COMMENTARY

HIV Prophylaxis Following Non-occupational Exposure: Guideline and Commentary

Samuel T. Merrick, MD

Disclosures

October 24, 2013

In This Article

HIV Prophylaxis Following Non-occupational Exposure: Expert Commentary

What follows is an update to the New York State Department of Health guidelines on HIV Prophylaxis Following Non-occupational Exposure (nPEP). While avoidance of exposure to HIV remains the best way to prevent transmission, given the challenges inherent in changing human behavior, prevention methods must be as broad and comprehensive as possible to have a realistic hope of slowing and eliminating this devastating pandemic.

Since the publication of the last iteration of these guidelines, there has been an explosion of information on preventing HIV through pre-exposure prophylaxis (PrEP),1-3 including approval by the US Food and Drug Administration of tenofovir-emtricitabine to be used in this setting; the development of more potent and better tolerated medications; more precise estimates of the risk for transmission based on type of exposure4; evidence that effective treatment is a prevention tool5; and more widespread access to antiretroviral therapy (ART) worldwide, including for the prevention of mother-to-child transmission.

All of this has led to growing optimism that using a multi-faceted approach that includes robust prevention education, increased testing, earlier treatment, effective linkage to care, and both pre- and post-exposure prophylaxis in appropriately selected individuals may ultimately lead to an "AIDS-Free Generation."6 In parallel to these developments has been the demonstration of proof of concept for HIV cure,7,8 although a cost-effective and safe method for either eradication or functional cure is probably many years away.

No randomized controlled trials have been done to establish the efficacy of nPEP because of the ethical issues created by the knowledge that PEP in the occupational setting (oPEP) reduced rates of transmission.9 However, this demonstrated efficacy of oPEP, as well as compelling animal evidence,10-12 supports the use of nPEP, and it is -- and should be -- standard practice for non-occupational exposures deemed to be high risk. Importantly, there is no evidence that the availability of nPEP leads to an increase in high-risk behavior.13 Frustratingly, awareness of nPEP in communities at risk, among healthcare providers, and in emergency room settings continues to be less than ideal14-15; education about and access to effective nPEP must remain a priority.

Patients presenting for nPEP give providers an invaluable opportunity to do baseline HIV testing, provide education and counseling about risk behaviors, evaluate for possible PrEP, and perhaps most important, to attempt to engage patients in ongoing medical care to address other problems that may exist, such as substance use and mental health issues. These patients are a group that may have HIV already and have been found to have elevated future risk for both HIV seroconversion16 and acquisition of other sexually transmitted diseases, including hepatitis C. Acute hepatitis C has now reached epidemic levels in some populations of men who have sex with men17 (although it may be that it is simply being detected more frequently18).

Even if prophylaxis is not indicated, these encounters may represent a rare contact with the healthcare system for an at-risk individual who could benefit from ongoing care, education, and counseling.

Although rates of completion for 28 days of nPEP are generally higher than the rates found in oPEP studies, tolerability of older regimens has remained a significant problem. This update addresses that with a key change -- recommending that the preferred regimen include tenofovir, emtricitabine (or lamivudine), and raltegravir, agents that are extremely well tolerated and have been shown to result in higher completion rates in all PEP settings.19,20

This update also highlights the importance of timely consultation with experts in the treatment of HIV. In addition to knowledge about and access to PEP, proper assessment of risk, forewarning of possible side effects and how to manage them, and counseling on adhering to the full 28-day course are vital and best managed by a provider with experience in this setting.

Some patients may under- or overestimate the actual risk of the presenting exposure21; given the high stakes, proper selection for nPEP is vital. Just as crucial are situations in which the source patient may be known to have HIV or may have had a recent exposure and could possibly have acute infection, raising the risk for transmission significantly.

The decision-making process can be complex and time-sensitive, and although these guidelines provide a very clear series of steps -- evaluation of risk, appropriate testing in all possible scenarios based on source availability and serostatus, evaluation for other sexually transmitted diseases, and treatment and follow-up -- primary care providers may not have significant experience in this setting. If appropriate expert guidance is not readily available locally, providers can call the National Clinicians' Consultation Center PEPline at 888-448-4911.

Other important changes in this guideline, in addition to a new preferred regimen, include:

  1. Recommendation for the use of HIV RNA testing to assess available source patients who may have had recent high-risk exposures but test negative with antibody based tests at baseline;

  2. Follow-up HIV testing no longer needed at 6 months for the exposed patient;

  3. A clear table outlining exposures appropriate for nPEP and an appendix with estimated risks of various exposures, as well as factors that may increase risk;

  4. Recommendation to consider PrEP for patients who present with repeated high-risk behavior or for repeat courses of nPEP; and

  5. Updated guidance regarding payment options for nPEP.

Significant challenges remain in reducing new HIV infections. These updated guidelines provide a clear roadmap for one important aspect of the necessary comprehensive approach to reduce and eliminate HIV for future generations.

References

  1. Baeten JM, Donnell D, Ndase P, et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med. 2012;367:399-410.

  2. Choopanya K, Martin M, Suntharasamai P, et al. Antiretroviral prophylaxis for HIV infection in injecting drug users in Bangkok, Thailand (the Bangkok Tenofovir Study): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2013;381:2083-2090.

  3. Grant RM, Lama JR, Anderson PL, et al. Pre-exposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med. 2010;363:2587-2599.

  4. Centers for Disease Control and Prevention. HIV Transmission Risk. July 11, 2013. http://www.cdc.gov/hiv/policies/law/risk.html Accessed September 23, 2013.

  5. Cohen MS, Chen YQ, McCauley M, et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med. 2011;365:493-505.

  6. Clinton HR. Creating an AIDS-Free Generation. Remarks at the National Institutes of Health's Masur Auditorium, Bethesda, Maryland. November 8, 2011. http://www.state.gov/secretary/rm/2011/11/176810.htm Accessed September 23, 2013.

  7. Hütter G, Nowak D, Mossner M, et al. Long-term control of HIV by CCR5 Delta32/Delta32 stem-cell transplantation. N Engl J Med. 2009;360:692-698.

  8. Persaud D, Gay H, Ziemniak CF, et al. Functional HIV cure after very early ART of an infected infant. Program and abstracts of the 20th Conference on Retroviruses and Opportunistic Infections; March 3-6, 2013; Atlanta, Georgia. Abstract 48LB.

  9. Cardo DM, Culver DH, Ciesielski CA, et al. A case-control study of HIV seroconversion in health care workers after percutaneous exposure: Centers for Disease Control and Prevention Needlestick Surveillance Group. N Engl J Med. 1997;337:1485-1490.

  10. Otten RA, Smith DK, Adams DR, et al. Efficacy of postexposure prophylaxis after intravaginal exposure of pig-tailed macaques to a human-derived retrovirus (human immunodeficiency virus type 2). J Virol. 2000;74:9771-9775.

  11. Smith MS, Foresman L, Lopez GJ, et al. Lasting effects of transient postinoculation tenofovir [9-R-(2-Phosphonomethoxypropyl)adenine] treatment on SHIV (KU2) infection of rhesus macaques. Virology. 2000;277:306-315.

  12. Van Rompay KK, Miller MD, Marthas ML, et al. Prophylactic and therapeutic benefits of short-term 9-[2-(R)-(phosphonomethoxy) propyl]adenine (PMPA) administration to newborn macaques following oral inoculation with simian immunodeficiency virus with reduced susceptibility to PMPA. J Virol. 2000;74:1767-1774.

  13. Schechter M, do Lago RF, Mendelsohn AB, et al. Behavioral impact, acceptability, and HIV incidence among homosexual men with access to postexposure chemoprophylaxis for HIV. J Acquir Immune Defic Syndr. 2004;35:519-525.

  14. Donnell D, Mimiaga MJ, Mayer K, et al. Use of non-occupational post-exposure prophylaxis does not lead to an increase in high risk sex behaviors in men who have sex with men participating in the EXPLORE trial. AIDS Behav. 2010;14:1182-1189.

  15. Mehta SA, Silvera R, Bernstein K, et al. Awareness of post-exposure HIV prophylaxis in high-risk men who have sex with men in New York City. Sex Transm Infect. 2011;87:344-348.

  16. Heuker J, Sonder GJ, Stolte I, et al. High HIV incidence among MSM prescribed postexposure prophylaxis, 2000-2009: indications for ongoing sexual risk behaviour. AIDS. 2012;26:505-512.

  17. Bradshaw D, Matthews G, Danta M. Sexually transmitted hepatitis C infection: the new epidemic in MSM? Curr Opin Infect Dis. 2013;26:66-72.

  18. Witt MD, Seaberg EC, Darilay A, et al. Incident hepatitis C virus infection in men who have sex with men: a prospective cohort analysis, 1984-2011. Clin Infect Dis. 2013;57:77-84.

  19. Mayer KH, Mimiaga MJ, Gelman M, et al. Raltegravir, tenofovir DF, and emtricitabine for postexposure prophylaxis to prevent the sexual transmission of HIV: safety, tolerability, and adherence. J Acquir Immune Defic Syndr. 2012;59:354-359

  20. McAllister J, Read P, McNulty A, et al. Raltegravir-emtricitabine-tenofovir as HIV nonoccupational post-exposure prophylaxis in men who have sex with men: safety, tolerability and adherence. HIV Med. 2013 Sep 6. [Epub ahead of print]

  21. Cohen SE, Liu AY, Bernstein KT, et al. Preparing for HIV pre-exposure prophylaxis: lessons learned from post-exposure prophylaxis. Am J Prev Med. 2013; 44(1 suppl 2):S80-S85.

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