HIV/AIDS M3 LECTURE

HIV/AIDS
M3 lecture
Angela de padre, MD
Yashar Najiaghdam, MD

Fellow Infectious Diseases
Updated 2011-2012

Introduction
 AIDS first recognized 1981
 HIV RNA retrovirus discovered 1983
 2ndleading cause of disease burden
worldwide
 Leading cause of death in Africa
 Approx 1 million people currently
diagnosed in America

Transmission of HIV
 Blood, semen, breast milk, saliva
 Sexual, parenteral, vertical
 Risk of contracting infection dependent on
– Viral load
– Integrity of the exposed site
– Type of body fluid
– Volume of body fluid

Transmission of HIV
 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

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%

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

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

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

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

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

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

Symptomatic phase
 Mild impairment of immune system
 Chronic weight loss
 Fever
 Diarrhea
 Mild candida infections
 Recurrent herpes infections
 Pelvic inflammatory disease
 Bacillary angiomatosis
 Cervical dysplasia

AIDS
 CD4 <200
– Pneumocystis pneumonia
– Esophageal Candidiasis
– Mucocutaneous herpes simplex
– Miliary/extrapulmonary TB
– Cryptosporidium
– HIV-associated wasting
– Microsporidium
– Peripheral neuropathy

AIDS
 CD <100
– Cerebral toxoplasmosis
– Non-Hodgkin’s lymphoma
– Cryptococcal meningitis
– HIV-associated dementia
– Primary CNS Lymphoma
– Progressive multifocal leukoencephalopathy

AIDS
 CD4<50
– CMV retinitis, gastroenteritis
– Disseminated Mycobacterium avium complex

Diagnosis
 Antibody test, ELISA
 Western blot
 HIV RNA viral load

Skin and Oral disease
 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)
– C. diff
– CMV
 Small bowel disease (watery diarrhea)
– Cryptosporidium
– Microsporidium
– Giardia
– MAC
– CMV

Pulmonary Disease
 Pneumocystis pneumonia
 Bacterial pneumonia
 Nocardia

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

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

Nervous system disease
 Toxo
 Crypto
 PML
 CMV retinitis
 Dementia
 Peripheral neuropathy

Management
 Treatment recommended when
symptomatic or CD4 count below 200
 Earlier if high viral load, rapidly falling CD4
count, hepatitis C co-infection

antiretrovirals
 Nucleoside reverse transcriptase inhibitors
 Non-nucleoside reverse transcriptase
inhibitors
 Protease inhibitors
 Fusion inhibitors
 R5/X4 inhibitors

NRTIs
 ddC
 ddI
 3TC
 ZDV
 d4T
 Abacavir
 FTC

NNRTIs
 Nevirapine
 Efavirenz
 Delavirdine

PIs
 Indinavir
 Saquinavir
 Ritonavir
 Nelfinavir
 Lopinavir/ritonavir
 Amprenavir
 Fosamprenavir
 Tipranavir
 Atazanavir

Others
 T-20
 Tenofovir
 R5/X4 under development

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

HIV/AIDS M3 LECTURE

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