1. HIV and the Surgeon Paul MacPherson PhD, MD, FRCPC
Assistant Professor of Medicine
Division of Infectious Diseases
Ottawa Hospital, General Campus
University of Ottawa

2. Summary
HIV today
HIV infection and natural history
Current treatments for HIV infection
Indications for surgery in HIV+ patients
Surgical outcomes for HIV+ patients
Needlestick injuries

3. Today’s Reality

4. HIV: A Global Pandemic

7. 6,850/day
285/hour

9. 5,753/day
240/hour

10. Current Demographics in Canada

11. Demographic Trends 1. HIV+ tests (all ages) highest in 1995 at 2,990
lowest in 2000 at 2,106
increased in 2001 and 2002 and then plateaued at 2,500
2. Increasing among older adults (age >40 yrs)
3. HIV+ tests among MSM: increasing since 2001
4. Steady decline among injection drug users
5. Steady increase among Heterosexuals
68% increase in Ontario over the past 5 years (11%/yr)

15. HIV Epidemiology Developing World Developed World
Heterosexual men and women
Children
Developed World
Men who have sex with men
People from endemic countries
Aboriginals
People who use injection drugs

16. HIV Transmission

17. Sexual contact with exchange of bodily fluids
Transmission
Sexual contact with exchange of bodily fluids
Exposure of mucous membranes
Sharing injection drug paraphernalia
Needles, snorting straws
Transfusion of infected blood or blood products
Currently 1 in 500,000
Mother to child (vertical)
Perinatal and breast feeding

18. Sexual Transmission of HIV:
HIV is contained in:
Semen
Vaginal secretions
Rectal secretions
(Saliva at very low levels)

19. Exposure to HIV
In these fluids:
HIV is present as free virus
HIV is contained in infected CD4 cells

20. Mucous Membranes: the target
Mucous membranes are the moist epithelial linings of body cavities including the:
oral cavity
rectum
vagina and cervix
inner foreskin
Live cells line the surface.

21. Mucous Membrane: the target
Only 2% of the body’s immune cells circulate in the blood
98% of the body’s immune cells are located in the lymph nodes and the mucous membranes
Mucous membranes are rich in T-cells and macrophages to provide defence
The majority of these cells are organized into “lymphoid follicles” just under the surface of the mucosal membrane

22. Mucous Membrane: rectum
Lymphoid follicles: 15/cm2 in the colon and increase to 25/cm2 in the rectum.

23. Mucous Membrane: the target
M-cells transport HIV directly
into the lymphoid follicle
Owen, RL. Pathobiology, 1998.

24. Mucous Membrane: cervix
Lymphoid follicle in the cervix. CD4 cells are stained brown Kobayashi, Am J Pathology, 2002

25. Mucous Membrane: the target
Hladik F. Immunity, 2007.
McCoombe. AIDS, 2006.

26. Transmission: Injection drug paraphernalia
Sharing injection drug paraphernalia
Access to clean needles
Drug rehabilitation programs

27. Transmission: Blood transfusion
Transfusion of infected blood or blood products
Screening donated blood
ELISA: 2-3 month window period
PCR: essentially no window period

28. Transmission: Mother to child
Mother to child (vertical)
In utero (trans-placental)
Peri-natal accounts for majority of cases
By blood-blood mixing
Breast feeding.

29. Virus

30. Human Immunodeficiency Virus

32. HIV and Immunology

33. Immunologic: Peripheral Blood
CD4 T-cells: infected, decrease, dysfunction, alterations in subsets
CD8 T-cells: dysfunction, anergic, alterations in subsets
Macrophages: infected, dysfunction
NK cells: dysfunction
B-cells: dysfunction- polyclonal hypergammaglobulinemia
Cytokine dysregulation
Lymph Nodes
Hyperplastic and eventually fibrotic

34. Clinical

35. Natural History of HIV Disease

36. HIV Disease HIV enters the body and slowly destroys the immune system
without treatment, HIV is continuously active
without treatment, the average length of time between infection and the onset of symptomatic disease is years
the competency of the immune system is reflected by the CD4 count

37. Viral Load What is the viral load? How much virus per ml of blood
Range 100’s to >500,000
Viral load and progression are roughly correlated
Each patient has their own “set-point”

38. CD4 Count What is the CD4 count? 800-1000 is normal >500 no worry
a bit of a gray zone.
<200 at risk
<50 at significant risk

39. Risk of Illness based on CD4 Count
>500: usually no symptoms. May have fever, night
sweats, lymphadenopathy, weight loss
: recurrent HSV, zoster, sinusitis, pneumonia candidiasis (oral, vaginal), lymphoma
<200: PCP, Toxo, KS, Cryptococcus
<50: MAC, CMV, PML, dementia, wasting

41. Cerebral Toxoplasmosis

42. Progressive Multifocal Leucoencephalopathy

43. CNS Lymphoma

44. Cryptococcal Meningitis

45. CMV Retinitis

46. Pneumocystis jeroveci pneumonia

47. Tuberculosis

48. Oral candidiasis

49. Esophageal Candidiasis

50. Kaposi’s Sarcoma

51. Bacillary angiomatosis
Red papular skin lesions
Bartonella henselae
CD4 < 50
Rx: Doxycycline
Macrolide

52. Zoster
VZV reactivation
Acyclovir IV

53. Molluscum contagiosum
Umbilicated papules
Pearly in appearance
CD4 < 100
Rx: Liquid nitrogen
Rx: HAART

54. Eosinophilic Folliculitis
CD4 < 200
Waxing and waning
Moderate to severe pruritis
90% occur above T2
Rx: topical steroids

55. Seborrheic dermatitis
Erythematous plaques with greasy scales
Face, ears, scalp, axilla
Topical steroids with or without ketoconazole

56. HIV-Associated Wasting Syndrome

57. Antiretroviral Therapy The new era

58. Antiretrovirals
Save Lives

59. Antiretrovirals reduce the rate of progression
No treatment
Antiretrovirals
years

61. Why Antiretroviral Therapy?

62. Why Antiretroviral Therapy?

63. Treatment Goals Maximal viral suppression (VL<50)
Undetectable does not mean absent
Durable suppression
Restoration and preservation of immune function
Improved quality of life
Reduction in morbidity and mortality
Current projected life-expectancy from time of diagnosis: 43 years!

64. Antiretrovirals

65. Antiretrovirals: NRTI’s NNRTI’s Prot Inh’s
Abacavir Efavirenz Amprenavir
Didanosine (EC) Nevirapine Atazanavir
Emtricitabine Delavirdine Indinavir
Lamivudine Etravirine Lopinavir
Stavudine (XR) Other Nelfinavir
Tenofovir T20 Ritonavir
(Zalcitabine) Maraviroc Saquinavir
Zidovudine Raltegravir Tipranavir
Combivir (AZT+3TC) Darunavir
Kivexa (ABC+3TC)
Truvada (TDF+FTC)

66. First Line Combinations (DHHS):
Protease Inhibitor-Based Regimens:
ABC/TDF + 3TC/FTC + Kaletra (LPV/rit)
ABC/TDF + 3TC/FTC + ATZ/rit
ABC/TDF + 3TC/FTC + SQV/rit
ABC/TDF + 3TC/FTC + DRV/rit
NNRTI-Based Regimens:
ABC/TDF + 3TC/FTC + EFV
Avoid
d4T + AZT
d4T + ddI
3TC + emtricitabine

67. Adverse Drug Effects

68. Adverse Effects: Drug Specific
AZT: marrow suppression, nausea
d4T: neuropathy, lactic acidosis and lipodystrophy
Abacavir: hypersensitivity reaction
Tenofovir: renal failure
Didanosine: peripheral neuropathy, pancreatitis
Efavirenz: CNS symptoms, sleep disturbance
Nevirapine: rash, hepatotoxicity
Atazanavir: hyperbilirubinemia
Lopinavir: diarrhea
Saquinavir: GI intolerance
Indinavir: nephrolithiasis

69. Adverse Effects: Lipodystrophy Syndrome
Hyperlipidemia:
Total cholesterol, LDL and triglycerides
Risk of atherosclerosis
Pravastatin, Crestor and Fibrates are drugs of choice
Lipodysmorphic Features
Fat atrophy of face and limbs
Fat accumulation dorsocervical pad, stomach, breasts
Insulin Resistance
May consider metformin

71. Mother to child transmission

72. Transmission of HIV from mother to infant occurs predominantly at the time of delivery.

73. Women and Infant Transmission Study, 1999
Viral Load Transmission
< %
1000 – 10, %
10,000 – 50, %
50,000 – 100, %
> 100, %
Average risk of transmission to the infant: 30%

74. ACTG 076 Study (1994) Protocol: AZT given IV during labour
AZT to the infant for 6 weeks
Success:
67.5% reduction in transmission
From 30% to 8.3%

75. Reducing Mother to Child Transmission:
If mother not diagnosed previously: perinatal AZT and C-section (risk < 5%)
If mother known HIV+: antiretroviral therapy beginning week 28
If mother known HIV+ and on antiretroviral therapy: continue therapy (change if on EFV)
If maternal VL < 50, then risk of perinatal transmission < 1%
Breast feeding only if no access to formula

76. 2008

78. Indications for surgery in HIV+ patients

79. Indications for Surgery: not on therapy
Intracranial lesion
Primary CNS lymphoma
Toxoplasma TB
Gumma
PML
Bacterial abscess
Stereotactic needle biopsy

80. Indications for Surgery: not on therapy
Lymph node biopsy
lymphoma, TB, MAC
Cholecystitis
Cholelithiasis
Crytosporidium, CMV, MAC

81. Indications for Surgery: on therapy
Coronary by-pass
Antiretrovirals associated with increased lipids
50% of HIV+ individuals smoke cigarettes
Increased rates of CVD
Resection of malignancies
Cervical cancer (HPV)
Anal cancer (HPV)
Lymphoma
Hepatoma
(No increase in breast or lung cancer)

82. Plastic Surgery

83. Lipoatrophy

84. HIV and Surgical Outcomes

85. HIV + ARV = excellent surgical outcomes

86. ARV and Surgery
Impact of highly active antiretroviral therapy on outcome of cholecystectomy in patients with human immunodeficiency virus infection.
Department of S. Siro Clinical Institute, University of Milan, Milan, Italy.
Br J Surg Nov; 93(11):
HAART was shown to be protective. A low HIV RNA load and a high CD4(+) cell count were significant predictors of uncomplicated surgical outcomes. CONCLUSION: HAART significantly reduces the risk of complications after cholecystectomy in patients with HIV infection.

87. ARV and Surgery
Outcomes of hysterectomy in HIV-seropositive women compared to seronegative women.
Department of Gynecology and Obstetrics, Emory University, Atlanta, USA.
Infect Dis Obstet Gynecol Sep;13(3):167-9.
No significant differences in complication rates were found among HIV-infected women compared with uninfected women.

88. ARV and Surgery
HIV-positive renal recipients can achieve survival rates similar to those of HIV-negative patients.
Terasaki Foundation Laboratory, Los Angeles, CA, USA.
Transplantation Jun 27;81(12):
Although not statistically significant, graft survival was higher among HIV-positive patients compared with their negative controls, as was patient survival.
Graft survival: 76.1% vs. 65.1% at 5 years (p=0.21)
Patient survival: 91.3% vs. 87.3% at 5 years (p=0.72)

89. ARV and Surgery
Excellent outcomes of cardiac surgery in patients infected with HIV in the current era.
Department of Cardiothoracic Surgery, Mount Sinai Medical Center, New York
Clin Infect Dis Aug 15;43(4):532-6.
The surgeon and AIDS: twenty years later.
Department of Surgery, Medical Center, University of California-Irvine, CA
Arch Surg Oct;140(10):961-7.
Since the first reports on indications and outcome for abdominal procedures in the HIV/AIDS patient were published 20 years ago, the epidemiology and presentation of surgical illness have changed remarkably with the advent of new antiviral regimens.

90. Occupational Exposure

91. Occupational Exposures
Pietrabissa et al (1997)
- surveyed 15,375 procedures in 39 hospitals by 122 surgeons over 6 months:
a) 3.9% of procedures had percutaneous or eye exposures
b) needle sticks accounted for 84% of injuries
c) 58% occurred at wound closure
d) direct correlation between length of procedure and number of injuries

92. Occupational Exposures
Prospective surveillance of HCW exposed to HIV conducted by CDC from 1983 to 1992:
89% percutaneous
5% mucous membrane
Of Percutaneous: 34% by syringe needles
40% by suture needles
4% by scaples
2% by lancets
4% other

93. Needle stick Injuries

94. What do we worry about? 1) Hepatitis B: 30% risk
- chronic hepatitis, cirrhosis, carcinoma
2) Hepatitis C: 3% risk
3) HIV: 0.3% risk

95. What do I do? 1) Don’t panic!
2) Dispose of the needle in a sharps container
3) Express blood from the wound
4) Clean thoroughly with Providone iodine, or chlohexidine, or soap and water
5) If eyes or mucous membranes: lots of water
6) Go to the Emergency Dept.

96. Risk Assessment:
1) You
2) The patient
3) The Injury

97. You: 1) Are you vaccinated against HepB? 2) Are you immune to HepB?
Get your titers measured!
3) General health
4) Blood work: CBC, lytes, liver function

98. The Patient: 1) HIV status 2) HepB status 3) HepC status
Don’t Know? Then request:
1) HIV test STAT, with consent from patient
2) HBsAg, HBsAb
3) HCV-Ab and PCR

99. The Patient: Do know: 1) HIV: what is the viral load?
how sick is the patient?
2) HepB: is he/she sAg+

100. The Injury: Risk Factors: depth of skin invasion?
Exposure to broken skin?
hollow bore or suture needle?
did the needle enter a blood vessel of the pt?
visible blood on the needle?
were you wearing gloves?

101. Post Exposure Prophylaxis

102. HIV Post Exposure Prophylaxis
There is minimal evidence for PEP:
1) case controlled study of HCW
2) ACTG 076, perinatal HIV transmission
3) Animal models

103. HIV Post Exposure Prophylaxis
AZT 300 mg BID
3TC 150 mg BID
Kaletra II tabs BID
should begin ASAP, within 48 hours of injury
total course = 28 days
side effects: nausea, vomiting, diarrhea, headache, fatigue, anemia, drug interactions

104. HIV Post Exposure Prophylaxis
Seen in clinic within 2 days
Repeat HIV tests at 1, 3 and 6 months
use condoms with all sex partners
do not donate blood
cost: $1200 for one month supply

105. Hepatitis B You should be vaccinated!
If not vaccinated and not immune,
liver function tests
HBIG and HepB vaccination
HBsAg and HBsAb at 1, 3 and 6 months

106. Hepatitis C Takes up to three months to develop antibodies
HCV RNA detectable in blood within
days

107. Hepatitis C
Recent trial of 44 health care workers exposed to HCV via needle sticks
received IFN daily for 1 month followed by IFN 3x per week for 5 months
95% response rate

108. Infection Control and HIV

109. Protecting Yourself

110. Protecting Yourself and Others
What body fluids contain HIV?

111. Protecting Yourself and Others
What body fluids contain HIV?
Blood
semen
vaginal fluids

112. Protecting Yourself and Others
What body fluids do not contain HIV?
Saliva Tears
Sweat Urine
Stool/diarrhea Vomit
*unless contaminated with blood

113. Protecting Yourself and Others
Wear gloves for venipuncture
Wear gloves for cleaning up any body fluids
Carefully dispose of sharps!!
Bedding, towels, etc stained with blood or vaginal fluids are laundered normally
No gowns! No masks! (except for bloody procedures)

114. Protecting the Patient
Do Not isolate because of HIV!!!
HIV+ individuals deserve your respect
If you don’t know about HIV, learn something
Maintain confidentiality!!

115. The new face of HIV