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POST EXPOSURE PROPHYLAXIS FOR HIV PEP

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POST EXPOSURE PROPHYLAXIS FOR HIV PEP Powered By Docstoc
					      POST EXPOSURE
      PROPHYLAXIS
      FOR HIV (PEP)
      27 August 2003
The Very Rev. Drew A. Kovach, M.D., M.Div.
         Director of HIV Services
        Kaiser Permanente Hawaii
              808.432.2383
         dkovach@hawaii.rr.com
Who Needs Treatment After
Exposure?
   Everyone!
   But not everyone needs medications
Where Do I Get Information?
PEPline
   The National Clinicians' Post-
    Exposure Prophylaxis Hotline
   1-888-448-4911
   24 hours a day; 7 days a week
   PEP Guidelines:
    http://www.ucsf.edu/hivcntr/Clinical_
    Resources/PEPGuidelines.html
http://www.ucsf.edu/hivcntr/Clinical_Resources/
Resources/PDFs/pep_steps.pdf
       Percutaneous Injuries
           Source Status   Class 1           Class 2      Class 3
Exposure   Description     Asymptomatic;     AIDS;        Pre-terminal
Level                      known low titer   symtomatic   AIDS; acute
                                             infection    HIV; high
                                                          titer
I          Superficial     OFFER             RECOMMEND    STONGLY
           Injury                                         ENCOURAGE

II         Visibly bloody RECOMMEND          RECOMMEND    STONGLY
           device used in                                 ENCOURAGE
           artery or vein
III        Deep/IM         STONGLY           STONGLY      STONGLY
           Actual          ENCOURAGE         ENCOURAGE    ENCOURAGE
           Injection
       Mucosal Exposures
         Source Status    Class 1       Class 2      Class 3

Exposure Description      Asymptomatic; AIDS;        Pre-terminal
Level                     known low     symtomatic   AIDS; acute
                          titer         infection    HIV; high titer
I        Small volume & OFFER           OFFER        OFFER
         brief contact

II       Large volume /   RECOMMEND     RECOMMEND    RECOMMEND
         prolonged
         contact
III      Large volume /   RECOMMEND     RECOMMEND    STONGLY
         prolonged                                   ENCOURAGE
         contact
      Cutaneous Exposures
           Source Status   Class 1              Class 2          Class 3

Exposure   Description     Asymptomatic; AIDS;                   Pre-terminal
Level                      known low     symtomatic              AIDS; acute
                           titer         infection               HIV; high titer

I          Small volume    OFFER                OFFER            OFFER
           &               Only if portal       Only if portal   Only if portal
           Brief contact   of entry             of entry         of entry

II         Large volume / OFFER;             OFFER;              OFFER;
           prolonged      RECOMMEND          RECOMMEND           RECOMMEND
           contact        if portal of entry if portal of        if portal of
                                                entry            entry

III        Large volume/   OFFER;               OFFER;           OFFER;
           prolonged       RECOMMEND            RECOMMEND        RECOMMEND
           contact         if portal of entry   if portal of     if portal of
                                                entry            entry
Standard Regimen
   Zidovudine (AZT, “Retrovir”) 200mg tid
   Lamivudine (3TC, “Epivir”) 150 mg bid
    Uses for Standard Regimen
   default regimen for initial triage
   good regimen when source patient has
    not been treated
   good regimen when HIV tests are
    pending
   probably a safe regimen for pregnant
    health care workers
    Advantages of Standard
    Regimen
   recommended by US Public Health Service
    (USPHS) for PEP
   AZT is associated with decreased odds of
    infection in the CDC case-control study of
    occupational HIV infection
   AZT has been used more than other drugs for
    PEP in health care workers
   side effects are predictable
   side effects are manageable
   serious toxicity is rare when used for PEP in
    health care workers
Advantages of Standard
Regimen
   AZT + 3TC may be active against some
    strains of AZT-resistant HIV
   can be given as a bid regimen can be given
    as a combination tablet (AZT +3TC
    “Combivir”) one tablet twice a day with food
Disadvantages of Standard
Regimen
   side effects are common; low adherence
   AZT is "unpopular" in some communities
   source patient may have resistant/cross-
    resistant HIV
   management and follow-up of patients with
    pre-existing anemia is more complicated
   delayed toxicity (oncogenic/teratogenic
    potential) unknown
Alternative Regimen
   Stavudine (D4T, Zerit) 40mg bid
    (if < 60 kg use 30mg bid)
   Lamivudine (3TC, Epivir) 150mg bid
Potential Uses for Alternative
Regimen
   exposed patient is unable to tolerate
    AZT
   desire to use a regimen less likely to
    cause side effects
Advantages of Alternative
Regimen
   very well-tolerated in patients with HIV
    infection; good adherence
   serious toxicity appears to be rare in patients
    with HIV infection
   bid regimen
   may be effective against HIV strains from
    source patients who are taking AZT
   very active regimen in patients with HIV
    infection
Disadvantages of Alternative
Regimen
   not currently explicitly recommended for PEP
    by USPHS
   no data demonstrate effectiveness for PEP
   source patient may have resistant/cross-
    resistant HIV
   delayed toxicity (oncogenic/teratogenic
    potential) unknown
   minimal data about experience when used for
    PEP in health care workers
Potential Uses of Protease
Inhibitors
   source patient is taking one of the drugs in
    the standard or preferred alternate dual
    combination regimen (especially when
    resistance is suspected)
   exposure is especially risky (very large
    volume, high titer)
   exposed patient and/or treating clinician
    strongly prefer this option
Advantages of Protease
Inhibitors (all theoretical)
   drug with a second mechanism of action may
    enhance efficacy of PEP
   triple drug regimens are more active in HIV-
    infected patients than are dual drug regimens
    and the same could be true for PEP
   in case PEP fails, it may be better to have
    health care worker on a three-drug regimen
    during seroconversion
 Disadvantages of Protease
Inhibitors
   no data demonstrate that protease inhibitors
    are active for PEP
   no data demonstrate that adding a protease
    inhibitor will increase PEP efficacy
   source patient may have resistant HIV
   class resistance - if source patient is resistant
    to one, may be resistant to all
   drug-drug interactions complicate treatment
   serious toxicities (diabetes, nephrolithiasis)
    can occur
Disadvantages of Protease
Inhibitors
   side effects common; anticipate low
    adherence
   add to complexity of treatment regimen;
    anticipate low adherence
   relatively new; spectrum of toxicities may be
    incomplete
   delayed toxicity (oncogenic/teratogenic
    potential) unknown
   minimal data about experience when used for
    PEP in health care workers
Choice of Protease Inhibitor
   Indinavir (IND, Crixivan) 800mg tid on
    an empty stomach
   Nefinavir (NFV, Viracept) 750mg tid
    with meals
Indinavir (Crixivan)
   potent HIV inhibitor
   should drink 8 glasses of fluid /day to
    prevent nephrolithiasis
   hyperbilirubinemia and  LFT’s not rare
    (avoid IND during late pregnancy)
   otherwise well-tolerated
Nefinavir (Viracept)
   diarrhea is common; give Lomotil
    prescription
   otherwise well-tolerated
   best choice for use in combination with
    DDI regimens
Non-nucleoside Reverse
Transcriptase Inhibitors
   Efavirenz (EFV; Sustiva) 200mg 3 at hs
Potential Uses of NNRTIs
   Consider in cases where the source
    patient is on other antiviral drugs and
    no other options are sensible (especially
    when resistance is suspected)
   Consider when the exposed person
    cannot tolerate the drugs used in the
    above regimens
Advantages of NNRTI’s
   do not require phosphorylation before
    activation, and may be active earlier than
    other reverse transcriptase inhibitors (this is
    likely to be only a theoretical advantage of no
    clinical benefit?)
   are commonly used now as often as PI’s
Disadvantages of NNRTI’s
   these drugs are associated with rash (early
    onset) that can be severe
   differentiating between early NNRTI rash and
    acute infection can be difficult and cause
    extraordinary concern for the exposed person
   minimal data about experience when used for
    PEP in health care workers
   delayed toxicity (oncogenic/teratogenic
    potential) unknown
   CNS side effects of Efavirenz
Common Questions
     “What is the risk for getting HIV
     after a needlestick, an injury with a
     sharp instrument, or a splash?”
   About 1 in 300, or 0.3%
   Less than 0.1% if post-exposure
    medication taken
   The risk for infection from a bloody
    splash to mucous membranes or to
    open skin is very low - less than 1 in
    1000
Specific Factors Increase the Risk

   an exposure to blood from a terminally-
    ill AIDS patient
   an exposure caused by a needle which
    was used in a blood vessel
   an exposure caused by a visibly-bloody
    device
   a deep puncture
“Can treatment after exposure
prevent HIV infection?”
   workers who took only AZT after
    needlestick exposures to HIV was 79%
    lower than those who were not treated.
   The CDC issued new treatment
    recommendations for HIV exposures in
    2001 (MMWR, June 29, 2001). AZT+
    3TC after serious exposures to HIV.
    “Is it true that some people have
    taken AZT after an exposure
    and still become infected?”


   Yes; 19 published cases in the world
   We don’t however, know how many
    were exposed took medication and did
    not get infected
“Why are both AZT & 3TC being
recommended after HIV exposures?”


   Due to AZT resistant virus being
    common
   Monotherapy is not used for HIV
    treatment
“What about adding
other drugs?”
   In special serious exposure cases or
    when resistant HIV is suspected
   Protease inhibitors and NNRTI’s can be
    considered with expert consultation
    “What are the side effects of
    treatment?”
   66% had some side effects with
    AZT + 3TC
       Headache
       Nausea and vomiting
       Fatigue
   70% had side effects with PI’s
       Liver toxicity
       Kidney stones
       Diarrhea and abdominal distress
“When should treatment be started?”
   As soon as possible
   Within 1-2 hours
   When in doubt start
   Treatment can be stopped when
    risk/benefits have been determined
“How long does treatment last after
an exposure?”

   28 days
Summary Of
Recommendations
   Offer   continued supportive care
   Offer   compassion & understanding
   Offer   guidance
   Offer   hope
In Conclusion...
   Prevention is the best approach!
   Don’t recap needles!
   Wash area with soap and water!
   Seek counseling and health care at
    once!
MAHALO!

				
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