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Recommendations for Postexposure Prophylaxis with Occupational Exposure to HIV David H. Spach, MD Medical Director, Northwest AIDS Education and Training Center Associate Professor of Medicine,Division of Infectious Diseases University of Washington, Seattle. DHS/Occupational/PP.
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Recommendations for Postexposure Prophylaxis with Occupational Exposure to HIVDavid H. Spach, MDMedical Director, Northwest AIDS Education and Training CenterAssociate Professor of Medicine,Division of Infectious DiseasesUniversity of Washington, Seattle DHS/Occupational/PP
Occupational Blood-borne ExposuresRelative Risk of Seroconversion with Percutanous Injury . From: CDC. MMWR 2001;50 (RR11):1-42. DHS/Occupational Exposure/PP
HIV: OCCUPATIONAL PEP DHS/HIV/Pathogenesis/PP
A 26-year-old medical student sticks himself in the palm of his hand during a code of an HIV-infected patient (in the emergency room). The source patient’s most recent CD4 count was 26 cells/mm3 and HIV RNA 82,000 (not on antiretroviral therapy). The source patient is HBsAg-negative and HCV-negative. a) What PEP would you recommend? b) How long would you continue the PEP? DHS/Occupational Exposure/PP From
HIV: Documented SeroconversionsThrough June 2000 • 49: Blood • 1: Visible bloody body fluid • 3: Unspecified fluid • 3: Concentrated virus in laboratory N = 56 From: CDC. MMWR Surv. Report 2000;11:No. 2. DHS/Occupational /PP
HIV: HCW Documented Seroconversions N = 50 Percutaneous Mucocutaneous DHS/Occupational /PP From: CDC. MMWR 1998;47:No. RR-7.
HIV: Seroconversion in Health Care Workers • Primary HIV Infection - Experienced in 81% of HCWs - Occurred median 25 days after exposure • Seroconversion - Exposure to seroconversion median 46 days - Seroconversion by 6 months in 95% of HCWs - 3 persons with seroconversion at 6-12 months DHS/Occupational/PP From: CDC. MMWR 1998;47:No. RR-7. From
Risk Factors for HIV Seroconversion in HCWs Risk Factor Adjusted Odds Ratio* Deep Injury 15.0 Visible Blood on Device 6.2 Terminal Illness in Source Patient 5.6 Needle in Source Vein/Artery 4.3 PEP with Zidovudine (AZT) 0.2 *All Risk Factors were significant (P < 0.01) From: NEJM 1997;337:1485-90. DHS/Occupational /PP
HIV: Antiretroviral Therapy Nucleoside Analogues HIV RNA DNA Nucleus Host Cell Non-Nucleosides Protease Inhibitors FrAdapted from: Walker B. IDSA 1998
HIV PEP: Percutaneous Exposure Source Infection Status Exposure Type HIV+ Class 1 HIV+ Class 2 Less Severe More Severe Basic (2 Drugs) Expanded (3 Drugs) Expanded (3 Drugs) Expanded (3 Drugs) Less Severe: eg. solid needle, superficial injuryMore Severe: eg. Large-bore hollow needle, deep puncture, visible blood on device, or needle used in patient’s artery or veinClass 1: Asymptomatic or low HIV RNA (<1500)Class 2: Symptomatic or known high HIV RNA From: CDC. MMWR 2001;50 (RR11):1-42. DHS/PEP Rx/PP
HIV PEP: Percutaneous Exposure Source Infection Status Exposure Type HIV+ Class 1 HIV+ Class 2 Less Severe More Severe Basic (2 Drugs) Expanded (3 Drugs) Expanded (3 Drugs) Expanded (3 Drugs) Less Severe: eg. solid needle, superficial injuryMore Severe: eg. Large-bore hollow needle, deep puncture, visible blood on device, or needle used in patient’s artery or veinClass 1: Asymptomatic or low HIV RNA (<1500)Class 2: Symptomatic or known high HIV RNA From: MMWR 2001;50 (RR-11):1-42. DHS/PEP Rx/PP
HIV PEP: Mucous Membrane Exposure Source Infection Status Exposure Type HIV+ Class 1 HIV+ Class 2 Small Volume Large Volume Consider Recommend Basic (2 Drugs) Basic (2 Drugs) Recommend Recommend Basic (2 Drugs) Expanded (3 Drugs) Class 1: Asymptomatic or low HIV RNA (<1500)Class 2: Symptomatic or known high HIV RNA From: MMWR 2001;50 (RR-11):1-42. DHS/PEP Rx/PP
HIV PEP: Mucous Membrane Exposure Source Infection Status Exposure Type HIV+ Class 1 HIV+ Class 2 Small Volume Large Volume Consider Recommend Basic (2 Drugs) Basic (2 Drugs) Recommend Recommend Basic (2 Drugs) Expanded (3 Drugs) Class 1: Asymptomatic or low HIV RNA (<1500)Class 2: Symptomatic or known high HIV RNA From: MMWR 2001;50 (RR-11):1-42. DHS/PEP Rx/PP
HIV Postexposure ProphylaxisSource Unknown or Status of Source Unknown • Source of Unknown HIV Status- Generally, no PEP warranted; however consider basic 2-drug PEP for sources with HIV risk factors. • Unknown Source- Generally, no PEP warranted; however consider basic 2-drug PEP in settings where exposure to HIV-infected persons is likely. From From: MMWR 2001;50 (RR-11):1-42. DHS/Occupational Exposure/PP
HIV PEP Rx: Basic Regimen Basic Regimen Dose Zidovudine (ZDV, AZT) + Lamivudine (3TC) 300 mg bid or 200 mg tid 150 mg bid Dose Alternate Basic Regimen Didanosine (ddI) + Stavudine (d4T) 400 mg qd (250 mg qd if < 60 kg) 40 mg bid (30 mg bid if <60 kg) Stavudine (d4T) + Lamivudine (3TC) 200 mg bid (125 mg bid if < 60 kg) 150 mg bid From: MMWR 2001;50 (RR-11):1-42. DHS/PEP Rx/PP
HIV PEP Rx: Expanded Regimen Expanded Regimen Basic Regimen + One of Following Dose Medication Indinavir (IDV) Nelfinavir (NFV) Efavirenz (EFV) Abacavir (ABC) 800 mg q8h 750 mg tid or 1250 mg bid 600 mg qd 300 mg bid From: MMWR 2001;50 (RR-11):1-42. DHS/PEP Rx/PP
Tenofovir (PMPA) for HIV-2 PEP in Macaques Study Design Results (% Infected) • Methods • - HIV-2 inoculated intravaginally • - N = 16 female macaques • Regimens • - Control vs. Tenofovir regimens • - PEP started @ 12, 36, or 72 h • - PEP Rx for 28d From: Otten RA et al. J Virol 2000;74:9771-5. DHS/Occupational/HIV
Tenofovir (PMPA) for SIV PEP in Macaques Study Design Results for PEP Started @ 24h • Methods • - SIV inoculated IV • - N = 24 macaques • Regimens • - Control vs. Tenofovir regimens • - PEP started @ 24, 48, or 72 h • - PEP Rx for 3, 10, or 28d From: Tsai CC et al. J Virol 1998;72:4265-73. DHS/Occupational/HIV
CTL Responses to HIV Exposure in HCWs CTL Response Situation HCW exposed to HIV+ source -Took AZT PEP -Did not take PEP HCW exposed to HIV-source 7/20 (35%) 1/7 (14%) 6/13 (46%) 0/20 (0%) D’Amico R, et al. Infect Control Hosp Epi 1999;20:428-30. DHS/PEP Rx/PP
Failure of Combination HIV PEP Rx Regimen Source on ARV Meds ZDV + ddI ZDV + ddI *3 Drugs ZDV + ddI + 3TC + IDV ddI + d4T + NVP Yes No Yes (not resistant) Yes (resistant) Yes (resistant) *ZDV + 3TC + IDV x 48h, then d4T + 3TC + IDV From: MMWR 2001;50 (RR-11):1-42. DHS/PEP Rx/PP
“From a theoretical perspective, risk stratification is sensible; however, from a practical perspective, these issues are often murky. For individuals who believe they have experienced an occupational HIV exposure, offering less than the presumably most effective regimen may seem objectionable. Thus, in our institution (NIH), we tend to offer the 3-drug regimen, including a protease inhibitor....” - DK Henderson- From: JAMA 1999;281:931-6. DHS/Occupational Exposure/PP From
Tolerability of HIV PEP in HCWs From: Parkin JM. Lancet 2000;355:722-3. DHS/Occupational HIV /PP
Tolerability of HIV PEP in HCWs From: Wang SA. Infect Control Hosp Epidemiol 2000;231:780-5. DHS/Occupational HIV /PP
HIV Postexposure ProphylaxisSerious Adverse Events Associated with Nevirapine N = 22 Serious Adverse Events - Hepatotoxicity = 12 (2 with liver failure) - Skin Reaction = 14 From: CDC. MMWR 2001;49 (51);1153-6. DHS/HIV/AIDS /PP
Occupational HIV Exposure: PEP Follow-Up • HIV Antibody Testing: Baseline, 6w, 12w, 6m, +/- 12m • Routine use of HIV RNA: not recommended • Drug Toxicity Monitoring: baseline and at 2 weeks • Sexual abstinence or condom use (especially in first 6-12 weeks after exposure) • Avoid Pregnancy DHS/Occupational /PP From: CDC. MMWR 2001;50 (RR11):1-42.
A 39-year-old nurse sticks herself in the finger with a needle used to draw blood from an HIV-infected patient. The source patient’s most recent CD4 count was 135 cells/mm3 and HIV RNA 26,400; the source patient is on AZT + 3TC + Indinavir and is about to go on a new regimen. a) What PEP regimen would you recommend? DHS/Occupational Exposure/PP From
“If the source-person’s virus is known or suspected to be resistant to one or more of the drugs included in the PEP regimen, the selection of drugs to which the source patient’s virus is unlikely to be resistant is recommended.” - Centers for Disease Control and Prevention- From: CDC. MMWR 1998;47:No. RR-7. DHS/Occupational Exposure/PP From
HIV: PEP Resources • Clinician’s PEP Hotline 888-448-4911 • Reporting to CDC 404-893-0485 DHS/Occupational /PP