Download Occupational Blood Related Transmission

Prophylaxis for Blood
(Occupational) and Sexual
HIV Exposures
Allen McCutchan, M.D., M.Sc.
Revised from material supplied by
Jennifer Blanchard, M.D.
Exposure Risk - What’s an exposure?
Violation of skin barrier by HIV containing fluids
from
– Penetrating injuries (needle sticks)
– Mucous Membrane contact
– Contact with – chapped, abraded, or inflamed skin or
with an open wound
Rarely, if ever, from sharing personal grooming
tools like toothbrushes or razors
Not from contact with intact skin because HIV
does not penetrate healthy skin
Exposure Risk - Exposed to what?
What fluids ?
– Blood
– Body fluids
Semen (fluids from several glands)
Vaginal secretions (vaginal fluid, cervical mucus,
and menstrual blood)
Rarely Others( not Saliva, tears, sweat, or
nonbloody feces or urine) unless bloody
What viruses– HIV and Hepatitis B and C
Risk Factors for Transmission:
Exposure to more HIV (or Hep B or C)
 Exposure to larger quantity of blood




Needle placed directly in artery or vein
Deep injury
Hollow-bore needle
Device visibly contaminated with patients
blood
 Patients with higher viral load
 Acutely infected (primary HIV infection)
 Terminally ill
Exposure Risk:
Patient Factors
Known HIV+
– Viral load
– On therapy
Unknown HIV status
– History of risk factors
– Symptoms c/w primary HIV
– History of HIV testing
Unknown patient (ie. sharps box stick)
– Prevalence where exposure occurred
– How long sharp exposed
Exposure Risk
Not all needlesticks are the
same
Average risk for needlestick is 0.3% (1 HIV
infection / 300 needle sticks)
Average risk for mucous membrane
exposure is 0.09% (1 HIV infection / 9000)
As of 6/00, CDC had received 56 reports
of HCW’s with seroconversion (this is
likely a serious underestimate)
Exposure Risk
Not all needlesticks are the same
Risk factor
Deep injury
Adjusted odds
ratio*
16.1
Visible blood on device
5.2
Procedure involving needle
in artery or vein
5.1
Terminal illness in source
patient
6.4
Postexposure use of ZDV
0.2
*All were significant at p<0.01
PEP or no PEP
Most exposures do not result in
transmission of HIV
Consider
– risk of exposure and
– Infectivity of the source patient
Consider health of HCW
If Source’s Serostatus is
Unknown
PEP until lab results obtained and then
modify or discontinue
Get consent for testing from source
patient
Test source patient and assess risk
factors for window period (HIV without
HIV antibody)
Legal Issues in Testing
Unknown Patients
Source patient’s consent is not required to tell
HCW of known HIV status
Source pts MD must make “good faith” effort
to obtain consent to test for HIV
Testing may proceed without pts consent and
results given to exposed HCW
Patient must be informed of this and may
elect not to receive results.
HCW must maintain confidentiality
Primary Prevention
Don’t get stuck
– Never recap
– Sedate the patient if necessary and
possible
– Wear gloves
Don’t get splashed
– Wear glasses or goggles
The Rationale for Postexposure
Prophylaxis
Systemic infection does not occur
immediately, leaving theoretical “window of
opportunity” to modify viral replication
Animal data on PEP
– ARV may block dissemination from dendritic cells
to susceptible T cells
– ARV may prevent intravenous infection of T cells
Human data on PEP is limited but supportive
Primary HIV infection –
Rhesus Monkeys & SIV
Rhesus monkeys exposed intravaginally with
SIV
At 24 hours, SIV detected in vaginal dendritic
cells
These cells fuse with CD4 lymphocytes and then
migrate to regional lymph nodes
By 48 hours, SIV detected in inguinal LNs
Lymphatic spread of virus and infected cells to
the spleen and other lymphoid tissues
By 5 days, SIV detected in the blood
Primary HIV Infection
Human Data
Viral dynamics in acute HIV infection in
humans were similar to the SIV model
Time from mucosal infection to initial
viremia varies from 4-11 days
After infection, there is a rapid rise in
plasma viremia, with widespread
dissemination of the virus ass’d with
seeding of lymphoid organs
Primary HIV Infection
Human Data
Viral doubling time in acute HIV ~ 12 hours
Peak HIV RNA levels were detected 12-29
days post exposure (mean 21 days)
Rise in viral load exceeds 1 million RNA
molecules/mL
Drop in viral load ass’d with appearance of
cytotoxic T lymphocytes
Viral set point is then established
Animal PEP
Mice and AZT
SCID mice inoculated IV with HIV
AZT PEP initiated 0.5, 1,2,4,8,24,36, & 48h
later
All mice treated at 0.5, 1, & 2 h were
protected
80% treated at 8h protected
40% treated at 24 h protected
No protection of treatment started at 48h.
Shih CC et al. JID 1991
Animal PEP
Tenofovir and Macaques
IV SIV inoculation to long-tailed
macaques
Tenofovir given
– 48 hours before
– 4 & 24 hours after
– For 28 days
No treated animals infected; all controls
infected
Tsai CC et al. Science,1995;270: 1197-1199
Animal PEP
Tenofovir and Macaques
Macaques infected IV with SIV
3,10 or 28d PEP with tenofovir initiated
at 24, 48, & 72 hours after inoculation.
All controls infected
All animals treated at 24h for 28d
protected
50% showed persistent viremia in other
treatment groups.
Tsai CC et al. J Virology 1998;72:4265-73.
Summary of Animal PEP
Prophylactic Efficacy
Decreased with large viral inocula
Decreased with delay
– Best results within 24 hours
Decreased with shortened duration
– 4 weeks ass’d with highest protection
– 3 & 10 days not protective for macaques
exposed to SIV
Decreased with lower dose PEP
Increased with normal host immune
system
Human PEP - Efficacy
No prospective studies
Retrospective case-control studies, risk
of HIV infection was reduced by 80% in
those who took AZT as PEP
ACTG 076 – maternal-fetal transmission
decreased by 67%
Numerous studies of decreased
perinatal transmission with ARVs
Case reports
Indications for PEP for Injuries
PEP Indicated
High risk exposure
Known + patient
AIDS/high viral load
No delay to rx
PEP not indicated
Low risk exposure
Low risk pt
Found needle
Delay > 72 hours
Drug interactions/
coexisting medical
problems
Human PEP for Blod
Transfusions
13 y/o girl transfused 1 unit of packed red
cells from donor in the “window period”
Infection risk estimated to be 100%
3-drug PEP initiated at 50 h posttransfusion, continued for 9 mo
No evidence of HIV infection 15 mo later
– Ann Int Med 2000;133:31-4
Limitations of the Data
Very difficult to study human primary
infection
Extrapolating animal data to humans
Maternal-fetal transmission is not the
same as occupational exposures
PEP Drugs
2 or 3 drugs based on risk of
exposure/pt
– AZT/3TC
– AZT/3TC + Lopinavir/ritonavir + 1 dose
nevirapine
– Modify based on source pt/drug resistance
Important goal is completing 4 week
regimen
– 50% stop b/c source pt HIV– 50% stop d/t side effects
PEP Drugs – Side Effects
N/V/D, hepatitis
Nephrolithiasis
Anemia, Neutropenia
Headache, Rash
Pancreatitis
Hyperglycemia
Hyperbilirubinemia
Hypersensitivity reactions
Other…
PEP Drugs – Side effects
Is it worth it?
– 50% of HCW have side effects
– No long term data on carcinogenesis
1/3 of HCW’s discontinue PEP d/t side effects
Most side effects reversible or modifiable
– Anti-emetics, anti-diarrheals
– Epogen
Nevirapine: Serious Adverse
Events
MMWR 1/5/01 report of 22 cases of severe
toxicity in people taking NVP for PEP from
3/97 through 9/00
Clinical syndromes reported:
– 12 cases of hepatoxicity (2 fulminant hepatitis, 1
required liver transplant)
– 14 cases of skin reactions (1 Stevens-Johnson)
– 1 case of rhabdomyolysis
Not recommended for long term use unless
exposure high risk, high risk of MDR virus,
HCW with no liver hx and EFV
contraindicated
Pregnant HCW
Pregnancy should not preclude the use of
postexposure prophylaxis
Less data on safety of PI’s in first trimester
Sustiva contraindicated
Avoid IDV near term d/t hyperbilirubinemia in
newborns
D4T/ddI contratindicated d/t mitochondrial
toxicity in newborns
Drugs usually started after 14 weeks gestation
in chronically infected pts if not already on
ARVs
Drug Resistant Virus
Very little data
Combination regimens recommended
based on data for chronically infected
individuals
Resistance testing not helpful
Use agents that the source has not been
exposed to
PEP Failures
21 cases reported
16 AZT monotherapy
2 AZT/ddI
3 with > drugs (AZT/3TC/IDV;
AZT/3TC/ddI/IDV)
13/21 source pts previously treated with
ARVs
4/7 resistance assays showed
decreased sensitivity to PEP meds used
HIV Infection in HCW’s
81% experienced syndrome c/w primary
HIV infection at median of 25d
Median time to seroconversion 46d
Factors implicated in failure
– Viral resistance
– Large inoculum
– Delayed or shortened PEP
Management of Occupational
Exposure to HIV
Wash wound with soap and water; flush mucous
membranes with water, saline or sterile wash
Initiate PEP immediately (can be modified later)
– Pregnancy test
HIV Ab testing at baseline, 6 weeks, 12 weeks, 6
months & 1 year
HIV PCR RNA ? (not recommended by CDC)
– High false + rate (2-5%)
– Only if symptomatic
CBC, Chem 10,liver panel baseline and 2 weeks
Counseling and education
Counseling: Weeks 1-12 after
exposure
Abstain from sex or use condoms
Do not donate blood, semen, organs
Consider stop breast-feeding
Seek medical care for any acute illness
that occurs during the follow up period
– Acute HIV infection
– Drug reaction
– Other
Acute Retroviral Syndrome
Symptoms start within a few to many
weeks after exposure, but could also
represent drug reactions
May last few days to more than 10
weeks; average < 14 days
Severe or prolonged symptoms
correlate with more rapid disease
progression
Signs and Symptoms
Fever
Fatigue
Rash
Headache
Lymphadenopathy
Pharyngitis
Myalgias, arthralgias
>80-90%
>70-90%
>40-80%
32-70%
40-70%
50-70%
50-70%
Signs and Symptoms – Acute
HIV Infection
N/V/D
Night sweats
Aseptic meningitis
Oral/genital ulcers
Thrombocytopenia
Leukopenia
Elevated LFTs
30-60%
50%
24%
5-20%
45%
40%
21%
Signs and Symptoms – Acute
HIV Infection
Thrush
Weight loss
Depression
Retro-orbital pain
Rash – maculopapular, involves the trunk
What to do if you are exposed
Wash wound with soap and water
Flush mucous membranes with
saline/water
Determine status of source patient
Test source patient
Take the meds as soon as possible
– Normal working hours - Pam Scott in
occupational health - pager 1447
– After hours - ED