Transcript HIV/AIDS M3 lecture - Creighton University

HIV/AIDS
M3 lecture
Angela Remington, MD MS
Fellow Infectious Diseases
Updated 2005
Introduction
AIDS first recognized 1981
 HIV RNA retrovirus discovered 1983
 2nd leading cause of disease burden
worldwide
 Leading cause of death in Africa
 Approx 1 million people currently
diagnosed in America
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Transmission of HIV
Blood, semen, breast milk, saliva
 Sexual, parenteral, vertical
 Risk of contracting infection dependent on
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– Viral load
– Integrity of the exposed site
– Type of body fluid
– Volume of body fluid
Transmission of HIV
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Risk after a single exposure
– >90% blood or blood products
– 14% vertical
– 0.5-1% injection drug use
– 0.2-0.5% genital mucous membrane
– <0.1% non-genital mucous membrane
MTCT of HIV
Developing countries 40%
 On Zidovudine alone 7%
 Zidovudine with C-section 2%
 HAART <1% if viral load <50 copies
 80% of those infected vertically are
infected close to the time of delivery
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Transmission
Risk of transmission is now 1/10,000,000
with each unit of blood
 100 confirmed cases from healthcare
exposure
 Risk with needle stick 0.32%
 Risk with mucous membrane exposure
0.03%
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global
Estimated 42 million people living with
HIV/AIDS in 2002
 5 million new infections per year
 3 million deaths per year
 Parts of Africa 25-40% of adults are
infected
 85% heterosexual transmission worldwide
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The Virus
Glycoproteins (gp 120, gp41)
2 copies of ssRNA, viral enzymes
Attachment with gp 120 to CD4 receptor
Fusion mediated by gp 41
Inside cell RNA transcribed to DNA by RT
DNA incorporated into cell genome
DNA is copied and translated to viral enzymes,
proteases
 New infectious virus buds from host cell to
repeat process
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Immunology
Gradual reduction in number of circulating
CD4 cells inversely correlated with the
viral load
 Any depletion in numbers of CD4 cells
renders the body susceptible to
opportunistic infections
 Lymphatic tissue (spleen, lymph nodes,
tonsils/adenoids) main reservoir of HIV
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Primary Infection
70-80% symptomatic, 3-12 weeks after
exposure
 Fever, rash, cervical lymphadenopathy,
aseptic meningitis, encephalitis, myelitis,
polyneuritis
 Surge in viral RNA copies to >1 million
 Fall in CD4 count to 300-400
 Recovery in 7-14 days
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Seroconversion
3-12 weeks, median 8 weeks
 Level of viral load post seroconversion
correlates with risk of progression of
disease
 Differential for this syndrome: EBV, CMV,
Strep pharyngitis, toxoplasmosis,
secondary syphilis
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Asymptomatic phase
Remain well with no evidence of HIV
disease except for generalized
lymphadenopathy
 Fall of CD4 count by about 50-150 cells
per year
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Symptomatic phase
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Mild impairment of immune system
Chronic weight loss
Fever
Diarrhea
Mild candida infections
Recurrent herpes infections
Pelvic inflammatory disease
Bacillary angiomatosis
Cervical dysplasia
AIDS
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CD4 <200
– Pneumocystis pneumonia
– Esophageal Candidiasis
– Mucocutaneous herpes simplex
– Miliary/extrapulmonary TB
– Cryptosporidium
– HIV-associated wasting
– Microsporidium
– Peripheral neuropathy
AIDS
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CD <100
– Cerebral toxoplasmosis
– Non-Hodgkin’s lymphoma
– Cryptococcal meningitis
– HIV-associated dementia
– Primary CNS Lymphoma
– Progressive multifocal leukoencephalopathy
AIDS
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CD4<50
– CMV retinitis, gastroenteritis
– Disseminated Mycobacterium avium complex
Diagnosis
Antibody test, ELISA
 Western blot
 HIV RNA viral load
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Skin and Oral disease
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Seborrheic dermatitis
Xeroderma
Itchy folliculitis
Scabies
Tinea
Herpes zoster
Papillomavirus
Oral and vaginal candidiasis
Oral hairy leukoplakia
Aphthous ulcers
Herpes simplex
Gingivitis
Kaposi’s sarcoma
Molluscum contagiosum
Bacillary angiomatosis
GI disease
Esophageal candidiasis
 Large bowel disease (bloody diarrhea)
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– C. diff
– CMV
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Small bowel disease (watery diarrhea)
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Cryptosporidium
Microsporidium
Giardia
MAC
CMV
Pulmonary Disease
Pneumocystis pneumonia
 Bacterial pneumonia
 Nocardia
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Pneumocystis pneumonia
Most common AIDS presenting illness
 Reactivation of infection (original airborne
transmission, asymptomatic, early age)
 Inversely correlated with CD4 count
 40% of patients with CD4 <100 and not
prophalaxed will have pneumonia annually
 Prophalaxis started at CD4 <200,
trimethoprim/sulfa, dapsone, atovaquone,
pentamidine
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Pneumocystis pneumonia
2-3 week history of SOB and dry cough
 Hypoxemia
 Perihilar ground glass appearance on CXR
 Silver stain of organism in sputum
 High dose trimethaprim/sulfa, steroid if
hypoxic
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Nervous system disease
Toxo
 Crypto
 PML
 CMV retinitis
 Dementia
 Peripheral neuropathy
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Management
Treatment recommended when
symptomatic or CD4 count below 200
 Earlier if high viral load, rapidly falling CD4
count, hepatitis C co-infection
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antiretrovirals
Nucleoside reverse transcriptase inhibitors
 Non-nucleoside reverse transcriptase
inhibitors
 Protease inhibitors
 Fusion inhibitors
 R5/X4 inhibitors
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NRTIs
ddC
 ddI
 3TC
 ZDV
 d4T
 Abacavir
 FTC
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NNRTIs
Nevirapine
 Efavirenz
 Delavirdine
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PIs
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Indinavir
Saquinavir
Ritonavir
Nelfinavir
Lopinavir/ritonavir
Amprenavir
Fosamprenavir
Tipranavir
Atazanavir
Others
T-20
 Tenofovir
 R5/X4 under development
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Side effects
NRTIs: mitochondrial dysfunction
ddC, ddI, d4T: neuropathy
 d4T, ddI: hepatic steatosis, lactic acidosis
 ddI: pancreatitis
 ZDV: anemia
 d4T: fat atrophy
 Abacavir: hypersensitivity reaction
 Tenofovir: renal failure
 NNRTIs: rash, liver toxicity
 PIs: fat redistribution, insulin resistance, hyperlipidemia
 Indiavir: renal stones
 Nelfinavir: diarrhea
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