Snapshot A 36-year-old woman is admitted to a hospital in India with a three-week history of fever, headache, and increasing drowsiness. Past medical history reveals she was diagnosed with pulmonary TB nine months ago. She is in the continuation phase of her anti-TB regimen. On exam, patient is pale and emaciated. There are coarse crackles in both lung fields. She is disoriented to time, person, and place but responds to commands. Kernig sign is positive. A complete blood count revealed a hematocrit of 30%, WBC of 12,500 cells/mm3, with 84% neutrophils. Urinalysis, basic metabolic profile, and liver function tests were within normal limits. Sputum for AAFB was negative. A HIV screen was positive and this was confirmed with a Western blot. CD4 count was 57 cells/μL. Fundoscopy was normal. Chest radiograph revealed bilateral opacities in both lung fields. CT scan of the brain was normal. CSF analysis revealed lymphocytes 64 cells/mm3, protein 84mg/dL and glucose 31 mg/dL. Gram and Ziehl-Neelsen stains were negative. CSF for India ink stain was positive for Cryptococcus neoformans. Introduction Classification (+) ssRNA retrovirus HIV Presentation CD4 < 400 cells/μL constitutional symptoms ("wasting syndrome") weight loss fever night sweats adenopathy bacterial infections M. tuberculosis H. influenzae S. pneumoniae Salmonella Nocardia may cause TB-like pulmonary cavitations oral thrush (Candida albicans) tinea pedis reactivation VZV CD4 < 200 cells/μL PCP (Pnuemocystis jiroveci pneumonia) Cryptococcus neoformans Cryptosporidium Coccidioidomycosis reactivation HSV Iospora CD4 < 100 cells/μL Toxoplasma gondii when patient presents with neurological findings next best step is imaging of the head (CT or MRI) if ring enhancing lesion is present the next best step is empiric treatment with pyrimethamine-sulfadiazine if treatment fails, biopsy of lesion is necessary Histoplasmosis Candida albicans esophagitis Candida is the most common cause of esophagitis in late HIV Kaposi Sarcoma eruption of violaceous plaques could be indicative of HIV more common in men who have sex with men CD4 < 50 cells/μL blood M. avium-intracellulare CMV retinitis and esophagitis Cryptococcus neoformans meningoencephalitis HIV in the neonate (a ToRCHeS infection) recurrent infections oral thrush interstitial pneumonia chronic diarrhea lymphopenia HIV encephalitis HIV crosses BBB via infected macrophages results in inflammation in the brain appearance of microglial nodules with multinucleated giant cells occurs late in the course of HIV infection AIDS dementia complex mental status changes depression ataxia seizures urinary and bowel incontinence Serous otitis media from obstructive lympadenopathy/lymphomas Evaluation Diagnosis of HIV ELISA is the first step in diagnosis high false-positive rate (high sensitivity and low specificity) rules OUT the possibility of infection HIV 1/2 differentiation assay best confirmatory test returns result more quickly than a Western blot Western blot is then used to confirm positive results high false-negative rate (low sensitivity and high specificity) rules IN the diagnosis of infection Both tests detect antibodies to HIV proteins antibodies take 3-6 weeks to develop tests can be falsely negative in first 1-2 months of infection tests can be falsely positive in babies born to infected mothers anti-gp120 crosses placenrta the presence of viral RNA or antigens (e.g. p24) can also be tested directly Diagnosis of AIDS CD4+ ≤ 200 cell/ul (normal: 500-1500 cells/ul) CD4+ percentage <14% HIV positive with AIDS-associated infection e.g., P. jiroveci pneumonia Viral load tests PCR used to monitor effects of therapy on viral load high viral load associated with poor prognosis Differential Other causes of immune suppresion cancer chemotherapy organ transplant patients congenital immuonodeficiencies Treatment Over 25 HIV drugs exist in multiple categories CCR5 inhibitors fusion inhibitors reverse transcriptase inhibitors integrase inhibitors protease inhibitors Highly active antiretroviral therapy (HAART) combines multiple drugs with multiple mechanisms of action to prevent resistance e.g., tenofovir + emtricitabine + efavirenz or many other possible combinations Pregnancy use zidovudine (ZDV and AZT) to prevent mother-to-fetus transmission efavirenz and delavirdine are thought to be teratogenic HIV is an absolute contraindication to breastfeeding in the United States Prognosis, Prevention, and Complications Prognosis has improved but depends on multiple factors most important access to proper drug treatment poor prognostic factors include high viral RNA loads CD4 count < 200 cells/μL Prevention no effective HIV vaccine available for exposure: obtain HIV serology and immediately initiate three-drug antiretroviral therapy vaccination against secondary infection pneumococcal vaccine is indicated in HIV-positive patients live vaccines are contraindicated in HIV-positive patients MMR and Varicella can be given IF CD4 count is >200 cells/μL blood secondary prevention involves prevention of opportunistic infection CD4 count used to determine need for prophylaxis < 200 cells/μL TMP-SMX for Pneumocystis pneumonia < 100 cells/μL TMP-SMX for toxoplasmosis < 50 cells/μL azithromycin for M. avium-intercellulare Complications may be due to HIV infection or side effects of HAART dyslipidemia glucose intolerance/diabetes mellitus cardiovascular disease