitis, usually in oral thrush pts with CD4 < 100. Tx: oral fluconazole or ketoconazole. Endoscope, biopsy, or IV caspofungin or amphotericin B for refractory cases. CMV and HSV can also be seen in the esophagus. Topical won’t work for esophageal form.
Diarrhea: Bacteria (shigella, salmonella, e.coli, entamoeba histolytica, campylobacter, MAC, Cdiff) – tx with cipro, parasites (giardia, cryptosporidium, isospora belli) – modified acid-fast stain, usually consult ID, viruses (CMV, HSV, HIV), fungi (H. capsulatum, C.neoformans). Usually unknown though. Drugs as well (nelfinavir and ritonavir). Late stage AIDS (CD4 < 100) can be related to CMV and MAC which need biopsy. AIDS-related enteropathy common as well. If profound GI bleeding, think CMV.
Proctatis: mainful defecation, rectal discharge. GC/C, Trepnema pallidum, HSV.
Low threshold to CT scan abdominal pain patient (may not have typical elevated WBC, peritoneal signs).
Kaposi Sarcoma: painless, raised, brown-black or purple papules/nodules that don’t blanch. Can be seen in oral cavity as well. No real tx, not associated with any worsening M&M.
Pruritic Papular Eruptions in HIV: presenting symptom in HIV in 25-75%; multiple, discrete red bumps which are pruritic, symmetric and diffusely distributed. Seen on extremities and trunk with sparing of mucous, palms, webspaces. Tx: steroids, emmollients, antihistamines. Usually resistant though.
HSV: can be more extensive than otherwise healthy pts. Herpes Zoster can be more complicated/prolonged. Disseminated or ophthalmic requires admission for IV acyclovir.
Scabies: scaly, persistent pruritic eruption, usually do not have classic intertriginous lesions. Tx: permethrin 5% cream x 1, ivermectin 200mcg/kg PO x 1, cortamiton. Norwegian scabies: more extensive version, less pruritic.
Usually 3 or 4 drugs: 2 nucleoside reverse transcriptase inhibitors + 1-2 protease inhibitors or 1 non-nucleoside reverse transcriptase inhibitor. Strongly recommended for CD4 < 350 or any hx/o AIDS defining illness, pregnancy, or co-infection with Hepatitis B. 6 classes of drugs now: NRTI (nucleotide reverse-transcriptase inhibitor, NNRTI (non-nucleotide reverse-transcriptase inhibitor), PI (protease inhibitor), FI (fusion inhibitor), INSTI (integrate strand transfer inhibitor), CCR5 (chemokine C-C motif receptor 5 antagonist).
HAART medications can decrease metabolism of some street drugs (Gruber, 2010).
Universal precautions with contact with blood/body fluids. Risk after parental exposure 0.32%, mucocutaneous exposure 0.09%. 80% of documented transmission have been with hollow-bore needle.
CDC: semen, vaginal fluid, CSF, synovial, pleural, peritoneal, pericardial, and amniotic fluid potentially infectious. Nasal or fecal, saliva, sputum, sweat, tears, urine, and vomitus are not considered potentially infectious unless they are visibly bloody.
Postexposure Propylaxis: One study found zidovudine prophylaxis reduced transmission by 79%. Risks for transmission: deep injury, visible blood on injuring device, needle placement in a vein or an artery of the source patient, source patient with late-stage HIV. Prophylaxis should be started within 1-2 hours, animal studies have shown little benefit if delayed by 24-36 hrs. CDC guidelines now recommend 3 drug regiment x 4 weeks over 2 drug regiment. Severe GI SE – 1/2 have SE, 1/3 will discontinue as a result.
CDC recommends prophylaxis for nonoccupational risk if < 72 hrs exposure with someone with known HIV. No prophylaxis with unknown HIV status source unless high risk for HIV. Consider in serious exposure if > 72hrs. All pts should be tested for antibodies initially, at 4-6 weeks, 3 months, and 6 months. 6 reported cases of transmission despite PEP. Antiretrovirals generally safe in first trimester (except EFV). No cases of transmission from source pt that is in the ‘window period.’
Preferred PEP regiment: FTC (emtricitabine) + TDF = Truvada combo + Raltegravir (RAL). ZDT can be used as alternative to TDF for renal failure pts and used with lamivudine (Combivir combo pill) instead of the others. Usually recommended 2 NRTIs + a INSTI, PI, or NNRTI. Other regiments should be consulted by ID.
References / Resources
Diagnosing and Treating HIV in the ED, Tim Lahey, Managing Medical Emergencies 2015, EMedHome