1 / 51

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 Post-Exposure Prophylaxis (nPEP). Douglas G. Fish, MD Head, Division of HIV Medicine Albany Medical College November 2005. Objectives. Definitions Risk assessment

oke
Download Presentation

Non-Occupational Post-Exposure Prophylaxis (nPEP)

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. This program is supported by a grant from the New York State Department of Health AIDS Institute’s:

  2. Non-Occupational Post-Exposure Prophylaxis(nPEP) Douglas G. Fish, MD Head, Division of HIV Medicine Albany Medical College November 2005

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

  4. 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

  5. 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

  6. Evidence for nPEP Recommendations • No randomized, placebo-controlled trials • Best practice evidence • Expert opinion • Medical Care Criteria Committee of AIDS Institute

  7. 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.

  8. 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

  9. 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 J Virol 1998;72(5):4265-73 and 2000;74(20):9771-5

  10. 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.

  11. 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 CDC Study: Relative Risk for Transmission after Percutaneous Occupational Exposure NEJM 1997;337:1485-1490

  12. 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

  13. 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

  14. 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

  15. Risk of Acquisition

  16. Estimated Transmission Risk

  17. 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;29:38-43. • 4) European Study Group. BMJ 1992;304:809-813. • 5) Dillon B et al. 7th CROI, San Francisco, CA 2000; abstract 473. • 6) Page-Shafer K et al. AIDS 2002;16:2350-2352.

  18. 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

  19. 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 1996;347:1762-1763. 2 Pretty I et al. Am J Forensic Med Pathol 1999;20:232-239.

  20. 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

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

  22. 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

  23. 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.

  24. 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

  25. 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

  26. 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

  27. 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

  28. 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

  29. 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

  30. Slide compliments of Dr. Neal Gregory Chatham, NY

  31. 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

  32. 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

  33. 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 ofnon-childbearing potential • Nevirapine ONLY when no other options exist • Dose-escalate nevirapine, if used

  34. 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

  35. 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

  36. 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.

  37. 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.

  38. Monitoring of nPEP/PEP *Recommended even if PEP is declined.

  39. 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

  40. 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

  41. 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

  42. 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)

  43. 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

  44. Exposure to Hepatitis C

  45. 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

  46. 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.

  47. 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.

  48. 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

  49. 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

More Related