Transcript Non-Occupational Post-Exposure Prophylaxis (nPEP)

This program is supported by a
grant from the New York State
Department of Health AIDS
Institute’s:
Non-Occupational PostExposure Prophylaxis
(nPEP)
Douglas G. Fish, MD
Head, Division of HIV Medicine
Albany Medical College
November 2005
Objectives

Definitions
 Risk assessment
 Indications for nPEP
 Treatment and monitoring
 Hepatitis B and C considerations
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 postexposure.
 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
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 1998;47(No. RR-17)1-14.
 New York State: www.hivguidelines.org

Evidence for nPEP
Recommendations

No randomized, placebo-controlled trials
 Best practice evidence
 Expert opinion
– Medical Care Criteria Committee of AIDS
Institute
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 1996;335:1621-9.
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 1998;339(20):1409-14.
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
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 4872 hours post-exposure
 infections seen if treatment duration
shortened to 10 days
 no protection if treatment duration
shortened to 3 days
J Virol 1998;72(5):4265-73 and
2000;74(20):9771-5
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 1998;72(5)4265-73 & 2000;74(20)9771-5.
CDC Study: Relative Risk for
Transmission after Percutaneous
Occupational Exposure
 Risk Factor
 Odds Ratio
– Deep injury
15.0
– Visible blood on device
6.2
– Terminal illness in patient
5.6
4.3
– Device in patient blood vessel
0.19
– ZDV use by HCW
NEJM 1997;337:1485-1490
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
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
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
Risk of Acquisition
PEP recommended, if source
HIV + or at risk of HIV
*Unprotected receptive &
insertive vaginal or anal
intercourse
*Unprotected receptive
penile-oral contact with
ejaculation
*Oral-vaginal contact with
blood exposure
*Needle-sharing
*Injury with blood exposure
- needlestick, bite, accident
PEP NOT recommended
*Kissing, or oral-oral contact & no
mucosal damage
*Bites without blood
*Needles/sharps exposure not in
contact with HIV + or at-risk
person
*Mutual masturbation – intact skin
*Oral-anal contact
*Receptive penile-oral contact
without ejaculation
*Insertive penile-oral contact
*Oral-vaginal – no blood exposure
Estimated Transmission Risk
Exposure Type if Source
HIV-infected
Needle-sharing exposure
Estimated Risk
Receptive anal intercourse
0.5% (1/200) to 3% (6/200)2,3
Receptive vaginal
intercourse
Insertive anal intercourse
0.1% (1/1000)3,4
0.67% (1/150)1
0.065% (1/1500)3,4
Insertive vaginal intercourse 0.05% (1/2000)3,4
Oral sex with ejaculation
Conflicting data, but felt to be
low-risk. PEP recommended
for performer of oral sex who
5,6
References for HIV
Transmission Risk






1) Kaplan EH et al. J Acquir Immune Defic Syndr
1992;5:1116-1118.
2) DeGruttola V et al. J Clin Epidemiol
1989;42:849-856.
3) Varghese B et al. Sex Transm Dis 2002;29:3843.
4) European Study Group. BMJ 1992;304:809813.
5) Dillon B et al. 7th CROI, San Francisco, CA
2000; abstract 473.
6) Page-Shafer K et al. AIDS 2002;16:2350-2352.
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
Bites

Estimated 250,000 bites annually in the U.S.
 HIV levels in saliva very low
 Documented transmission has involved bloodtinged 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 1996;347:1762-1763.
2 Pretty I et al. Am J Forensic Med Pathol 1999;20:232-239.
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
Contraindications to nPEP

Prophylaxis for pregnancy attempts with an
HIV-infected male partner
 Prophylaxis for persons planning to engage
in high-risk behavior
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
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.
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
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
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
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 Victim’s 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
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
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
Slide compliments of Dr. Neal Gregory
Chatham, NY
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
nPEP/PEP Recommendations

Recommended Antiretroviral Regimen (3
agents) for 4 weeks:
– Zidovudine (ZDV)#
 300 mg bid
Co-formulated as combivir
– Lamivudine (3TC)*
 150 mg bid
– Tenofovir (TDF)*
 300 mg daily with food
#May substitute ZDV for weight-adjusted stavudine if not tolerated
*Dose-reduce with renal insufficiency
nPEP/PEP Alternative
Recommendations

Substitutions for tenofovir may include:
– Nelfinavir 1250 mg bid
– Lopinavir/ritonavir 400/100 mg bid

If PIs can’t 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
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
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
Tailoring Antiretroviral PEP
Regimens

Treatment history of source patient or
resistance assays may be helpful in
choosing post-exposure regimen
– If source patient’s regimen successful,
consider similar regimen for nPEP.
– If source patient’s regimen unsuccessful,
consider agents source patient has not
received, for nPEP.
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 patient’s 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.
Monitoring of nPEP/PEP
Clinic
Visit
Baseline
X
Week 1
X
Week 2
X
Week 3
X
Week 4
X
CBC & LFTs
Diff.
X
X
X
X
X
X
HIV
Ab*
X
X
Month 3
X
Month 6
X
*Recommended even if PEP is declined.
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
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
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
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)
Exposure to Hepatitis B

Ab response unknown post-vaccination
– Test exposed person for anti-HBs
– If inadequate Ab response (<10mIU/ml
anti-HBS) and source HBsAg positive:

HBIG x 1, and vaccine booster
– If inadequate Ab response and source
unknown/not available:

initiate revaccination
Exposure to Hepatitis C
HCV Ab
Baseline
(source
HCV + or
unknown)
4 weeks
4-6 mos
Increase in
ALT in 1st
24 wks
X
ALT
Qualitative
HCV RNA
PCR
X
If source
HCV +
X
X
X
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 10/1/2001:www.nejm.org
– Jaeckel E et al. N Engl J Med 2001;345:1452-7
– Refer to specialist knowledgeable in this area
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 2001;183(5):707-14.
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 2001;183(5):707-14.
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
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
For more HIV-related resources,
please visit www.hivguidelines.org