CME CREDIT NOW AVAILABLE-1.0

AMA PRA Category 1 Credit FOR EACH ISSUE (2 ARTICLES)!!!!!!

By Atsuko Koyama, MD, MPH and Lauren Middlebrooks, MD

According to the 2017 Youth Risk Behavior Survey (YRBS), almost 30% of 9th to 12th graders reported being “currently sexually active,” and only 54% used a condom at their last sexual encounter [1]. Despite improved antiretroviral regimens and HIV pre- and post-exposure prophylaxis (PrEP and PEP), adolescents and young adults continue to make up a quarter of new HIV diagnoses (21%, n=8,090), with the majority of these cases being secondary to male-to-male (MSM) sexual contact [2]. Given the prevalence of sexual activity amongst adolescents who present under a variety of circumstances disclosing past sexual activity, knowledge about non-occupational HIV PEP (nPEP) is relevant and important for all pediatricians.

nPEP Basics

Non-occupational HIV post-exposure prophylaxis significantly decreases the risk of HIV infection after possible exposure. nPEP candidates must be HIV negative, and time from exposure must be < 72 hours. If rapid HIV testing of the exposed person is unavailable to determine HIV status, assume the patient is HIV negative, and offer nPEP. Discontinue medications if the exposed person is determined to be HIV positive at a later date.

Next, determine if the exposure poses a “substantial” HIV risk: 1) Is the exposure source HIV positive? 2) What bodily fluids were involved? 3) What is the site of exposure? If the exposure source is HIV positive, and he/she is currently taking antiretroviral medication, nPEP should be catered to any resistance patterns of the source. If the HIV status of the source is unknown, clinicians must make a case-by-case determination if the exposure poses a “substantial” HIV transmission risk based on the bodily fluids involved, site of exposure, and any other known cofactors [3,4]. See table 1 for per-act HIV risk for specific exposures [5]. If HIV status of source patient is unknown, but there is known MSM or IVDU with needle sharing history, source is high risk. Exposure to urine, nasal secretions, saliva, sweat or tears, that are not visibly contaminated with blood is negligible risk and does NOT warrant nPEP, regardless of HIV status of source.

As pediatric practitioners, screening for sexual abuse and commercial sexual exploitation of children (CSEC) is also of utmost importance as these patients are high risk given possibility of repetitive risk exposures [3,4].

Dosing and duration

The preferred regimen in adolescents and adults consists of tenofovir DF and emtricitabine, in conjunction with raltegravir over 28 days [3,4, 6]. Drugs used for nPEP vary under 12 years of age in the pediatric population.(See Table 2).  For patients with impaired renal function, who are pregnant, or who have a limited pharmacy selection, alternative regimes are recommended and listed in the CDC guidelines [3].

Laboratory Testing and Follow-Up

Patients should be tested for HIV-1, HIV-2 antibodies and antigens via 4th generation screening. If this result is positive or indeterminate, further testing with HIV-1/HIV-2 antibody differentiation assay, Western blot, or indirect immunofluorescence assay is necessary.  When available, rapid testing is recommended, although in recently infected patients, false negative results are possible due to later reactivity.

Due to potential side effects of nPEP, baseline assessment of renal function and hepatic function is warranted.   Antiemetics can also be offered with nPEP regimens to decrease common side effects of GI upset.

Given high risk for co-infection, a comprehensive work-up for concurrent sexually transmitted infections (STIs) is recommended.  Prophylactic treatment for STIs, with emergency contraception if encounter was within 120 hours, is also recommended for adults and adolescents due to poor compliance with follow up visits and increased risk for ascending infections. (See Figure 1).  STI prophylaxis in prepubertal patients is not routinely indicated.

Drug Interactions

Medications metabolized by the liver should be monitored and/or dose adjusted when taken in conjunction with nPEP.   For comprehensive drug interaction information see: https://hiv-druginteractions.org/

Compliance

Overall, studies have shown compliance with nPEP is poor, especially after sexual assault [7-9]. Methods instituted to simplify prescriptions for providers, phone reminders, incorporating medications into daily schedules, and patient-provider contact during the 28-day course have improved adherence[3, 10-12].   For patients experiencing financial barriers, medication assistance programs are available at https://www.pparx.org/hiv_aids_programs.

Confidentiality

In Georgia, minors can consent for STI testing and treatment; however, it is important to inform adolescents that confidentiality may not be guaranteed.  At CHOA, verbal consent from patient (or parent) remains a requirement.  As providers, obtaining patients’ direct phone number and encouraging patients to have open discussions with parents, will decrease possibility of confidentiality breach.

nPEP and PrEP

Pre-exposure HIV prophylaxis (PrEP) was approved in May 2018 for adolescents. PrEP should be considered for HIV negative patients at high risk for HIV after completing nPEP [13,14]. High risk persons are defined as those who have completed several courses of PEP, required PEP in close time intervals, or have an HIV positive partner [13]. Patients who are adherent to PreP do not need PEP.

Conclusion

nPEP is the standard of care for patients with substantial risk for HIV.  Discussing nPEP and PrEP, especially with MSM who are at highest risk of HIV, and educating patients on safe sex practices is essential. Dispensing a full 28-day course of nPEP and providing support and resources for patients throughout the  initiation are ideal.   Thus, continued awareness of providers on appropriate nPEP regimens is expected.

Key points:

1. nPEP should be offered to ALL patients at significant risk for HIV exposure who present within 72 hours of exposure.
2. Tenofovir DF/emtricitabine and raltegravir are recommended for pregnant patients and adolescent ≥ 12 years of age; alternative regimens are available.
3. Be aware of which forms of HIV testing and PEP medications are available at your institution. If possible, give a full 28-day course of medications for improved adherence.
4. PEP should be offered if only sporadic PrEP use or discontinuation at least one week prior to exposure.
5. Emergency contraception, hepatitis and HPV vaccination, and empiric gonorrhea, chlamydia, trichomonas treatment should be considered.

Appendix: Recommended Resources for Clinicians

National Clinician’s Postexposure Prophylaxis Hotline (PEPline) (888) 448-4911

http://nccc.ucsf.edu/clinician-consultation/pep-post-exposure-prophylaxis/

National Clinician Consultation Center, PrEPline (855) 448-7737

http://nccc.ucsf.edu/clinical-resources/prep-guidelines-and-resources/

*********See below to complete CME*************

CME Credit

References and recommended reading:

1. 1. Kann L, McManus T, Harris WA, et al. Youth risk behavior surveillance-United States, 2017. 2018 Jun 15;67(No. 8).
2. 2. HIV Surveillance Report, 2017. Diagnoses of HIV infection in the United States and Dependent Areas, 2017. Report No. 29. Centers for Disease Control and Prevention; 2018; Available at: http://www.cdc.gov/hiv/library/reports/hiv-surveillance.html.[Accessed 19 Feb 2019]
3. 3. Dominguez KL, Smith DK, Thomas V, et al. Updated guidelines for antiretroviral postexposure prophylaxis after sexual, injection drug use, or other nonoccupational exposure to HIV—United States, 2016. Center for Disease Control and Prevention; 2016; Available at: https://aidsinfo.nih.gov/guidelines. [Accessed 10 Feb 2019]
4. 4. Muller WJ, Chadwick EG. Pediatric considerations for postexposure Human Immunodeficiency Virus prophylaxis. Infect Dis Clin North Am 2018; 32:91–101.
5. Patel P, Borkowf CB, Brooks JT, et al. Estimating per-act HIV transmission risk: a systematic review. AIDS 2014; 28:1509–1519.
6. Kalapila AG, Marrazzo J. Antiretroviral therapy for prevention of Human Immunodeficiency Virus infection. Med Clin North Am 2016; 100:927–950.
7. 7.Malinverni S, Gennotte A-F, Schuster M, et al. Adherence to HIV post-exposure prophylaxis: A multivariate regression analysis of a 5 years prospective cohort. J Infect 2018; 76:78–85.
8. 8. Ford N, Irvine C, Shubber Z, et al. Adherence to HIV postexposure prophylaxis: a systematic review and meta-analysis. AIDS Lond Engl 2014;28:2721–2727.
9. Scannell M, Kim T, Guthrie BJ. A meta-analysis of HIV postexposure prophylaxis among sexually assaulted patients in the United States. J Assoc Nurses AIDS Care JANAC 2018; 29:60–69.

10.Schilling S, Deutsch SA, Gieseker R, et al. Improving HIV post-exposure prophylaxis rates after pediatric acute sexual assault. Child Abuse Negl 2017; 69:106–115.

11.Bogoch II, Scully EP, Zachary KC, et al. Patient attrition between the emergency department and clinic among individuals presenting for HIV nonoccupational postexposure prophylaxis. Clin Infect Dis Off Publ Infect Dis Soc Am 2014; 58:1618–1624

12. 12. Ford N, Venter F, Irvine C, et al. Starter packs versus full prescription of antiretroviral drugs for postexposure prophylaxis: A systematic review. Clin Infect Dis 2015;60(suppl 3):S182–6.
13. Jain S, Krakower DS, Mayer KH. The transition from postexposure prophylaxis to preexposure prophylaxis: An emerging opportunity for biobehavioral HIV prevention. Clin Infect Dis Off Publ Infect Dis Soc Am 2015; 60(Suppl 3):S200–S204.
14. Riddell J, Amico KR, Mayer KH. HIV preexposure prophylaxis: A review. JAMA 2018; 319:1261–1268.