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    1. HIV Post Exposure Prophylaxis for Occupational Exposure and HIV Pre Exposure Prophylaxis

    3. Guideline Summary Updated US Public Health Service Guidelines for the Management of Occupational Exposures to HIV and Recommendations for Postexposure Prophylaxis Published October 2005 AETC NRC Slide Set

    4. December 2007 AETC National Resource Center, www.aidsetc.org Websites to Access the Guidelines http://www.aidsetc.org http://aidsinfo.nih.gov

    5. December 2007 AETC National Resource Center, www.aidsetc.org Occupational Risk Exposures in Health Care Personnel 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) An exposure that might place HCP at risk for HIV infection is defined as a percutaneous injury (e.g., a needlestick or cut with a sharp object) or contact of mucous membrane or nonintact skin (e.g., exposed skin that is chapped, abraded, or afflicted with dermatitis) with blood, tissue, or other body fluids that are potentially infectious. In addition to blood and visibly bloody body fluids, semen and vaginal secretions also are considered potentially infectious. Although semen and vaginal secretions have been implicated in the sexual transmission of HIV, they have not been implicated in occupational transmission from patients to HCP. The following fluids also are considered potentially infectious: cerebrospinal fluid, synovial fluid, pleural fluid, peritoneal fluid, pericardial fluid, and amniotic fluid. The risk for transmission of HIV infection from these fluids is unknown; the potential risk to HCP from occupational exposures has not been assessed by epidemiologic studies in health-care settings. Feces, nasal secretions, saliva, sputum, sweat, tears, urine, and vomitus are not considered potentially infectious unless they are visibly bloody; the risk for transmission of HIV infection from these fluids and materials is low (7). Any direct contact (i.e., contact without barrier protection) to concentrated virus in a research laboratory or production facility requires clinical evaluation. For human bites, clinical evaluation must include the possibility that both the person bitten and the person who inflicted the bite were exposed to bloodborne pathogens. Transmission of HIV infection by this route has been reported rarely, but not after an occupational exposure (812). An exposure that might place HCP at risk for HIV infection is defined as a percutaneous injury (e.g., a needlestick or cut with a sharp object) or contact of mucous membrane or nonintact skin (e.g., exposed skin that is chapped, abraded, or afflicted with dermatitis) with blood, tissue, or other body fluids that are potentially infectious. In addition to blood and visibly bloody body fluids, semen and vaginal secretions also are considered potentially infectious. Although semen and vaginal secretions have been implicated in the sexual transmission of HIV, they have not been implicated in occupational transmission from patients to HCP. The following fluids also are considered potentially infectious: cerebrospinal fluid, synovial fluid, pleural fluid, peritoneal fluid, pericardial fluid, and amniotic fluid. The risk for transmission of HIV infection from these fluids is unknown; the potential risk to HCP from occupational exposures has not been assessed by epidemiologic studies in health-care settings. Feces, nasal secretions, saliva, sputum, sweat, tears, urine, and vomitus are not considered potentially infectious unless they are visibly bloody; the risk for transmission of HIV infection from these fluids and materials is low (7). Any direct contact (i.e., contact without barrier protection) to concentrated virus in a research laboratory or production facility requires clinical evaluation. For human bites, clinical evaluation must include the possibility that both the person bitten and the person who inflicted the bite were exposed to bloodborne pathogens. Transmission of HIV infection by this route has been reported rarely, but not after an occupational exposure (812).

    6. December 2007 AETC National Resource Center, www.aidsetc.org NOT Considered Infectious for HIV, unless Visibly Bloody Feces Nasal Secretions Saliva Sputum Sweat Tears Urine Vomitus

    7. December 2007 AETC National Resource Center, www.aidsetc.org Risk of HIV Infection following Occupational Exposure to HIV-Infected Blood Approximately 0.3% following percutaneous exposure Approximately 0.09% following mucous membrane exposure The risks for occupational transmission of HIV have been described; risks vary with the type and severity of exposure (2,3,7). In prospective studies of HCP, the average risk for HIV transmission after a percutaneous exposure to HIVinfected blood has been estimated to be approximately 0.3% (95% confidence interval [CI] = 0.2%0.5%) (7) and after a mucous membrane exposure, approximately 0.09% (CI = 0.006%0.5%) (3). Although episodes of HIV transmission after nonintact skin exposure have been documented, the average risk for transmission by this route has not been precisely quantified but is estimated to be less than the risk for mucous membrane exposures. The risk for transmission after exposure to fluids or tissues other than HIV-infected blood also has not been quantified but is probably considerably lower than for blood exposures. The risks for occupational transmission of HIV have been described; risks vary with the type and severity of exposure (2,3,7). In prospective studies of HCP, the average risk for HIV transmission after a percutaneous exposure to HIVinfected blood has been estimated to be approximately 0.3% (95% confidence interval [CI] = 0.2%0.5%) (7) and after a mucous membrane exposure, approximately 0.09% (CI = 0.006%0.5%) (3). Although episodes of HIV transmission after nonintact skin exposure have been documented, the average risk for transmission by this route has not been precisely quantified but is estimated to be less than the risk for mucous membrane exposures. The risk for transmission after exposure to fluids or tissues other than HIV-infected blood also has not been quantified but is probably considerably lower than for blood exposures.

    8. December 2007 AETC National Resource Center, www.aidsetc.org Factors Associated with Increased Risk Visible contamination of device (such as needle) with patients 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 (not established in occupational exposure) Epidemiologic and laboratory studies suggest that multiple factors might affect the risk for HIV transmission after an occupational exposure (3). In a retrospective case-control study of HCP who had percutaneous exposure to HIV, increased risk for HIV infection was associated with exposure to a larger quantity of blood from the source person as indicated by 1) a device (e.g., a needle) visibly contaminated with the patients blood, 2) a procedure that involved a needle being placed directly in a vein or artery, or 3) a deep injury. The risk also was increased for exposure to blood from source persons with terminal illness, possibly reflecting either the higher titer of HIV in blood late in the course of acquired immunodeficiency syndrome (AIDS) or other factors (e.g., the presence of syncytia- inducing strains of HIV). A laboratory study that demonstrated that more blood is transferred by deeper injuries and hollow-bore needles lends further support for the observed variation in risk related to blood quantity (3). The use of source-person viral load as a surrogate measure of viral titer for assessing transmission risk has not yet been established. Plasma viral load (e.g., HIV RNA) reflects only the level of cell-free virus in the peripheral blood; latently infected cells might transmit infection in the absence of viremia. Although a lower viral load (e.g., <1,500 RNA copies/ mL) or one that is below the limits of detection probably indicates a lower titer exposure, it does not rule out the possibility of transmission. Epidemiologic and laboratory studies suggest that multiple factors might affect the risk for HIV transmission after an occupational exposure (3). In a retrospective case-control study of HCP who had percutaneous exposure to HIV, increased risk for HIV infection was associated with exposure to a larger quantity of blood from the source person as indicated by 1) a device (e.g., a needle) visibly contaminated with the patients blood, 2) a procedure that involved a needle being placed directly in a vein or artery, or 3) a deep injury. The risk also was increased for exposure to blood from source persons with terminal illness, possibly reflecting either the higher titer of HIV in blood late in the course of acquired immunodeficiency syndrome (AIDS) or other factors (e.g., the presence of syncytia- inducing strains of HIV). A laboratory study that demonstrated that more blood is transferred by deeper injuries and hollow-bore needles lends further support for the observed variation in risk related to blood quantity (3). The use of source-person viral load as a surrogate measure of viral titer for assessing transmission risk has not yet been established. Plasma viral load (e.g., HIV RNA) reflects only the level of cell-free virus in the peripheral blood; latently infected cells might transmit infection in the absence of viremia. Although a lower viral load (e.g., <1,500 RNA copies/ mL) or one that is below the limits of detection probably indicates a lower titer exposure, it does not rule out the possibility of transmission.

    9. December 2007 AETC National Resource Center, www.aidsetc.org Toxicity of PEP Regimens PEP should be given for a full 4 weeks Side effects of ARV drugs are common, and a major reason for not completing PEP regimens Therefore, to the extent possible, regimens that are tolerable for short-term use should be selected Because side effects are frequent and particularly because they are cited as a major reason for not completing PEP regimens as prescribed, the selection of regimens should be heavily influenced toward those that are tolerable for short-term use.Because side effects are frequent and particularly because they are cited as a major reason for not completing PEP regimens as prescribed, the selection of regimens should be heavily influenced toward those that are tolerable for short-term use.

    10. December 2007 AETC National Resource Center, www.aidsetc.org Resistance to ARVs Resistant virus may be present in a treatment-experienced source patient Resistance testing at time of exposure is not practical, because results will not be available to influence choice of initial PEP regimen No data suggest that modifying regimen when resistance test results become available (typically 1-2 weeks) will improve PEP efficacy Expert consultation is recommended Known or suspected resistance of the source virus to antiretroviral agents, particularly those that might be included in a PEP regimen, is a concern for persons making decisions about PEP (36). Drug resistance to all available antiretroviral agents has been reported, and cross-resistance within drug classes is frequent (37). Although occupational transmission of drug-resistant HIV strains has been reported despite PEP with combination drug regimens (36,3840), the effect of exposure to a resistant virus on transmission and transmissibility is not well understood. Since publication of the previous Known or suspected resistance of the source virus to antiretroviral agents, particularly those that might be included in a PEP regimen, is a concern for persons making decisions about PEP (36). Drug resistance to all available antiretroviral agents has been reported, and cross-resistance within drug classes is frequent (37). Although occupational transmission of drug-resistant HIV strains has been reported despite PEP with combination drug regimens (36,3840), the effect of exposure to a resistant virus on transmission and transmissibility is not well understood. Since publication of the previous

    11. December 2007 AETC National Resource Center, www.aidsetc.org Initiating PEP PEP should be started as soon as possible, preferably within hours, rather than days, following exposure When uncertain as to which drugs to choose, start the basic regimen rather than delay PEP should be administered for 4 weeks, if tolerated

    12. December 2007 AETC National Resource Center, www.aidsetc.org Initiating PEP (2) Reevaluate exposed HCP within 72 hours of exposure, especially as additional information about the exposure or source patient becomes available If the source is found to be HIV negative, PEP should be discontinued Rapid HIV testing of the source patient can facilitate decisions regarding PEP when the source patients HIV status is unknown

    13. December 2007 AETC National Resource Center, www.aidsetc.org Selecting the PEP Regimen Selection of number (2 or =3) of drugs is based on assessment of risk for HIV infection Selection of which agents to use is based largely on potential toxicity of PEP drugs and on likelihood of efficacy (especially in the case of resistant virus) Few data on efficacy of individual ARV agents in PEP Determining which agents and how many to use or when to alter a PEP regimen is primarily empiric (34). Guidelines for treating HIV infection, a condition typically involving a high total body burden of HIV, recommend use of three or more drugs (13,14); however, the applicability of these recommendations to PEP is unknown. Among HIV-infected patients, combination regimens with three or more antiretroviral agents have proved superior to monotherapy and dual-therapy regimens in reducing HIV viral load, reducing incidence of opportunistic infections and death, and delaying onset of drug resistance (13,14). In theory, a combination of drugs with activity at different stages in the viral replication cycle (e.g., nucleoside analogues with a PI) might offer an additive preventive effect in PEP, particularly for occupational exposures that pose an increased risk for transmission or for transmission of a resistant virus. Although use of a three- (or more) drug regimen might be justified for exposures that pose an increased risk for transmission, whether the potential added toxicity of a third or fourth drug is justified for lower-risk exposures is uncertain, especially in the absence of data supporting increased efficacy of more drugs in the context of occupational PEP. Offering a two-drug regimen is a viable option, primarily because the benefit of completing a full course of this regimen exceeds the benefit of adding the third agent and risking noncompletion (35). In addition, the total body burden of HIV is substantially lower among exposed HCP than among persons with established HIV infection. For these reasons, the recommendations in this report provide guidance for two- and three- (or more) drug PEP regimens on the basis of the level of risk for HIV transmission represented by the exposure (Tables 1 and 2; Appendix). Determining which agents and how many to use or when to alter a PEP regimen is primarily empiric (34). Guidelines for treating HIV infection, a condition typically involving a high total body burden of HIV, recommend use of three or more drugs (13,14); however, the applicability of these recommendations to PEP is unknown. Among HIV-infected patients, combination regimens with three or more antiretroviral agents have proved superior to monotherapy and dual-therapy regimens in reducing HIV viral load, reducing incidence of opportunistic infections and death, and delaying onset of drug resistance (13,14). In theory, a combination of drugs with activity at different stages in the viral replication cycle (e.g., nucleoside analogues with a PI) might offer an additive preventive effect in PEP, particularly for occupational exposures that pose an increased risk for transmission or for transmission of a resistant virus. Although use of a three- (or more) drug regimen might be justified for exposures that pose an increased risk for transmission, whether the potential added toxicity of a third or fourth drug is justified for lower-risk exposures is uncertain, especially in the absence of data supporting increased efficacy of more drugs in the context of occupational PEP. Offering a two-drug regimen is a viable option, primarily because the benefit of completing a full course of this regimen exceeds the benefit of adding the third agent and risking noncompletion (35). In addition, the total body burden of HIV is substantially lower among exposed HCP than among persons with established HIV infection. For these reasons, the recommendations in this report provide guidance for two- and three- (or more) drug PEP regimens on the basis of the level of risk for HIV transmission represented by the exposure (Tables 1 and 2; Appendix).

    14. December 2007 AETC National Resource Center, www.aidsetc.org How Many Drugs to Use? Assess risk for HIV infection: Type of exposure Less severe: solid needle or superficial injury More severe: large-bore hollow needle, deep puncture, visible blood on device, needle used in patients artery or vein Infection status of source Class 1: asymptomatic HIV infection or known low viral load (<1,500 copies/mL) Class 2: symptomatic HIV, AIDS, acute seroconversion, or known high viral load The selection of a drug regimen for HIV PEP must balance the risk for infection against the potential toxicities of the agent(s) used. Because PEP is potentially toxic, its use is not justified for exposures that pose a negligible risk for transmission (Tables 1 and 2). The initial HIV PEP regimens recommended in these guidelines should be viewed as suggestions that can be changed if additional information is obtained concerning the source of the occupational exposure (e.g., possible treatment history or antiretroviral drug resistance) or if expert consultation is provided. Given the complexity of choosing and administering HIV PEP, whenever possible, consultation with an infectious diseases consultant or another physician who has experience with antiretroviral agents is recommended, but it should not delay timely initiation of PEP. Consideration should be given to the comparative risk represented by the exposure and information regarding the exposure source, including history of and response to antiretroviral therapy based on clinical response, CD4+ T-cell counts, viral load measurements, and current disease stage. When the source persons virus is known or suspected to be resistant to one or more of the drugs considered for the PEP regimen, the selection of drugs to which the source persons virus is unlikely to be resistant is recommended; expert consultation is advised. If this information is not immediately available, initiation of PEP, if indicated, should not be delayed; changes in the regimen can be made after PEP has started, as appropriate. For HCP who initiate PEP, re-evaluation of the exposed person should occur within 72 hours postexposure, especially if additional information about the exposure or source person becomes available. The selection of a drug regimen for HIV PEP must balance the risk for infection against the potential toxicities of the agent(s) used. Because PEP is potentially toxic, its use is not justified for exposures that pose a negligible risk for transmission (Tables 1 and 2). The initial HIV PEP regimens recommended in these guidelines should be viewed as suggestions that can be changed if additional information is obtained concerning the source of the occupational exposure (e.g., possible treatment history or antiretroviral drug resistance) or if expert consultation is provided. Given the complexity of choosing and administering HIV PEP, whenever possible, consultation with an infectious diseases consultant or another physician who has experience with antiretroviral agents is recommended, but it should not delay timely initiation of PEP. Consideration should be given to the comparative risk represented by the exposure and information regarding the exposure source, including history of and response to antiretroviral therapy based on clinical response, CD4+ T-cell counts, viral load measurements, and current disease stage. When the source persons virus is known or suspected to be resistant to one or more of the drugs considered for the PEP regimen, the selection of drugs to which the source persons virus is unlikely to be resistant is recommended; expert consultation is advised. If this information is not immediately available, initiation of PEP, if indicated, should not be delayed; changes in the regimen can be made after PEP has started, as appropriate. For HCP who initiate PEP, re-evaluation of the exposed person should occur within 72 hours postexposure, especially if additional information about the exposure or source person becomes available.

    15. December 2007 AETC National Resource Center, www.aidsetc.org PEP for Percutaneous Injuries

    16. December 2007 AETC National Resource Center, www.aidsetc.org PEP for Percutaneous Injuries (2)

    17. December 2007 AETC National Resource Center, www.aidsetc.org Which Drugs to Use? Consultation with an expert is recommended Regimens should be chosen to minimize potential drug toxicities and maximize the likelihood of adherence If the source patients virus is known or suspected to be resistant to ARVs, the PEP regimen should consist of drugs to which the sources virus is unlikely to be resistant

    18. December 2007 AETC National Resource Center, www.aidsetc.org Which Drugs to Use? (3) Basic 2-drug regimens: Preferred: ZDV + 3TC or FTC TDF + 3TC or FTC Alternative: d4T + 3TC or FTC ddI + 3TC or FTC PHS continues to recommend stratification of HIV PEP regimens based on the severity of exposure and other considerations (e.g., concern for antiretroviral drug resistance in the exposure source). The majority of HIV exposures will warrant a two-drug regimen, using two NRTIs or one NRTI and one NtRTI (Tables 1 and 2; Appendix). Combinations that can be considered for PEP include ZDV and 3TC or emtricitabine (FTC); d4T and 3TC or FTC; and tenofovir (TDF) and 3TC or FTC. In the previous PHS guidelines, a combination of d4T and ddI was considered one of the firstchoice PEP regimens; however, this regimen is no longer recommended because of concerns about toxicity (especially neuropathy and pancreatitis) and the availability of more tolerable alternative regimens (3).PHS continues to recommend stratification of HIV PEP regimens based on the severity of exposure and other considerations (e.g., concern for antiretroviral drug resistance in the exposure source). The majority of HIV exposures will warrant a two-drug regimen, using two NRTIs or one NRTI and one NtRTI (Tables 1 and 2; Appendix). Combinations that can be considered for PEP include ZDV and 3TC or emtricitabine (FTC); d4T and 3TC or FTC; and tenofovir (TDF) and 3TC or FTC. In the previous PHS guidelines, a combination of d4T and ddI was considered one of the firstchoice PEP regimens; however, this regimen is no longer recommended because of concerns about toxicity (especially neuropathy and pancreatitis) and the availability of more tolerable alternative regimens (3).

    19. December 2007 AETC National Resource Center, www.aidsetc.org Which Drugs to Use? (4) Expanded =3-drug PEP regimens: Preferred: LPV/RTV (Kaletra) + basic 2-drug regimen Alternative: ATV* RTV FPV RTV IDV** RTV SQV + RTV NFV*** EFV*** The addition of a third (or even a fourth) drug should be considered for exposures that pose an increased risk for transmission or that involve a source in whom antiretroviral drug resistance is likely. The addition of a third drug for PEP after a high-risk exposure is based on demonstrated effectiveness in reducing viral burden in HIV-infected persons. However, no definitive data exist that demonstrate increased efficacy of three- compared with two-drug HIV PEP regimens. Previously, IDV, nelfinavir (NFV), EFV, or abacavir (ABC) were recommended as first-choice agents for inclusion in an expanded PEP regimen (3). PHS now recommends that expanded PEP regimens be PIbased. The PI preferred for use in expanded PEP regimens is lopinavir/ritonavir (LPV/RTV). Other PIs acceptable for use in expanded PEP regimens include atazanavir, fosamprenavir, RTV-boosted IDV, RTV-boosted SQV, or NFV (Appendix). Although side effects are common with NNRTIs, EFV may be considered for expanded PEP regimens, especially when resistance to PIs in the source persons virus is known or suspected. Caution is advised when EFV is used in women of childbearing age because of the risk of teratogenicity. Drugs that may be considered as alternatives to the expanded regimens, with warnings about side effects and other adverse events, are EFV or PIs as noted in the Appendix in combination with ddl and either 3TC or FTC. The fusion inhibitor enfuvirtide (T20) has theoretic benefits for use in PEP because its activity occurs before viral-host cell integration; however, it is not recommended for routine HIV PEP because of the mode of administration (subcutaneous injection twice daily). Furthermore, use of T20 has the potential for production of anti-T20 antibodies that cross react with HIV gp41. This could result in a false-positive, enzyme immunoassay (EIA) HIV antibody test among HIV-uninfected patients. A confirmatory Western blot test would be expected to be negative in such cases. T20 should only be used with expert consultation. From the Morbidity and Mortality Weekly Report (MMWR) <http://www.cdc.gov/mmwr/index.html> December 14, 2007 / 56(49);1291-1292 : on September 10, 2007, Pfizer, Inc. issued a letter* warning health-care providers about the use of Viracept (nelfinavir) (Pfizer, Inc., New York, New York), another protease inhibitor, because the Viracept manufactured in Europe contained high levels of ethyl methane mesylate (EMS). EMS is a byproduct of the manufacturing process and a known animal carcinogen, mutagen, and teratogen. The level at which EMS might become carcinogenic or teratogenic in humans is not known. The warning in the letter applies to pregnant women and states that information about the ability of EMS to cross the placenta or to enter breast milk is currently unknown. A review of data from the Antiretroviral Pregnancy Registry, which collects data on approximately 6,000 HIV-infected pregnant women, indicated that, during January 1989--January 2007, no statistically significant difference was observed in the prevalence of birth defects among the infants of women who used Viracept compared with those whose mothers used other antiretroviral therapies (3). Nonetheless, the Food and Drug Administration (FDA) recommends that pregnant women limit their exposure to EMS during pregnancy. Until further notice, pregnant women who need to begin antiretroviral therapy or HIV PEP should not be offered regimens containing Viracept. As a precautionary measure, pregnant women currently receiving Viracept should be switched to an alternative antiretroviral therapy while Pfizer and FDA work to implement a long-term EMS specification for Viracept. Specific recommendations for use of antiretroviral agents in pregnant HIV-1--infected patients are indicated in the U.S. Department of Health and Human Services guidelines (4) and can be consulted to determine an alternative treatment option. Because nearly 80% of U.S. health-care personnel are female (5) and many of these women are of child-bearing age, this updated information about Viracept might be relevant to the choice of drugs included in an HIV PEP regimen taken by female health-care personnel. Additional information and guidance regarding management of specific exposures are available from the National Clinicians' Post-Exposure Prophylaxis Hotline by telephone (888-448-4911) or online (http://www.ucsf.edu/hivcntr). The addition of a third (or even a fourth) drug should be considered for exposures that pose an increased risk for transmission or that involve a source in whom antiretroviral drug resistance is likely. The addition of a third drug for PEP after a high-risk exposure is based on demonstrated effectiveness in reducing viral burden in HIV-infected persons. However, no definitive data exist that demonstrate increased efficacy of three- compared with two-drug HIV PEP regimens. Previously, IDV, nelfinavir (NFV), EFV, or abacavir (ABC) were recommended as first-choice agents for inclusion in an expanded PEP regimen (3). PHS now recommends that expanded PEP regimens be PIbased. The PI preferred for use in expanded PEP regimens is lopinavir/ritonavir (LPV/RTV). Other PIs acceptable for use in expanded PEP regimens include atazanavir, fosamprenavir, RTV-boosted IDV, RTV-boosted SQV, or NFV (Appendix). Although side effects are common with NNRTIs, EFV may be considered for expanded PEP regimens, especially when resistance to PIs in the source persons virus is known or suspected. Caution is advised when EFV is used in women of childbearing age because of the risk of teratogenicity. Drugs that may be considered as alternatives to the expanded regimens, with warnings about side effects and other adverse events, are EFV or PIs as noted in the Appendix in combination with ddl and either 3TC or FTC. The fusion inhibitor enfuvirtide (T20) has theoretic benefits for use in PEP because its activity occurs before viral-host cell integration; however, it is not recommended for routine HIV PEP because of the mode of administration (subcutaneous injection twice daily). Furthermore, use of T20 has the potential for production of anti-T20 antibodies that cross react with HIV gp41. This could result in a false-positive, enzyme immunoassay (EIA) HIV antibody test among HIV-uninfected patients. A confirmatory Western blot test would be expected to be negative in such cases. T20 should only be used with expert consultation. From the Morbidity and Mortality Weekly Report (MMWR) <http://www.cdc.gov/mmwr/index.html> December 14, 2007 / 56(49);1291-1292 : on September 10, 2007, Pfizer, Inc. issued a letter* warning health-care providers about the use of Viracept (nelfinavir) (Pfizer, Inc., New York, New York), another protease inhibitor, because the Viracept manufactured in Europe contained high levels of ethyl methane mesylate (EMS). EMS is a byproduct of the manufacturing process and a known animal carcinogen, mutagen, and teratogen. The level at which EMS might become carcinogenic or teratogenic in humans is not known. The warning in the letter applies to pregnant women and states that information about the ability of EMS to cross the placenta or to enter breast milk is currently unknown. A review of data from the Antiretroviral Pregnancy Registry, which collects data on approximately 6,000 HIV-infected pregnant women, indicated that, during January 1989--January 2007, no statistically significant difference was observed in the prevalence of birth defects among the infants of women who used Viracept compared with those whose mothers used other antiretroviral therapies (3). Nonetheless, the Food and Drug Administration (FDA) recommends that pregnant women limit their exposure to EMS during pregnancy. Until further notice, pregnant women who need to begin antiretroviral therapy or HIV PEP should not be offered regimens containing Viracept. As a precautionary measure, pregnant women currently receiving Viracept should be switched to an alternative antiretroviral therapy while Pfizer and FDA work to implement a long-term EMS specification for Viracept. Specific recommendations for use of antiretroviral agents in pregnant HIV-1--infected patients are indicated in the U.S. Department of Health and Human Services guidelines (4) and can be consulted to determine an alternative treatment option. Because nearly 80% of U.S. health-care personnel are female (5) and many of these women are of child-bearing age, this updated information about Viracept might be relevant to the choice of drugs included in an HIV PEP regimen taken by female health-care personnel. Additional information and guidance regarding management of specific exposures are available from the National Clinicians' Post-Exposure Prophylaxis Hotline by telephone (888-448-4911) or online (http://www.ucsf.edu/hivcntr).

    20. December 2007 AETC National Resource Center, www.aidsetc.org Resources for Consultation Local experts identified for PEP (eg, ID consultant, hospital epidemiologist) National Clinicians Postexposure Prophylaxis Hotline (PEPline) 24-hour telephone consultation service: 888-448-4911

    21. December 2007 AETC National Resource Center, www.aidsetc.org Follow-Up of Exposed HCP All exposed HCP should receive the following, regardless of whether they receive PEP: Follow-up counseling, postexposure testing, and medical evaluation HIV-antibody testing (EIA) to monitor for seroconversion: at baseline, 6 weeks, 12 weeks, and 6 months after exposure; ` HIV testing if exposed HCP develops illness compatible with acute retroviral syndrome HCP with occupational exposure to HIV should receive follow-up counseling, postexposure testing, and medical evaluation regardless of whether they receive PEP. HIV-antibody testing by enzyme immunoassay should be used to monitor HCP for seroconversion for >6 months after occupational HIV exposure. After baseline testing at the time of exposure, follow- up testing could be performed at 6 weeks, 12 weeks, and 6 months after exposure. Extended HIV follow-up (e.g., for 12 months) is recommended for HCP who become infected with HCV after exposure to a source coinfected with HIV and HCV. Whether extended follow-up is indicated in other circumstances (e.g., exposure to a source co-infected with HIV and HCV in the absence of HCV seroconversion or for exposed persons with a medical history suggesting an impaired ability to mount an antibody response to acute infection) is unclear. Although rare instances of delayed HIV seroconversion have been reported (56,57), the infrequency of this occurrence does not warrant adding to exposed persons anxiety by routinely extending the duration of postexposure follow-up. However, this should not preclude a decision to extend follow-up in a particular situation based on the clinical judgment of the exposed persons health-care provider. The routine use of direct virus assays (e.g., HIV p24 antigen EIA or tests for HIV ribonucleic acid) to detect infection among exposed HCP usually is not recommended (58). Despite the ability of direct virus assays to detect HIV infection a few days earlier than EIA, the infrequency of occupational seroconversion and increased costs of these tests do not warrant their routine use in this setting. In addition, the relatively high rate of false-positive results of these tests in this setting could lead to unnecessary anxiety or treatment (59,60). Nevertheless, HIV testing should be performed on any exposed person who has an illness compatible with an acute retroviral syndrome, regardless of the interval since exposure. A person in whom HIV infection is identified should be referred for medical management to a specialist with expertise in HIV treatment and counseling. Health-care providers caring for persons with occupationally acquired HIV infection can report these cases to CDC at telephone 800-893-0485 or to their state health departments. HCP with occupational exposure to HIV should receive follow-up counseling, postexposure testing, and medical evaluation regardless of whether they receive PEP. HIV-antibody testing by enzyme immunoassay should be used to monitor HCP for seroconversion for >6 months after occupational HIV exposure. After baseline testing at the time of exposure, follow- up testing could be performed at 6 weeks, 12 weeks, and 6 months after exposure. Extended HIV follow-up (e.g., for 12 months) is recommended for HCP who become infected with HCV after exposure to a source coinfected with HIV and HCV. Whether extended follow-up is indicated in other circumstances (e.g., exposure to a source co-infected with HIV and HCV in the absence of HCV seroconversion or for exposed persons with a medical history suggesting an impaired ability to mount an antibody response to acute infection) is unclear. Although rare instances of delayed HIV seroconversion have been reported (56,57), the infrequency of this occurrence does not warrant adding to exposed persons anxiety by routinely extending the duration of postexposure follow-up. However, this should not preclude a decision to extend follow-up in a particular situation based on the clinical judgment of the exposed persons health-care provider. The routine use of direct virus assays (e.g., HIV p24 antigen EIA or tests for HIV ribonucleic acid) to detect infection among exposed HCP usually is not recommended (58). Despite the ability of direct virus assays to detect HIV infection a few days earlier than EIA, the infrequency of occupational seroconversion and increased costs of these tests do not warrant their routine use in this setting. In addition, the relatively high rate of false-positive results of these tests in this setting could lead to unnecessary anxiety or treatment (59,60). Nevertheless, HIV testing should be performed on any exposed person who has an illness compatible with an acute retroviral syndrome, regardless of the interval since exposure. A person in whom HIV infection is identified should be referred for medical management to a specialist with expertise in HIV treatment and counseling. Health-care providers caring for persons with occupationally acquired HIV infection can report these cases to CDC at telephone 800-893-0485 or to their state health departments.

    22. December 2007 AETC National Resource Center, www.aidsetc.org Follow-Up of Exposed HCP (3) Psychologic impact of occupational exposure to HIV may be substantial; psychologic counseling should be an essential component of the management and care of exposed HCP

    23. Pre-Exposure Prophylaxis iPrEX study 2008-2010 enrolled 2,499 HIV negative MSM engaged in high-risk sexual behavior Participants were randomized to take daily tenofovir/emtricitabine (Truvada) or placebo Visits every 4 weeks with HIV testing, risk-reduction counseling, dispensing of pills and condoms Average follow-up 1.2 years Results: overall 44% reduction in new HIV infections in the PrEP arm; risk reduction strongly related to adherence (73% for those with adherence >90% vs. 21% for those with <90% adherence) December 2007 AETC National Resource Center, www.aidsetc.org

    24. CASE STUDY December 2007 AETC National Resource Center, www.aidsetc.org

    26. Post-exposure Prophylaxis Case 2: Initial Evaluation and Post-exposure Prophylaxis PEP is not indicated at this time because too much time has elapsed since the exposure. PEP should be initiated if viral load testing on the source patient reveals a high viral load. A two-drug PEP regimen should be initiated immediately. A three-drug PEP regimen should be initiated immediately.

    28. This presentation must be evaluated using the HIV 101 evaluation which may be found at the following WEBSITE (use all lowercase letters) http://www.surveymonkey.com/s/9FMWRCShiv10112aug2011 EVALUATION DEADLINE 11:00 p.m. Friday, August 19, 2011 December 2007 AETC National Resource Center, www.aidsetc.org