Transcript HIV and the Surgeon

HIV and the Surgeon
Paul MacPherson PhD, MD, FRCPC
Assistant Professor of Medicine
Division of Infectious Diseases
Ottawa Hospital, General Campus
University of Ottawa
Summary
1.
2.
3.
4.
5.
6.
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
Today’s Reality
HIV: A Global Pandemic
6,850/day
285/hour
5,753/day
240/hour
Current Demographics in Canada
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)
HIV Epidemiology
Developing World
– Heterosexual men and women
– Children
Developed World
–
–
–
–
–
Men who have sex with men
People from endemic countries
Aboriginals
People who use injection drugs
Heterosexual men and women
HIV Transmission
Transmission
1. Sexual contact with exchange of bodily fluids
–
Exposure of mucous membranes
2. Sharing injection drug paraphernalia
–
Needles, snorting straws
3. Transfusion of infected blood or blood products
–
Currently 1 in 500,000
4. Mother to child (vertical)
–
Perinatal and breast feeding
Sexual Transmission of HIV:
HIV is contained in:
– Semen
– Vaginal secretions
– Rectal secretions
– (Saliva at very low levels)
Exposure to HIV
In these fluids:
1. HIV is present as
free virus
2. HIV is contained in
infected CD4 cells
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.
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
Mucous Membrane: rectum
• Lymphoid follicles: 15/cm2 in the colon and increase
to 25/cm2 in the rectum.
Mucous Membrane: the target
M-cells transport HIV directly
into the lymphoid follicle
Owen, RL. Pathobiology, 1998.
Mucous Membrane: cervix
• Lymphoid follicle in the cervix. CD4 cells are stained
brown.
Kobayashi, Am J Pathology, 2002
Mucous Membrane: the target
Hladik F. Immunity, 2007.
McCoombe. AIDS, 2006.
Transmission: Injection drug paraphernalia
Sharing injection drug paraphernalia
• Access to clean needles
• Drug rehabilitation programs
Transmission: Blood transfusion
Transfusion of infected blood or blood products
• Screening donated blood
– ELISA: 2-3 month window period
– PCR: essentially no window period
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.
Virus
Human Immunodeficiency Virus
HIV and Immunology
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
Clinical
Natural History of HIV Disease
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 10 - 12 years
• the competency of the immune system is
reflected by the CD4 count
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”
CD4 Count
What is the CD4 count?
800-1000 is normal
>500 no worry
200-500 a bit of a gray zone.
<200 at risk
<50 at significant risk
Risk of Illness based on CD4 Count
>500: usually no symptoms. May have fever, night
sweats, lymphadenopathy, weight loss
200-500: recurrent HSV, zoster, sinusitis, pneumonia
candidiasis (oral, vaginal), lymphoma
<200: PCP, Toxo, KS, Cryptococcus
<50: MAC, CMV, PML, dementia, wasting
Cerebral Toxoplasmosis
Progressive Multifocal Leucoencephalopathy
CNS Lymphoma
Cryptococcal Meningitis
CMV Retinitis
Pneumocystis jeroveci pneumonia
Tuberculosis
Oral candidiasis
Esophageal Candidiasis
Kaposi’s Sarcoma
Bacillary angiomatosis
•
•
•
•
Red papular skin lesions
Bartonella henselae
CD4 < 50
Rx: Doxycycline
Macrolide
Zoster
• VZV reactivation
• Acyclovir IV
Molluscum contagiosum
•
•
•
•
•
Umbilicated papules
Pearly in appearance
CD4 < 100
Rx: Liquid nitrogen
Rx: HAART
Eosinophilic Folliculitis
• CD4 < 200
• Waxing and waning
• Moderate to severe
pruritis
• 90% occur above T2
• Rx: topical steroids
Seborrheic dermatitis
• Erythematous plaques
with greasy scales
• Face, ears, scalp, axilla
• Topical steroids with or
without ketoconazole
HIV-Associated Wasting Syndrome
Antiretroviral Therapy
The new era
Antiretrovirals
Save Lives
Antiretrovirals reduce the rate of progression
No treatment
Antiretrovirals
years
Why Antiretroviral Therapy?
Why Antiretroviral Therapy?
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!
Antiretrovirals
Antiretrovirals:
NRTI’s
Abacavir
Didanosine (EC)
Emtricitabine
Lamivudine
Stavudine (XR)
Tenofovir
(Zalcitabine)
Zidovudine
Combivir (AZT+3TC)
Kivexa (ABC+3TC)
Truvada (TDF+FTC)
NNRTI’s
Efavirenz
Nevirapine
Delavirdine
Etravirine
Other
T20
Maraviroc
Raltegravir
Prot Inh’s
Amprenavir
Atazanavir
Indinavir
Lopinavir
Nelfinavir
Ritonavir
Saquinavir
Tipranavir
Darunavir
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
Adverse Drug Effects
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
Adverse Effects: Lipodystrophy Syndrome
1. Hyperlipidemia:
•
•
•
Total cholesterol, LDL and triglycerides
Risk of atherosclerosis
Pravastatin, Crestor and Fibrates are drugs of choice
2. Lipodysmorphic Features
–
–
Fat atrophy of face and limbs
Fat accumulation dorsocervical pad, stomach, breasts
3. Insulin Resistance
•
May consider metformin
Mother to child transmission
Transmission of HIV from mother to infant
occurs predominantly at the time of
delivery.
Women and Infant Transmission Study, 1999
Viral Load
< 1000
1000 – 10,000
10,000 – 50,000
50,000 – 100,000
> 100,000
Transmission
0%
16.6%
21.3%
30.9%
40.6%
Average risk of transmission to the infant: 30%
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%
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
2008
Indications for surgery in HIV+ patients
Indications for Surgery: not on therapy
• Intracranial lesion
–
–
–
–
–
–
Primary CNS lymphoma
Toxoplasma
TB
Gumma
PML
Bacterial abscess
• Stereotactic needle biopsy
Indications for Surgery: not on therapy
• Lymph node biopsy
– lymphoma, TB, MAC
• Cholecystitis
– Cholelithiasis
– Crytosporidium, CMV, MAC
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)
Plastic Surgery
Lipoatrophy
HIV and Surgical Outcomes
HIV + ARV = excellent surgical outcomes
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. 2006 Nov; 93(11):1383-9.
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.
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. 2005 Sep;13(3):167-9.
No significant differences in complication rates were
found among HIV-infected women compared with
uninfected women.
ARV and Surgery
HIV-positive renal recipients can achieve
survival rates similar to those of HIVnegative patients.
Terasaki Foundation Laboratory, Los Angeles, CA, USA.
Transplantation. 2006 Jun 27;81(12):1658-61.
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)
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. 2006 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. 2005 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.
Occupational Exposure
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
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
Needle stick Injuries
What do we worry about?
1) Hepatitis B: 30% risk
- chronic hepatitis, cirrhosis, carcinoma
2) Hepatitis C: 3% risk
- chronic hepatitis, cirrhosis, carcinoma
3) HIV: 0.3% risk
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.
Risk Assessment:
1) You
2) The patient
3) The Injury
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
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
The Patient:
Do know:
1) HIV: what is the viral load?
how sick is the patient?
2) HepB: is he/she sAg+
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?
Post Exposure Prophylaxis
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
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
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
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
Hepatitis C
• Takes up to three months to develop antibodies
• HCV RNA detectable in blood within
7 - 14 days
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
Infection Control
and HIV
Protecting Yourself
Protecting Yourself and Others
What body fluids contain HIV?
Protecting Yourself and Others
What body fluids contain HIV?
Blood
semen
vaginal fluids
Protecting Yourself and Others
What body fluids do not contain HIV?
Saliva
Tears
Sweat
Urine
Stool/diarrhea
Vomit
*unless contaminated with blood
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)
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!!
The new face of HIV