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Postexposure prophylaxis for HIV: Pivotal intervention for those at risk

Sharifi-Azad, Jessica RPA-C; Rizzolo, Denise PhD, PA-C

Journal of the American Academy of PAs: August 2011 - Volume 24 - Issue 8 - p 22–25
CME Postexposure prophylaxis
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LEARNING OBJECTIVES 
  • Discuss the types of exposure that would necessitate HIV postexposure prophylaxis
  • Review the currently recommended HIV postexposure prophylaxis regimens
  • Provide resources for clinicians who have questions about postexposure prophylaxis
  • Describe follow-up for patients taking HIV prophylaxis medications

Discuss the types of exposure that would necessitate HIV postexposure prophylaxisReview the currently recommended HIV postexposure prophylaxis regimensProvide resources for clinicians who have questions about postexposure prophylaxisDescribe follow-up for patients taking HIV prophylaxis medications Postexposure prophylaxis is about 81% effective in preventing seroconversion to acute HIV infection. But when is it appropriate, how is it executed, and what follow-up is needed?

Jessica Sharifi-Azad is a physician assistant at sunrise Medical group, New York, NY. she is a graduate of the Pace university-Lenox Hill Hospital PA program. Denise Rizzolo is an assistant clinical professor at Pace and an associate professor at the Seton Hall university PA program. The authors have indicated no relationships to disclose relating to the content of this article.

SymbolSEE THE ONLINE VERSION OF THIS ARTICLE TO LINK TO

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PEPline: The National Clinicians’ Post-Exposure Prophylaxis Hotline www.nccc.ucsf.edu/about_nccc/pepline

AIDS Treatment Information Service www.aidsinfo.nih.gov

New York State Department of Health quick reference card www.hivguidelines.org/wp-content/uploads/2009/05/pepcard1.jpg

In the early 1990s, postexposure prophylaxis (PEP) was used solely in health care workers who had been occupationally exposed to the human immunodeficiency virus. Since then, however, providing antiretroviral (ARV) therapy as a prophylactic measure to those exposed to HIV through sexual contact or IV drug use has become widely accepted. Since seroconversion does not occur instantaneously, a short window may be present after HIV exposure where proper prophylactic measures may avert fusion of the virus into the cell.1 Observational data demonstrate that postexposure prophylaxis is about 81% effective in preventing seroconversion to acute HIV infection.2 But when is prophylactic therapy appropriate? How is PEP executed, and what follow-up is needed? The answers to these and related questions can be confusing. This article discusses which types of exposures should result in prophylactic therapy, optimal antiretroviral medications for treatment, duration of prophylactic treatment, and follow-up management.

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WHEN TO CONSIDER ANTIRETROVIRAL PROPHYLAXIS

Both occupational and nonoccupational exposures have the potential to transmit HIV and may require prophylactic treatment. Occupational exposures are overt, most commonly involving percutaneous needlesticks in the health care setting. Less commonly, occupational exposure can occur through exposure to infected body fluid such as semen, vaginal secretions, breast milk, CSF, and pleural, peritoneal, pericardial, synovial, or amniotic fluids.3 Higher rates of viral transmission to the exposed person are associated with advanced HIV disease (high viral load and low CD4+ T-cell count) in the source patient, deeper puncture wounds, obvious blood on the needle/instrument, and use of the needle in the source patient’s blood vessel.1 The amount of visible blood and depth of puncture are directly proportional to the risk of infection. Thus, an exposure involving a shallow puncture wound or without obvious blood on the instrument suggests a lower risk.

Nonoccupational exposures can occur from unprotected sexual contact or sharing needles with an HIV-infected person. Being the receptive partner during anal or vaginal intercourse poses a much higher risk of infection than being the insertive partner. Repeated exposure to shared needles is also riskier than an isolated exposure (Table 1).

TABLE 1

TABLE 1

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Figure

Exposed persons who know definitively that they were HIV-negative prior to exposure—that is, they received serologic confirmation of negative status within the past 6 months—require HIV prophylaxis. Exposed persons who believe they are HIV-negative but are not certain—that is, they have had no recent serologic test for HIV or have never been tested—should have a rapid ELISA (enzyme-linked immunosorbent assay) performed before starting postexposure prophylaxis. If a rapid antibody test is not available, PEP should be initiated immediately pending results. If the exposed person is already seropositive, prophylactic treatment is not warranted.

In occupational settings, the source patient is often available for immediate testing via rapid ELISA to determine HIV status. If the ELISA result is negative, PEP is generally not recommended.3 However, if the source patient engages in high-risk behavior and may have HIV infection but not yet be antibody positive, the exposed person should begin PEP. If rapid HIV testing is not immediately available, PEP should always be initiated, regardless of the status of the source patient, while test results are pending.1 If a negative result is returned, PEP may then be discontinued.

In nonoccupational settings, source patients are not likely to be available for testing. PEP is always advised if the source patient belongs to one of the following high-risk populations: men who have sex with men, men who have sex with both men and women, commercial sex workers, IV drug users, former prisoners, and natives of a country where HIV prevalence is 1% or greater. Since perpetrators of sexual crimes are at high risk for being infected with HIV, any victim of sexual assault should also undergo PEP.1 In a study done in Brazil, 180 women who were victims of sexual assault were treated with combinations of zidovudine (Retrovir, generics), lamivudine (Epivir), and indinavir (Crixivan). These women remained seronegative whereas 4 of 145 untreated women seroconverted.4

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PEP TREATMENT GUIDELINES

Postexposure prophylaxis should be started as soon as possible following the exposure to potential HIV infection. According to most guidelines (including those from the World Health Organization and the CDC), PEP should be initiated within 72 hours after the exposure and continued for 28 days or roughly 4 weeks.1,5 However, some guidelines—such as those from the New York State Department of Health and Mental Hygiene—insist that PEP should be initiated within 36 hours of exposure for optimal prevention.6 This recommendation is based on an animal study which concluded that starting PEP within 12, 24, or 36 hours was more effective at inhibiting seroconversion than starting at 48 to 72 hours.6

PEP regimens Although a regimen of three antiretroviral medications is currently used to treat patients with chronic HIV disease, the same is not true for postexposure prophylaxis. Ideal antiretroviral regimens would balance the cost of the medication, its efficacy in providing prophylaxis, and the side effects it may cause. A three-drug regimen may be difficult to tolerate and therefore may lead to premature discontinuation. A single-drug regimen is not recommended because it carries a high risk of resistance. Two-drug regimens are the best option for PEP because they offer increased efficacy with fewer side effects. In most situations, however, no matter whether the exposure is occupational or nonoccupational, the HIV status of the source patient is unknown or cannot be determined. In these situations, a three-drug regimen is recommended (Table 2).

TABLE 2

TABLE 2

“Two-drug regimens offer easier dosing, resulting in improved adherence, fewer side effects, and reduced costs for treatment.”

Two-drug regimens are advised for postexposure prophylaxis in the following situations (both occupational and nonoccupational): the background prevalence of ARV drug resistance in the community is less than 15%, the source patient has never used ARV therapy, and the source patient is not likely to have HIV resistance to ARV therapy based on history.1 Additionally, two-drug regimens offer easier dosing, resulting in improved adherence, fewer side effects, and lower cost.6 A standard two-drug prophylactic regimen consists of two nucleoside (nucleotide) reverse transcriptase inhibitors (N[t]RTIs), which are often available as monotherapy in a single pill. Most commonly, either tenofovir (300 mg)/emtricitabine (200 mg) (Truvada, 1 tablet per day) or zidovudine (300 mg)/lamivudine (150 mg) (Combivir, 1 tablet twice daily) is used.1,6

Although a three-drug regimen is not ideal, it is indicated in the following situations: resistance to antiretroviral therapy is suspected or confirmed; the source patient is confirmed to be HIV positive, is taking ARV medications, and is known to have resistance; the source patient’s HIV status is unknown; or the background prevalence of resistance to ARV therapy in the community exceeds 15%.1 Three-drug regimens combine two N[t]RTIs with a boosted protease inhibitor. The protease inhibitor adds only a small amount of potency to the regimen at the cost of increased adverse effects, making adherence more challenging. However, if a high level of resistance is suspected, use of a protease inhibitor will provide prophylaxis where one of the N[t]RTI drugs has failed.6

Zidovudine/lamivudine and tenofovir/emtricitabine are first-line choices as the N[t]RTI backbone in a three-drug regimen. According to the World Health Organization, the boosted protease inhibitor of choice is lopinavir (200 mg) combined with ritonavir (50 mg) (Kaletra, 2 tablets twice daily or 4 tablets once daily). Other boosted protease inhibitor options are darunavir (Prezista, 800 mg per day) or atazanavir (Reyataz, 300 mg per day) boosted with ritonavir (Norvir, 100 mg per day).1,6

Follow-up testing The rate of adherence to PEP is estimated to be about 50%.5 Nonadherence is usually a result of dosing difficulty or inability to tolerate adverse effects.5 To improve compliance, weekly follow-up is suggested for the duration of treatment. This schedule allows patients to discuss difficulties they are having with the regimen and makes them less likely to stop taking the medication. During the follow-up visits, clinicians should discuss possible side effects (most commonly nausea and fatigue) and prescribe antiemetics if needed. Reducing adverse effects will most likely increase the likelihood of compliance. Psychological counseling should also be offered since being exposed to HIV can be a traumatic experience.6

HIV serology testing should be performed via ELISA at baseline, 4 to 6 weeks after exposure, 3 months after exposure, and finally at 6 months after the initial exposure. Patients should be educated about the importance of condom use and instructed to avoid sharing items such as needles, razors, and toothbrushes for the full 6 months following exposure, as seroconversion can take up to this long to occur.1

PEP failure rates Higher levels of PEP failure are attributed to a number of factors. Among these are delayed initiation of postexposure prophylaxis, being the receptive partner during anal intercourse, repeated exposure (such as repeated unprotected sexual contact with an HIV-positive person), and nonadherence to the prescribed ARV regimen.7

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KEY POINTS

  • Observational data demonstrate that postexposure prophylaxis is about 81% effective in preventing seroconversion to acute HIV infection.
  • Most guidelines say PEP should be initiated within 72 hours after the exposure and continued for 28 days or roughly 4 weeks. Others insist that PEP should be initiated within 36 hours of exposure for optimal prevention.
  • Two-drug and three-drug regimens are available. Compared to three-drug regimens, two-drug regimens offer lower cost, fewer side effects, and improved adherence but are often not the optimal choice.
  • The regimen should be chosen based on factors such as the prevalence of antiretroviral drug resistance in the community, whether the source patient’s HIV status is known, and the source patient’s treatment history. Close follow-up and periodic antibody testing are essential.
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AVAILABLE RESOURCES

Clinicians with questions about PEP have a number of different resources to choose from:

  • PEPline: The National Clinicians’ Post-Exposure Prophylaxis Hotline is available at www.nccc.ucsf.edu/about_nccc/pepline and at (888) 448-4911, 24 hours per day, 7 days per week. This hotline provides assistance and advice on the proper steps to take when faced with a patient who may need PEP.7
  • The AIDS Treatment Information Service can be reached online at www.aidsinfo.nih.gov, and the FDA can be reached by phone at (800) 332-1088.5
  • A quick reference card, available through the New York State Department of Health, summarizes HIV postexposure prophylaxis protocol. This card can be downloaded at www.hivguidelines.org/wp-content/uploads/2009/05/pepcard1.jpg.7 Having this tool accessible at all offices and hospitals may be useful when initiating PEP.
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CONCLUSION

Postexposure prophylaxis is recommended both for occupational and nonoccupational exposures to HIV. PEP should be reserved for persons who have a plausible possibility of contracting HIV, such as from a confirmed HIV-positive source patient or a source patient with an unknown HIV status who engages in high-risk behavior. Antiretroviral regimens of either two or three medications should be initiated as quickly as possible after the exposure has occurred and continued for a full 4 weeks. Two-drug regimens cause fewer adverse effects and should be used if warranted. If the clinician is unsure which drug regimen is appropriate or requires other assistance, a number of online and phone resources are available. Weekly visits are advised during PEP, and the ELISA should be repeated 4 to 6 weeks, 3 months, and 6 months after the initial exposure. Clinicians should use counseling, follow-up, and all other necessary efforts to promote medication adherence.

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REFERENCES

1. Landovitz RJ, Currier JS. Clinical practice: postexposure prophylaxis for HIV infection. N Engl J Med. 2009;361(18):1768-1775.
2. HIV prophylaxis following non-occupational exposure including sexual assault. HIV Clinical Resource Web site. http://www.hivguidelines.org/clinical-guidelines/post-exposure-prophylaxis/hiv-prophylaxis-following-non-occupational-exposure-including-sexual-assault. Updated May 2010. Accessed July 14, 2011.
3. Tolle MA, Schwartzwald HL. Postexposure prophylaxis against human immunodeficiency virus. Am Fam Physician. 2010;82(2):161-166.
4. Griffith WE, Ackerman GE, Zoellner CL, Sheffield JS. Sexual assault: a report on human immunodeficiency virus postexposure prophylaxis. Obstet Gynecol International. 2010. doi:10.1155/2010/196963.
5. Updated US Public Health Service guidelines for the management of occupational exposures to HBV, HCV, and HIV and recommendations for postexposure prophylaxis. MMWR Recomm Rpt. 2001;50(RR11);1-42.
6. Post-exposure prophylaxis to prevent HIV infection: joint WHO/ILO guidelines on post-exposure prophylaxis (PEP) to prevent HIV infection. http://www.who.int/hiv/pub/guidelines/PEP/en. Accessed July 14, 2011.
7. HIV prophylaxis following occupational exposure. HIV Clinical Resource Web site. http://www.hivguidelines.org/clinical-guidelines/post-exposure-prophylaxis/hiv-prophylaxis-following-occupational-exposure. Updated May 2010. Accessed July 14, 2011.

Section Description

EARN CATEGORY I CME CREDIT by reading this article and the article beginning on page 44 and successfully completing the posttest on page 50. successful completion is defined as a cumulative score of at least 70% correct. This material has been reviewed and is approved for 1 hour of clinical Category I (Preapproved) CME credit by the AAPA. The term of approval is for 1 year from the publication date of August 2011.

© 2011 American Academy of Physician Assistants.