Guideline Summary Updated US Public Health Service Guidelines for the Management of Occupational Exposures to HIV and Recommendations for Postexposure Prophylaxis Published August 2013 AETC NRC Slide Set

August 2013www.aidsetc.org These slides were developed using the September 2013 updated guidelines on postexposure prophylaxis (PEP) following occupational exposure to HIV. The intended audience is clinicians involved in the care of health care personnel (HCP) with occupational exposure to HIV. Users are cautioned that, because of the rapidly changing field of HIV care, this information could become out of date quickly. Finally, it is intended that these slides be used as prepared, without changes in either content or attribution. Users are asked to honor this intent. – AETC NRC About This Presentation 2

August 2013www.aidsetc.org Updated Guidelines for the Management of Occupational Exposures to HIV and Recommendations for Postexposure Prophylaxis Developed by the Public Health Service Interagency Working Group, convened by the CDC 3

August 2013www.aidsetc.org Guidelines Outline  Principal changes from previous PEP guidelines  Health care personnel and exposure  Risk of occupational transmission of HIV  ARV toxicities and interactions  Selection of HIV PEP regimens  Resistance to ARVs  ARV drugs during pregnancy and lactation  Management by emergency physicians 4

August 2013www.aidsetc.org Guidelines Outline (2)  Recommendations for the management of HCP potentially exposed to HIV  HIV PEP  Source patient testing  Timing and duration of PEP  Selection of PEP drugs  Follow-up of exposed HCP  Postexposure testing  Monitoring and management of PEP toxicity 5

August 2013www.aidsetc.org What the Guidelines Emphasize  Prompt management of occupational exposures  Selection of effective and tolerable PEP regimens  Potential toxicities and interactions of PEP drugs  Consultation with experts for postexposure management strategies  Counseling and follow-up of exposed personnel 6

August 2013www.aidsetc.org Principal Changes from Previous PEP Guidelines  Elimination of risk stratification for exposure incidents  3-drug (or more) PEP regimen for all  Expanded list of ARVs for PEP  Emphasis on tolerability and convenience of PEP regimen  New recommendations for follow-up HIV testing 7

August 2013www.aidsetc.org Health Care Personnel: Definition  HCP: all paid and unpaid persons working in healthcare setting who have the potential for exposure to infectious materials 8

August 2013www.aidsetc.org Occupational Risk Exposures in HCP  Percutaneous injury (needlestick, cut) OR  Contact of mucous membrane or nonintact skin WITH: Blood Tissue Other body fluids that are potentially infectious (cerebrospinal, synovial, pleural, pericardial, peritoneal, or amniotic fluids; semen or vaginal secretions) 9

August 2013www.aidsetc.org NOT Considered Infectious for HIV Unless Visibly Bloody  Feces  Nasal Secretions  Saliva  Sputum  Sweat  Tears  Urine  Vomitus 10

August 2013www.aidsetc.org Risk of Occupational Transmission of HIV  Following percutaneous exposure: approximately 0.3%  Following mucous membrane exposure: approximately 0.09%  Risk following nonintact skin exposure estimated to be <0.09%  Risk following exposure to fluids or tissues other than HIV-infected blood estimated to be “considerably lower” than for blood exposure 11

August 2013www.aidsetc.org Factors Associated with Increased Risk  Visible contamination of device (such as needle) with patient’s blood  Needle having been placed directly into vein or artery  Hollow-bore (vs solid) needle  Deep injury  Source patient with terminal illness  High viral load* * Risk of transmission via occupational exposure to a source patient with undetectable viral load is thought to be very low but not impossible; PEP should be offered. 12

August 2013www.aidsetc.org Toxicity of PEP Regimens  PEP should be taken for a full 4 weeks  Substantial proportion of HCP taking earlier ARVs as PEP did not complete full course of PEP  Side effects of ARV drugs are common, and a major reason for not completing PEP regimens  Regimens that are tolerable for short-term use should be selected  Potential side effects should be discussed, and treatment for anticipated side effects should be prescribed preemptively, if indicated 13

August 2013www.aidsetc.org Interactions of ARV Agents  ARVs can have serious interactions with other drugs  Before prescribing PEP, carefully evaluate concomitant medications, including over-the- counters, supplements, and herbals  Consult package inserts or other resources on ARV drug-drug interactions; consult with experts  Avoid interacting drugs and monitor carefully, as appropriate 14

August 2013www.aidsetc.org Selection of HIV PEP Regimens: Rationale for Current Recommendations  Guidelines recommend use of ≥3 ARVs for treatment of HIV infection  Optimal number of ARVs needed for HIV PEP is unknown  Newer ARVs are better tolerated and have better toxicity profiles than agents previously used for PEP  Thus, PEP regimens comprising 3 (or more) tolerable ARVs now recommended for all occupational exposures to HIV 15

August 2013www.aidsetc.org Selection of HIV PEP Regimens: Rationale for Current Recommendations (2)  To encourage HCP to complete the PEP regimen:  Optimize side effect and toxicity profiles  Optimize dosing convenience 16

August 2013www.aidsetc.org Resistance to ARVs  Resistance of the source virus to ARVs, particularly to 1 or more that may be included in a PEP regimen, may reduce PEP efficacy  Occupational transmission of drug-resistant HIV strains, despite PEP, has been reported  If source patient is known or suspected to harbor drug- resistant HIV, consult with experts for PEP selection  Do not delay initiation of PEP; use ARVs to which the source virus is unlikely to be resistant  Resistance testing at time of exposure is not practical, given length of time required for results  If resistance test results become available during PEP, consider possible modification of PEP regimen if indicated 17

August 2013www.aidsetc.org ARVs during Pregnancy and Lactation  Decision to offer PEP based on same considerations as in other HCP  Risk of HIV transmission during pregnancy or breast-feeding is markedly increased in acute HIV infection  Potential risks of ARVs for pregnant women, fetuses, and infants  Expert consultation recommended in all cases 18

August 2013www.aidsetc.org ARVs during Pregnancy and Lactation (2)  Potential toxicities of ARVs during pregnancy and lactation depend on timing and duration of exposure, and on number and type of ARVs  Special considerations during pregnancy  Efavirenz: 1st-trimester exposure may increase risk of CNS defects  Avoid efavirenz during 1st trimester  If efavirenz-based PEP is used, do pregnancy test to rule out early pregnancy; counsel nonpregnant women to avoid pregnancy until after completing PEP  Stavudine + didanosine  Not recommended; increased risk of lactic acidosis 19

August 2013www.aidsetc.org ARVs during Pregnancy and Lactation (3)  Special considerations in breast-feeding  Counsel lactating HIV-exposed HCP to weigh risks and benefits of continued breast-feeding both while taking PEP and while being monitored for HIV seroconversion  Breast-feeding is not a contraindication to PEP, especially given high risk of HIV transmission through breast milk should acute HIV infection occur  3-drug ARV regimens given to HIV-infected breast- feeding women has been shown to decrease risk of transmission to their infants  Consider stopping breast-feeding to eliminate risk of HIV transmission 20

August 2013www.aidsetc.org Management of Occupational Exposure by Emergency Physicians  Institutions are recommended to develop clear protocols for management of occupational exposures, indicating:  Formal expert consultation mechanism (eg, in-house ID consultant or PEPline)  Appropriate initial source patient and exposed HCP laboratory testing  Procedures for counseling exposed HCP  Identifying and having an initial HIV PEP regimen available  Mechanism for outpatient HCP follow-up 21

August 2013www.aidsetc.org Management of HCP Potentially Exposed to HIV  Recommendations reflect expert opinion; limited data on safety, tolerability, efficacy, and toxicity of PEP  Consider potential benefits and risks of PEP (including possible toxicity and drug interactions)  Consult with experts  Reevaluate exposed HCP within 72 hours after exposure, especially as additional information about the exposure or source person becomes available 22

August 2013www.aidsetc.org Source Patient HIV Testing  If possible, determine the HIV status of exposure source patient to guide appropriate use of PEP  For sources whose HIV status is unknown, rapid HIV testing facilitates decisions about need to initiate or continue PEP  Investigation of whether a source patient might be in the window period before HIV seroconversion is not necessary, unless acute retroviral syndrome is suspected  4th-generation HIV Ag/Ab tests allow identification of most HIV infections during the window period 23

August 2013www.aidsetc.org Source Patient HIV Testing (2)  PEP initiation should not be delayed while waiting for HIV test results  If the source is found to be HIV negative, PEP should be discontinued, and no follow-up HIV testing for HCP is needed 24

August 2013www.aidsetc.org Timing and Duration of PEP  PEP is most effective when begun soon after the exposure, less effective as time increases (animal studies)  PEP should be started as soon as possible after the exposure, preferably within hours  Point at which no benefit may be gained is not defined; in animal studies less effective if started >72 hours after exposure  Optimal duration unknown; 4 weeks appeared protective in occupational and animal studies  PEP should be taken for 4 weeks, if tolerated 25

August 2013www.aidsetc.org Selection of HIV PEP Drugs  Stratifying severity of exposure to determine the number of PEP drugs to be given is no longer recommended  PEP regimen of 3 (or more) ARVs is recommended for all occupational HIV exposures  Typically, 2-NRTI backbone + integrase inhibitor, ritonavir-boosted protease inhibitor, or NNRTI  Other ARV classes may be indicated (eg, if resistant virus), but consult with experts 26

August 2013www.aidsetc.org Selection of HIV PEP Drugs (2)  No definitive data show increased efficacy of 3- drug vs 2-drug PEP regimens; current recommendation based on:  Superior efficacy of 3 ARVs in reducing HIV RNA in HIV-infected persons  Concerns about source patient drug resistance to ARVs  Safety and tolerability of newer ARVs  Potential for improved PEP adherence with newer ARVs 27

August 2013www.aidsetc.org Selection of HIV PEP Drugs (3)  Choose ARVs with favorable side effect profile and convenient dosing schedule, to facilitate adherence and completion of 4 weeks of PEP  PEP not justified for exposures that pose negligible risk of HIV transmission  Reevaluate and modify PEP regimen whenever additional information about the source is obtained (eg, treatment history or ARV resistance)  Consultation with experts is recommended, but should not delay PEP initiation 28

August 2013www.aidsetc.org PEP Regimens  Preferred HIV PEP regimen:  Raltegravir 400 mg BID + TDF/FTC (Truvada) 1 QD 29

August 2013www.aidsetc.org PEP Regimens (2)  Alternative regimens (combine 1 drug or drug pair from left column with 1 NRTI pair from right column) : Raltegravir Darunavir + ritonavir Etravirine + Rilpivirine Atazanavir + ritonavir Lopinavir/ritonavir Tenofovir + emtricitabine Tenofovir + lamivudine Zidovudine + lamivudine Zidovudine + emtricitabine Elvitegravir/cobicistat/tenofovir/emtricitabine (Stribild) 30

August 2013www.aidsetc.org PEP Regimens (3)  Alternative ARV agents for use as PEP (only with expert consultation):  Abacavir¹  Efavirenz²  Enfuvirtide  Fosamprenavir  Maraviroc  Saquinavir  Stavudine 1 Use only with expert consultation, and in persons tested negative for HLA B Avoid during first trimester of pregnancy 31

August 2013www.aidsetc.org PEP Regimens (4)  ARV agents generally not recommended for PEP:  Didanosine  Nelfinavir  Tipranavir  ARV agents contraindicated as PEP:  Nevirapine 32

August 2013www.aidsetc.org Selection of Drugs for PEP: Consultation Is Part of the Guidelines “Regular consultation with experts in antiretroviral therapy and HIV transmission is strongly recommended.” 33

August 2013www.aidsetc.org Resources for Consultation  Local experts (eg, HIV or ID consultant, hospital epidemiologist)  National HIV/AIDS Clinicians’ Postexposure Prophylaxis Hotline (PEPline)  24-hour telephone consultation service:

August 2013www.aidsetc.org Situations in Which Expert Consultation Is Advised  Delayed exposure report (ie, >72 hours)  Interval after which benefit from PEP undefined  Unknown source (eg, needle in sharps disposal container or laundry)  Use of PEP to be decided on case-by-case basis  Consider severity of exposure and epidemiologic likelihood of HIV exposure  Do not test needles or other sharp instruments for HIV  Known or suspected pregnancy in the exposed person  Provision of PEP should not be delayed while awaiting consultation 35

August 2013www.aidsetc.org Situations in Which Expert Consultation Is Advised (2)  Breast-feeding in the exposed person  Provision of PEP should not be delayed while awaiting consultation  Known or suspected resistance of the source virus to ARVs  If source person’s virus is known or suspected to be resistant to ≥1 of the drugs considered for PEP, selection of drugs to which the source person’s virus is unlikely to be resistant is recommended  Initiation of PEP should not be delayed while awaiting any results of resistance testing 36

August 2013www.aidsetc.org Situations in Which Expert Consultation Is Advised (3)  Toxicity of the initial PEP regimen  Symptoms (eg, GI symptoms) often manageable without changing PEP regimen by prescribing antiemetic or antimotility agents  Counseling and support for management of side effects is very important  Serious medical illness in the exposed person  Significant illness (eg, renal disease) or coadministration of multiple medications may increase risk of drug toxicity and drug-drug interactions 37

August 2013www.aidsetc.org Follow-Up of Exposed HCP All exposed HCP should receive the following, regardless of whether they receive PEP:  Counseling  Early reevaluation after exposure  Follow-up testing and appointments 38

August 2013www.aidsetc.org Follow-Up of Exposed HCP (2)  Postexposure counseling  Exposed HCP should be advised to use precautions (eg, use latex barriers during sex; avoid blood or tissue donations, pregnancy, and, if possible, breast-feeding) to prevent secondary transmission, especially during the first 6-12 weeks postexposure  For PEP recipients, provide information on :  Need for adherence to PEP, importance of completing PEP regimen  Possible drug toxicities  Possible drug interactions  Symptoms to report to health care provider 39

August 2013www.aidsetc.org Follow-Up of Exposed HCP (3)  Postexposure counseling (cont’d)  Psychological impact of occupational exposure to HIV may be substantial; psychological counseling should be an essential component of the management and care of exposed HCP 40

August 2013www.aidsetc.org Follow-Up of Exposed HCP (4)  Early reevaluation after exposure  Reevaluate exposed HCP within 72 hours after exposure, regardless of whether on PEP  Gives additional opportunity for evaluation, counseling, to reinforced adherence, identify and manage early side effects, improve likelihood of follow-up serologic testing, etc. 41

August 2013www.aidsetc.org Follow-Up of Exposed HCP (5)  Follow-up testing  HIV testing at baseline, 6 weeks, 12 weeks, and 6 months after exposure  If 4th-generation p24 Ag/HIV Ab test is used: HIV testing at baseline, 6 weeks, 12 weeks, and 4 months after exposure  HIV testing for any exposed HCP with symptoms compatible with acute retroviral syndrome, regardless of interval since exposure  If HIV infection is identified, refer for HIV care  Report case to state health department and to CDC COPHI coordinator ( ) 42

August 2013www.aidsetc.org Follow-Up of Exposed HCP (6) Monitoring and management of PEP toxicity:  Evaluation and laboratory testing at baseline and 2 weeks after starting PEP; additionally if symptoms develop  Laboratory tests: CBC, renal and hepatic function tests  Other tests depending on specific toxicities of the drugs in the PEP regimen and on the medical conditions of the HCP  Advise HCP of symptoms that require urgent evaluation (eg, rash, fever, abdominal pain, icterus)  If toxicity noted, consult with expert; consider modification of PEP regimen 43

August 2013www.aidsetc.org Other Occupational and Nonoccupational Exposures  Managing exposure to hepatitis B and C (see previous guideline: CDC. MMWR 2001;50(RR-11); online at  Nonoccupational HIV exposure (see separate guideline: CDC. MMWR 2005;54(RR-9); online at 409a1.htm 409a1.htm 44

August 2013www.aidsetc.org  This presentation was prepared by Susa Coffey, MD, for the AETC National Resource Center in August 2013  See the most current version of this presentation on the AETC NRC website: or on AIDSinfo: About This Slide Set 45