Natural History of HIV Infection - Timeline of Progression Acute: • Viral Transmission

Natural History of Syphilis Primary - 2-6 weeks after infection • Chancre, Regional lymphadenopathy Early Latent ≤ 1 year after infection • Asymptomatic Secondary - 1-2 months after primary syphilis • Rash, Fever, Generalized lymphadenopathy, Mucosal lesions, Alopecia, Hepatitis, Nephritis Late Latent - > 1 year after infection • Asymptomatic Early Neurosyphilis → Late Neurosyphilis Tertiary Syphilis - 2-50 years after infection • Gummatous disease (15%); Cardiovascular syphilis (10%); Ocular syphilis; Otic syphilis; Meningovascular disease, meningomyelitis, general paresis, tabes dorsalis (5%) #Syphilis #timeline #progression #diagnosis #stages

Lung Infections in HIV - Differential Diagnosis Framework Disease by CD4 Count: Any CD4 Count: • Mycobacterium tuberculosis, Bacterial pneumonia • Seasonal influenza CD4 <200: • Pneumocystis jirovecii pneumonia (PJP), MAI, Cryptococcal pneumonia, Extrapulmonary tuberculosis, Blastomycosis CD4 <50-100: • Toxoplasmosis • Histoplasmosis, Coccidioidomycosis, CMV, Mycobacterium avium, Mycobacterium kansasii, Invasive aspergillosis, Rhodococcus equi, Pseudomonas FUNGAL PNEUMONIAS: • Weight loss, lethargy, fever • Disseminated • Pleuritic CP • Cough, dyspnea • (Less common since cART) Aspergillus Pneumonia: • 3 syndromes: ABPA, Mycetoma, Invasive Aspergillosis • High fever, cough, and dyspnea, wheezing • Pleuritic chest pain may be present. Hemoptysis (occasionally massive) - angioinvasive disease. • CT: Halo sign Coccidioides Immitis Pneumonia: • "Flu-like", Valley fever • Fever, weight loss, Lymphadenopathy, Chest pain, cough • Polymorphic skin lesions (papules, pustules, erythematous nodules, plaques) Cryptococcus Neoformans Pneumonia: • Cough and dyspnea • Lobar consolidation or nodular infiltrates PJP Pneumonia: • Risk: Can produce significant depression of the phagocytic function of alveolar macrophages in HIV • Lung Exam: Can be normal • Fever (It's usually low if you have HIV), Chills, Dry cough or wheezing, Shortness of breath, Fatigue, Chest pain or tightness when you breathe, Weight loss Histoplasma Capsulatum Pneumonia: • (Fever, weight loss), Lymphadenopathy, dry cough or dyspnea, hepatomegaly, • Oral mucosal ulcers, erythema nodosum or erythema multiforme, • Multiple skin lesions (pustules, crusted papules), • Cytopenias VIRAL PNEUMONIAS: Influenza: • Rapid onset of a "flu-like syndrome" consisting of dry cough, myalgias, headache and high fever CMV: • 2-4 week subacute course • Nonproductive cough, dyspnea, and fever BACTERIAL PNEUMONIAS: Most Common: • Streptococcus pneumoniae - 20% of pneumonias • Haemophilus influenzae - 10-15% of pneumonias • Staphylococcus aureus Nocardia Pneumonia: • Chest pain, cough, bloody sputum, sweats, chills, weakness, lack of appetite, weight loss • Imaging: Irregular nodules or infiltrates-necrotizing • Lung most commonly infected M. Tuberculosis Pneumonia: • Upper lung zone infiltrates • Cavities • Fever, chills, night sweats, anorexia, productive cough, and occasional hemoptysis • Lymphadenopathy, CNS involvement MAI Pneumonia: • Constitutional symptoms (fever, weight loss, anorexia) Hepatosplenomegaly, lymphadenopathy, • Abdominal pain, chronic diarrhea, cytopenias M. Kansasii Legionella: • Nausea, vomiting, and diarrhea • Hyponatremia • Elevated hepatic transaminases • C-reactive protein levels >100 mg/L • Rhabdomyolysis (rare) Co-MRSA Pneumonia: • PVL virulence factor • May cause rapidly progressive necrotizing pneumonia Rhodococcus Equi Pneumonia: • Indolent course with fever, cough and cavitary infiltrates, mimicking TB Chlamydia Pneumoniae: • Focal pneumonia, pleural effusion, or bronchitis Mycoplasma Pneumoniae: • Cough (reported in 100% of cases), anemia, arthralgia, dyspnea, sore throat along with fever, rales, interstitial infiltrates or lobar pneumonia Coxiella Burnetii: • Fever, headache, non-productive cough, myalgia • Lung nodules possible in HIV PARASITIC PNEUMONIAS: • Toxoplasma gondii - Fever, nonproductive cough, and dyspnea • Strongyloides stercoralis - Worms in lungs • Cryptosporidium, and Microsporidium #Lung #Infections #HIV #AIDS #pulmonary #differential #diagnosis #infectiousdiseases

Acute Retroviral Syndrome Acute Retroviral Syndrome is the symptomatic presentation of acute human immunodeficiency virus infection • Presents as a mononucleosis/flu type of syndrome with a constellation of nonspecific symptoms • >50,000 HIV infections occur annually in the US • 10 to 60% - No symptoms • Time: 2-4 weeks from exposure to symptoms • May last days or weeks • Virus infects wide variety of tissues, seeds the lymphoid organs • Symptoms of primary HIV typically begin within 28 days of infection Acute Retroviral Syndrome Symptoms: • Headache (45%) • Fever (75%) • Encephalopathy (25%) • Fatigue (68%) • Lymphadenopathy (39%) • Photophobia (24%) • Mouth ulcers • Sore throat (40%) • Night sweats (28%) • Skin rash (48%) • Hepatomegaly - Liver enzyme elevation • Nausea, vomiting, diarrhea (27%) • Myalgias, Arthralgias (49%) • Weight loss (>5 lb; 2.5 kg) (32%) Atypical Presentations: • Opportunistic infections - rare during transient CD4 lymphopenia of early HIV infection - Most common: Oral and esophageal candidiasis • Central nervous system manifestations Labs: • CD4+ T-cell count can decrease (<200 cells per microliter or <14%), in which case opportunistic infections can develop • Viral RNA level ↑ • Leukocyte-lymphocyte subset counts ↓ • Liver enzymes ↑ • Mild anemia • Thrombocytopenia Neuro - Aseptic Meningitis: • >1 in 10 patients have symptoms • Severe headache, meningismus • Photophobia • Lymphocytic pleocytosis on cerebrospinal fluid DDX: • Epstein-Barr virus (EBV) • Cytomegalovirus (CMV) • Toxoplasmosis • Rubella • Syphilis • New onset SLE • Disseminated gonococcal infection • Viral hepatitis Diagnosis: Fourth-generation HIV-1/2 Immunoassay • Detects both HIV antibody and HIV p24 antigen • Identify acute/early infection in up to 80% of patients • HIV-1 p24 core Ag - Detects 17-20 days after exposure • Antibodies to HIV-1 and HIV-2 • HIV-1 RNA viral load Confirmatory Tests: • HIV-1/HIV-2 differentiation immunoassay • If differentiation IA is indeterminant - then an HIV Nucleic Acid test is necessary Eclipse Phase: • The short interval following HIV acquisition in which no diagnostic test is capable of detecting HIV for 10-12 days. • HIV RNA is the first test to detect HIV (10 days after initial HIV-1 acquisition,) • 17-20 days after exposure: HIV p24 antigen detected • 21 to 25 days after exposure, HIV-1 or HIV-2 antibodies can be detected (IgG/IgM-sensitive HIV-1 antibody test) Treatment: • ART to slow HIV disease progression by slowing CD4 decline and reducing HIV RNA levels. #Acute #Retroviral #Syndrome #HIV #diagnosis

Immune Reconstitution Inflammatory Syndrome - Overview of IRIS What Is IRIS? • A state of hyperinflammatory response that usually occurs in the first six months of treatment of HIV/AIDS patients. • The newly reconstituted immune system may react more strongly to an existing infection, causing a worsening of that disease. Paradoxical IRIS: • The worsening of a previously diagnosed opportunistic infection after initiating antiretroviral therapy. Unmasking IRIS: • Worsening of an unrecognized infection with exaggerated inflammatory features after initiating antiretroviral therapy. Who Gets It? • 10-20% of HIV-infected patients starting on antiretroviral therapy ART: • ART ↓ viral load within the first 1 to 2 weeks after initiation • ART ↑ improves CD4 count in 3-6 months IRIS: Generally Diagnosis of Exclusion! No specific diagnostic criteria, but the following should be present: • AIDS with low pretreatment CD4 count (<100), except TB IRIS which can occur at any CD4 count! • Virologic and immunologic response to ART with a decrease in HIV-1 RNA level from baseline or an increase in CD4+ cells from baseline or both • Rule out drug-resistant infection, bacterial superinfection, drug reactions, noncompliance • Clinical manifestations of inflammation • Temporal association between ART initiation and onset of illness features - One week to a few months (median 48 days) Severity of IRIS Depends On: • CD4 count before ART initiation • Degree of viral suppression • CD4 recovery after ART initiation Clinical Presentation: • Related to the type and location of preexisting opportunistic infection • The physical findings of IRIS depend on the pathogen involved Pathogens: • M. TB - Lymphadenitis, pulmonary infiltrates, pleural effusions, CNS tuberculoma meningitis, pericarditis, peritoneal disease, osteitis, cutaneous lesions, serositis peritonitis, bowel perforation, epididymitis, granulomatous nephritis, fevers • MAC/NTM - Painful lymphadenitis, pulmonary infiltrates, peritonitis, osteomyelitis, cutaneous abscesses, cavitation • Cryptococcus species - Meningoencephalitis, lymphadenitis, cryptococcomas, cavitating pneumonia, skin lesions, ocular • PJP - Pneumonitis (fever, cough, hypoxia, and pulmonary infiltrates), organizing PNA • Mycobacterium Leprae - Cutaneous lesions • Histoplasmosis - Lymphadenitis, cutaneous histoplasmosis, mucocutaneous • JC Virus - Progressive multifocal leukoencephalopathy (PML), Confusion, visual symptoms such as double vision, blindness, or gait ataxia • Papillomavirus - Molluscum contagiosum • Herpes Simplex Virus - Genital ulceration • Varicella Zoster - Zoster flare, ocular lesions: keratitis, iritis • CMV - Retinitis, immune recovery uveitis, Extraocular symptoms: pneumonitis, colitis, pancreatitis • HBV, HCV - Hepatic flare, rapid progression of cirrhosis. Fever, chills, lack of appetite, unintentional weight loss, nausea, jaundice. • Kaposi sarcoma, HHV8 - Worsening of cutaneous lesions with swelling, tenderness, and peripheral edema Other Pathogens Associated with IRIS: • Parvovirus B19 • Candida albicans • Epstein Barr Virus • Herpes simplex • Bartonella henselae • Histoplasma capsulatum • Dermatophytosis • Leprosy • Bacillus Calmette-Guérin (BCG) • Talaromyces (Penicillium) marneffei • Schistosoma mansoni • Molluscum contagiosum virus • Leishmaniasis Differential Diagnosis: • Drug reaction/ART toxicity • Poor adherence to treatment • Persistently active infection/drug resistance • New opportunistic infection Treatment: • ART is usually continued when patients develop IRIS (exception: encephalitis secondary to IRIS) - Use NSAIDs or corticosteroids for IRIS • Treat for opportunistic infection ASAP • Paradoxical IRIS: • Therapy for previous infection continued • If already on ART, continue ART, use NSAIDs or corticosteroids for IRIS with severe symptoms • No need to prevent IRIS by delaying ART treatment, unless the patient has known cryptococcal or TB meningitis • Guidelines recommend starting ART < 2 weeks for most OI • Cryptococcal meningitis: ART 4-6 weeks after antifungal therapy (COAT TRIAL: Deferring ART for 5 weeks improved survival) • TB meningitis: ART should be delayed at least four weeks (and initiated within eight weeks) after treatment for TB meningitis is initiated. Corticosteroids should be considered adjuvant treatment #IRIS #Immune #Reconstitution #Inflammatory #Syndrome #Differential #Diagnosis #Management