POST EXPOSURE PROPHYLAXIS FOR HIV PEP 27 August 2003

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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_at_hawaii.rr.com

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Who Needs Treatment After Exposure?

• Everyone!
• But not everyone needs medications

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Where Do I Get Information?
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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/Clinic
  al_Resources/PEPGuidelines.html

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http//www.ucsf.edu/hivcntr/Clinical_Resources/
Resources/PDFs/pep_steps.pdf
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Percutaneous Injuries
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Mucosal Exposures
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Cutaneous Exposures
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Standard Regimen

• Zidovudine (AZT, Retrovir) 200mg tid
  
  
  
• Lamivudine (3TC, Epivir) 150 mg bid

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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

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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

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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

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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

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Alternative Regimen

• Stavudine (D4T, Zerit) 40mg bid
  (if lt 60 kg use 30mg bid)
• Lamivudine (3TC, Epivir) 150mg bid

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Potential Uses for Alternative Regimen

• exposed patient is unable to tolerate AZT
• desire to use a regimen less likely to cause side
  effects

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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

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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

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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

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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

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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

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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

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Choice of Protease Inhibitor

• Indinavir (IND, Crixivan) 800mg tid on an empty
  stomach
• Nefinavir (NFV, Viracept) 750mg tid with meals

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Indinavir (Crixivan)

• potent HIV inhibitor
• should drink 8 glasses of fluid /day to prevent
  nephrolithiasis
• hyperbilirubinemia and ? LFTs not rare (avoid
  IND during late pregnancy)
• otherwise well-tolerated

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Nefinavir (Viracept)

• diarrhea is common give Lomotil prescription
• otherwise well-tolerated
• best choice for use in combination with DDI
  regimens

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Non-nucleoside Reverse Transcriptase Inhibitors

• Efavirenz (EFV Sustiva) 200mg 3 at hs

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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

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Advantages of NNRTIs

• 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 PIs

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Disadvantages of NNRTIs

• 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

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Common Questions
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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

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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

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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.

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Is it true that some people have taken AZT after
an exposure and still become infected?

• Yes 19 published cases in the world
• We dont however, know how many were exposed took
  medication and did not get infected

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Why are both AZT 3TC being recommended after
HIV exposures?

• Due to AZT resistant virus being common
• Monotherapy is not used for HIV treatment

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What about adding other drugs?

• In special serious exposure cases or when
  resistant HIV is suspected
• Protease inhibitors and NNRTIs can be considered
  with expert consultation

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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 PIs
• Liver toxicity
• Kidney stones
• Diarrhea and abdominal distress

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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

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How long does treatment last after an exposure?

• 28 days

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Summary Of Recommendations

• Offer continued supportive care
• Offer compassion understanding
• Offer guidance
• Offer hope

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In Conclusion...

• Prevention is the best approach!
• Dont recap needles!
• Wash area with soap and water!
• Seek counseling and health care at once!

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MAHALO!