This document provides an overview of HIV/AIDS, including its discovery in 1981, transmission routes, global prevalence, diagnosis, disease progression as CD4 counts decline, opportunistic infections, treatment with antiretrovirals, and potential side effects of treatment. It describes the virus itself and the immunological response. Key points are that transmission risk depends on viral load and type/volume of bodily fluid exposure, and treatment is generally recommended once symptomatic or if CD4 is below 200.

1. HIV/AIDS
M3 lecture
Angela de padre, MD
Yashar Najiaghdam, MD
Fellow Infectious Diseases
Updated 2011-2012

2. 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

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
– <0.1% non-genital mucous membrane

5. 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

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

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

16. AIDS
 CD4<50
– 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
 Kaposi’s sarcoma
 Molluscum contagiosum
 Bacillary angiomatosis

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 <100 and not
prophalaxed will have pneumonia annually
 Prophalaxis started at CD4 <200,
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