This program is supported by a grant from the New York State Department of Health AIDS Institutes:

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This program is supported by a grant from the New
York State Department of Health AIDS Institutes
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Non-Occupational Post-Exposure Prophylaxis(nPEP)

• Douglas G. Fish, MD
• Head, Division of HIV Medicine
• Albany Medical College
• November 2005

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Objectives

• Definitions
• Risk assessment
• Indications for nPEP
• Treatment and monitoring
• Hepatitis B and C considerations

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Case Scenario

• 33 yr male presents to your ER after a night of
  partying/beer-drinking, whereupon he engaged in
  receptive oral sex with a man he later learned
  was HIV-seropositive. It is now 18 hours
  post-exposure.
• You would
• 1) offer reassurance, since transmission risk is
  low, with standard STD screening risk-reduction
  counseling
• 2) recommend baseline HIV testing, counseling,
  and follow-up without PEP, along with STD
  screening
• 3) recommend PEP with a 3-drug-regimen

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History - NonOccupational PEP

• Occupational PEP 1980s
• NYS sexual assault guidelines 1997
• Massachusetts and Rhode Island have nPEP
  guidelines
• California offers PEP for sexual assault
• CDC MMWR 199847(No. RR-17)1-14.
• New York State www.hivguidelines.org

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Evidence for nPEP Recommendations

• No randomized, placebo-controlled trials
• Best practice evidence
• Expert opinion
• Medical Care Criteria Committee of AIDS Institute

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Evidence for Efficacy of Post-Exposure
Prophylaxis

• Animal data
• CDC case-control study
• Perinatal transmission data
• PACTG 076 with 66 risk reduction with ZDV
• Sperling RS et al. N Engl J Med 19963351621-9.
• NYS observational data showed 9.3 transmission
  rate among infants receiving PEP beginning in the
  first 48 hours of life
• Wade N et al. N Engl J Med 1998339(20)1409-14.

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Animal Studies Observed Outcomes

• Suppression or delay of antigenemia
• Early administration more effective than later
• Larger inocula decrease prophylactic efficacy
• Decreased antiviral doses decrease prophylactic
  efficacy

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Macaques and PMPA (Tenofovir DF)

• Macaques injected with SIV
• 28 day course PMPA protective if initiated at 24
  hours post-exposure
• infections seen if initiation delayed 48-72 hours
  post-exposure
• infections seen if treatment duration shortened
  to 10 days
• no protection if treatment duration shortened to
  3 days

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Macaques and PMPA (Tenofovir)

• Macaques exposed intravaginally to HIV-2
• Protection observed with 28-day course of PMPA
  given 12 and 36 hours after exposure
• Infection observed if PMPA administration delayed
  until 72 hours after exposure

J Virol 199872(5)4265-73 200074(20)9771-5.
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CDC Study Relative Risk for Transmission after
Percutaneous Occupational Exposure

• Risk Factor
• Deep injury
• Visible blood on device
• Terminal illness in patient
• Device in patient blood vessel
• ZDV use by HCW

• Odds Ratio 15.0
  6.2 5.6
  4.3 0.19

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Components of nPEP Evaluation

• HIV risk assessment
• HIV and STD testing and treatment
• Prevention and risk-reduction counseling
• Clinicians able to prescribe antiretroviral
  therapy
• Timely access to care and initiation of PEP

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Assessing Risk

• Consider the following
• Circumstances leading to HIV exposure
• Risk of HIV acquisition based on type of exposure
• Possibility that the source is HIV-infected
• Provide risk-reduction and primary prevention
  counseling
• nPEP not indicated for negligible or low risk of
  HIV infection

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Risk Behavior

• PEP recommended in situations of
• Isolated exposure (sexual, needle, trauma)
• Lapse in previous risk-reduction practices
• When patients express interest in behavioral
  change
• Repeated high-risk behavior or presentation for
  repeat courses of PEP
• Opportunity for intensification of education
  prevention
• Attempt behavioral change

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Risk of Acquisition
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Estimated Transmission Risk
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References for HIV Transmission Risk

• 1) Kaplan EH et al. J Acquir Immune Defic Syndr
  199251116-1118.
• 2) DeGruttola V et al. J Clin Epidemiol
  198942849-856.
• 3) Varghese B et al. Sex Transm Dis
  20022938-43.
• 4) European Study Group. BMJ 1992304809-813.
• 5) Dillon B et al. 7th CROI, San Francisco, CA
  2000 abstract 473.
• 6) Page-Shafer K et al. AIDS 2002162350-2352.

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Community Needlestick Injuries

• Consider
• HIV prevalence in the community or facility
• Surrounding prevalence of injection drug use
• DO NOT TEST discarded needles for HIV
• Consider tetanus vaccination if puncture wound

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Bites

• Estimated 250,000 bites annually in the U.S.
• HIV levels in saliva very low
• Documented transmission has involved blood-tinged
  saliva 1,2
• Consider PEP when
• Blood exposure to biter
• Blood exposure to bitten person (e.g. source has
  bleeding gums or lesions)
• Blood exposure to both parties

1 Vidmar L et al. Lancet 19963471762-1763. 2
Pretty I et al. Am J Forensic Med Pathol
199920232-239.
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Considering HIV Status of Exposure Source

• If HIV-positive source, consider their
• CD4 cell count
• Viral load
• Antiretroviral medication history
• Antiretroviral resistance history
• If anonymous or unknown status source
• Consider potential risk of HIV infection,
  including information on regional prevalence

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Contraindications to nPEP

• Prophylaxis for pregnancy attempts with an
  HIV-infected male partner
• Prophylaxis for persons planning to engage in
  high-risk behavior

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Exposure Work-up

• Recommend baseline HIV testing
• Declination of HIV testing should not preclude
  PEP, if indicated.
• Assess for sexually transmitted infections (STIs)
  and provide prophylaxis in the sexually-exposed
  patient
• To include chlamydia, gonorrhea, syphilis
• Baseline pregnancy testing for women
• Offer emergency contraception

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Behavioral Risk-Reduction Counseling

• Behavioral intervention for risk-reduction should
  occur, regardless of whether PEP is initiated.
• Assess for emotional, psychological, and social
  factors, such as depression, substance use, and
  history of sexual abuse.
• Refer to mental health and/or substance use
  programs, as appropriate.

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Sexual Assault

• Survivors should be treated in an emergency
  department or other healthcare setting where
  appropriate medical resources are readily
  available.
• When deciding about nPEP, assess
• Whether a significant exposure has occurred
• Knowledge of the HIV status of the alleged
  assailant
• Decision to recommend PEP should not be
  influenced by the geographic location of the
  assault.
• Whether the survivor is willing to complete PEP

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Sexual Assault

• Candidates for HIV PEP include survivors exposed
  by direct contact (to semen or blood of the
  alleged assailant) to the
• Vagina
• Anus
• Mouth
• Broken skin
• Mucous membranes
• PEP should be offered in cases of bites resulting
  in visible blood

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Sexual Assault Follow-up

• If survivor too distraught to discuss or decide
  about PEP, offer first dose and follow-up within
  24 hours
• If PEP initiated, follow-up within 24 hours is
  also recommended to review understanding,
  tolerance, adherence, and to ensure subsequent
  follow-up.
• May discontinue PEP if assailant found to be HIV
  negative

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Payment Methods

• Medicaid/Medicare
• Private insurance, if prescription drug plan
• If no coverage, facility can include in annual
  Institutional Cost Report for indigent care
• Crime Victims Board (CVB)
• Documentation of a medical visit for a forensic
  physical exam satisfies CVB reporting requirement
• Will directly reimburse pharmacy
• www.cvb.state.ny.us

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Rape Crisis Counselor

• Should be active participant in the discussion
  regarding HIV PEP
• Follow-up with rape crisis counselor or outreach
  worker who will work with the survivor critical
• May be part of the multidisciplinary team, but if
  not, HIV release necessary to communicate with
  outside counselor

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nPEP Recommendations

• Initiate ideally within 2 hrs, up to 36 hrs
• Discuss and document the following
• 1) potential benefit, unproven efficacy
  potential toxicity of PEP
• 2) importance of adherence
• 3) need to initiate/resume risk reduction
  prevention behaviors
• 4) signs symptoms of primary HIV infection
• 5) need for clinical lab monitoring follow-up

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Slide compliments of Dr. Neal Gregory Chatham,
NY
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Identifying Primary HIV Infection

• Mono-like illness - often with fever, rash,
  myalgias, lymphadenopathy, pharyngitis
• Diagnose with quantitative HIV RNA PCR
• HIV serology will be negative early, but PCR
  positive
• False positive rate of PCR testing is
  approximately 3 and is usually a low copy number
• Repeat ELISA/WB in 4-6 weeks if initial ELISA
  negative and PCR positive.
• Remember PCR testing does not supplant
  ELISA/Western Blot for routine diagnosis of HIV
  infection

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nPEP/PEP Recommendations

• Recommended Antiretroviral Regimen (3 agents)
  for 4 weeks
• Zidovudine (ZDV)
• 300 mg bid
• Lamivudine (3TC)
• 150 mg bid
• Tenofovir (TDF)
• 300 mg daily with food

Co-formulated as combivir
May substitute ZDV for weight-adjusted stavudine
if not tolerated Dose-reduce with renal
insufficiency
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nPEP/PEP Alternative Recommendations

• Substitutions for tenofovir may include
• Nelfinavir 1250 mg bid
• Lopinavir/ritonavir 400/100 mg bid
• If PIs cant be used, an NNRTI may be considered
• Efavirenz in men/women of non-childbearing
  potential
• Nevirapine ONLY when no other options exist
• Dose-escalate nevirapine, if used

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Specific Antiviral Issues in PEP or nPEP

• Pregnancy
• Efavirenz contraindicated due to teratogenicity
  potential
• Amprenavir/fosamprenavir should be avoided in the
  second and third trimesters, as it may induce
  skeletal ossification
• a sulfa drug
• Avoid didanosine/stavudine combination, as it has
  been associated with fatal lactic acidosis in
  pregnant women

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Beyond 36 Hours

• Decisions regarding the initiation of PEP beyond
  36 hours post-exposure should be made by the
  clinician in conjunction with the patient, with
  the realization of diminished potential for
  success when timing of initiation is prolonged.
• Depends on likelihood of HIV transmission

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Tailoring Antiretroviral PEP Regimens

• Treatment history of source patient or resistance
  assays may be helpful in choosing post-exposure
  regimen
• If source patients regimen successful, consider
  similar regimen for nPEP.
• If source patients regimen unsuccessful,
  consider agents source patient has not received,
  for nPEP.

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Tailoring Antiretroviral PEP Regimens -
Counterpoint

• Use of treatment or resistance data in choosing a
  PEP regimen could lead to use of newer agents
  with less available toxicity data
• Source patients failure to respond to antiviral
  regimens may reflect non-adherence rather than
  resistance
• Past resistance testing may not apply to
  circulating isolates
• In perinatal transmission study PACTG-076,
  maternal zidovudine resistance did not preclude a
  protective effect of zidovudine to the infant.

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Monitoring of nPEP/PEP
Recommended even if PEP is declined.
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Longitudinal Care

• Barrier protection for 6 months, while monitoring
  ongoing
• Avoid breastfeeding for 6 months
• Since most HIV is diagnosed within 3 months,
  women preferring to breastfeed between 3-6 months
  should carefully weigh risks/benefits with their
  clinicians

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Rapid Testing

• OraQuick
• Fingerstick
• Results available as soon as 30 minutes
• Needs confirmation with Western Blot if positive
• Informed consenting process the same
• CLIA-waived test
• Unavailability of rapid test result should not
  delay initiation of PEP

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Exposure to Hepatitis B

• HCW unvaccinated
• Source unknown/unavailable HB vaccine series
• Source HBsAg negative Initiate HB vaccine series
• Source HBsAg positive HBIG x 1 (0.06 ml/kg IM)
  and HB vaccine series

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Exposure to Hepatitis B

• Known responder to HBV vaccine
• no treatment regardless of source status
• Known non-responder to HBV vaccine
• no treatment if source HBsAg negative
• if source HBsAg positive or unknown/not
  available
• HBIG x 1 and revaccinate HB series (preferred if
  have not completed a second 3-dose series) OR
• HBIG x 2, one month apart (preferred if failed a
  second complete series)

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Exposure to Hepatitis B

• Ab response unknown post-vaccination
• Test exposed person for anti-HBs
• If inadequate Ab response (lt10mIU/ml anti-HBS)
  and source HBsAg positive
• HBIG x 1, and vaccine booster
• If inadequate Ab response and source unknown/not
  available
• initiate revaccination

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Exposure to Hepatitis C
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Exposure to Hepatitis C

• Immunoglobulin or antivirals not recommended for
  PEP after exposure to HCV-positive blood
• Limited but growing data that early antiviral
  therapy for HCV may be beneficial, if exposed
  person contracts acute HCV
• NEJM early release 10/1/2001www.nejm.org
• Jaeckel E et al. N Engl J Med 20013451452-7
• Refer to specialist knowledgeable in this area

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San Francisco nPEP Study

• Purpose to study the feasibility of PEP after
  sexual or IDU exposure to HIV
• Eligibility potential sexual or IDU exposure to
  HIV within previous 72 hours
• Timeframe December 1997 through March 1999
• Results (401 participants)
• Most of participants white, college-educated,
  employed men
• 93.5 sexual exposure 86 of those were MSM
• 43 definite HIV infection in source partner

Kahn JO et al. Jour Inf Dis 2001183(5)707-14.
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San Francisco nPEP Study

• 397 participants treated
• 78 completed 4 weeks of treatment (zidovudine/
  lamivudine standard)
• Subjective toxicities common biochemical
  toxicities uncommon
• Median time from exposure to treatment 33 hours
• 75 available for 6 month follow-up HIV testing -
  all seronegative
• Majority of exposures from a lapse in safe sex
  practices rather than habitual high-risk
  behavior
• By 6 months after initial exposure, 39 had
  requested a second course of PEP

Kahn JO et al. Jour Inf Dis 2001183(5)707-14.
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Summary

• PEP is effective, but not a guarantee
• Want a low-toxicity, easy-to-adhere regimen,
  hence the change in NYS PEP guidelines
• PEP regimens the same, whether for occupational
  or sexual assault prophylaxis
• Rapid testing likely to revolutionize how we
  utilize PEP/nPEP

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Special Thanks

• Medical Care Criteria Committee
• Rona Vail, MD
• Amneris Luque, MD, Chair
• Peter Piliero, MD, Past Chair
• Lou Smith, MD - Bureau of Epidemiology, NY State
  Department of Health, for use of some of her
  slides

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For more HIV-related resources, please visit
www.hivguidelines.org