HIVAIDS M3 lecture

1
HIV/AIDS M3 lecture

• Angela Remington, MD MS
• Fellow Infectious Diseases
• Updated 2005

2
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

3
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

4
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

5
MTCT of HIV

• Developing countries 40
• On Zidovudine alone 7
• Zidovudine with C-section 2
• HAART
• 80 of those infected vertically are infected
  close to the time of delivery

6
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

7
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

8
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

9
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

10
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

11
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

12
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

13
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

14
AIDS

• CD4
• Pneumocystis pneumonia
• Esophageal Candidiasis
• Mucocutaneous herpes simplex
• Miliary/extrapulmonary TB
• Cryptosporidium
• HIV-associated wasting
• Microsporidium
• Peripheral neuropathy

15
AIDS

• CD
• Cerebral toxoplasmosis
• Non-Hodgkins lymphoma
• Cryptococcal meningitis
• HIV-associated dementia
• Primary CNS Lymphoma
• Progressive multifocal leukoencephalopathy

16
AIDS

• CD4
• CMV retinitis, gastroenteritis
• Disseminated Mycobacterium avium complex

17
Diagnosis

• Antibody test, ELISA
• Western blot
• HIV RNA viral load

18
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
• Kaposis sarcoma
• Molluscum contagiosum
• Bacillary angiomatosis

19
(No Transcript)
20
(No Transcript)
21
(No Transcript)
22
GI disease

• Esophageal candidiasis
• Large bowel disease (bloody diarrhea)
• C. diff
• CMV
• Small bowel disease (watery diarrhea)
• Cryptosporidium
• Microsporidium
• Giardia
• MAC
• CMV

23
Pulmonary Disease

• Pneumocystis pneumonia
• Bacterial pneumonia
• Nocardia

24
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 will have pneumonia annually
• Prophalaxis started at CD4 trimethoprim/sulfa, dapsone, atovaquone,
  pentamidine

25
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

26
Nervous system disease

• Toxo
• Crypto
• PML
• CMV retinitis
• Dementia
• Peripheral neuropathy

27
Management

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

28
antiretrovirals

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

29
NRTIs

• ddC
• ddI
• 3TC
• ZDV
• d4T
• Abacavir
• FTC

30
NNRTIs

• Nevirapine
• Efavirenz
• Delavirdine

31
PIs

• Indinavir
• Saquinavir
• Ritonavir
• Nelfinavir
• Lopinavir/ritonavir
• Amprenavir
• Fosamprenavir
• Tipranavir
• Atazanavir

32
Others

• T-20
• Tenofovir
• R5/X4 under development

33
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