PEP Care via Telemedicine

Post-Exposure Prophylaxis (PEP) Larry York, PharmD, BCIDP, BCPS, AAHIVP Sascha Bianchi, MPH Some slides adapted from John Leander Po, MD, PhD 1 Disclaimer "This presentation is supported by the Health Resources and Services Administration (HRSA) of the U.S. Department of Health and Human Services (HHS) as part of an award totaling $3,278,366. The contents are those of the author(s) and do not necessarily represent the official views of, nor an endorsement, by HRSA, HHS or the U.S. Government." The views and opinions expressed in this presentation are not necessarily those of the Pacific AIDS Education and Training Centers (PAETC), the Regents of the University of California or its San Francisco campus (UCSF or collectively, University) nor of our funder the Health Resources and Services Administration (HRSA). Neither PAETC, University, HRSA nor any of their officers, board members, agents, employees, students or volunteers make any warranty, express or implied, including the warranties of merchantability and fitness for a particular purpose; nor assume any legal liability or responsibility for the accuracy, completeness or usefulness of information [,apparatus, product] or process assessed or described; nor represent that its use would not infringe privately owned rights. 2 Objectives By the end of this discussion, you will be able to understand and discuss: 1. The research related to Post-Exposure Prophylaxis for HIV2. How to initiate and manage PEP care3. The PEP delivery methods via telemedicine 3 What is PEP? Regimen to reduce risk of contracting HIV if exposed "Plan B" of HIV 72 hour window of efficacy from moment of possible exposure Typically consists of Truvada 200/300 mg plus another agent Unlike PrEP, PEP is a complete antiretroviral regimen against HIV 4 HIV ACQUISITION RISK GROUPS 5 HIV Occupational PEP (oPEP) Exposures common 57 documented cases of health care workers contracting HIV from exposures as of 2010; No new documented cases since 1999 143 other possible cases (1981-2010) Area of considerable concern but little data Source: 6 HIV Non-Occupational PEP (nPEP) Includes all exposures outside of a healthcare setting Underutilized resource to potentially prevent HIV spread More difficult to obtain medicine 7 Which fluids are potentially infectious for HIV? blood? saliva? sweat? feces? semen? vaginal secretions? cerebrospinal fluid? breastmilk? synovial fluid? pleural fluid? peritoneal fluid? pericardial fluid? amniotic fluid? pus? urine? vomitus? 7 Which fluids are potentially infectious for HIV? blood saliva sweat feces semen vaginal secretions cerebrospinal fluid breastmilk synovial fluid pleural fluid peritoneal fluid pericardial fluid amniotic fluid pus urine vomitus 8 Exposure Risks (average, per episode, involving HIV-infected source patient) Exposure Risk Percutaneous (blood)1 0.3% Mucocutaneous (blood)2 0.09% Receptive anal intercourse3 1 - 2% Insertive anal intercourse4 0.06% Receptive vaginal intercourse5 0.1 0.2% Insertive vaginal intercourse6 0.03 0.14% Receptive oral (male)7 0.06% Female-female orogenital8 4 case reports IDU needle sharing9 0.67% Vertical (no prophylaxis)10 24% 9 10 1. Bell DM. Am J Med 1997;102(suppl 5B):9--15. 2. Ippolito G et al. Arch Int Med 1993;153:1451--8. 3. Am J Epidemiology 1999;150:306-11. 4. Am J Epidemiology 1999;150:306-11. 5. MMWR 47;RR-17, 1998. 6. NEJM 336(15):1072-8. (rates in Europe & U.S.) 7. Am J Epidemiology 1999;150:306-11. 8. Rothenberg RB et al. AIDS 1998;12:2095-2105. 9. MMWR 47;RR-17, 1998. 10. ACTG 076 Other Risk Factors to Consider Viral load of source patient Considerations for needlesticks: Glove use 50% decrease in volume of blood transmitted Hollow bore vs solid bore Large diameter needles weakly associated with increased risk Drying conditions Tenfold drop in infectivity every 9 hours 10 11 Efficacy of gloves in reducing blood volumes transferred during simulated needlestick injury.Mast ST, Woolwine JD, Gerberding JL.Department of Medicine and Infectious Diseases, University of California, San Francisco.This study was designed to evaluate factors that affect blood volumes transferred to skin during simulated needlestick injuries in an in vitro paper prefilter model and an ex vivo porcine tissue model. The effect of needle type and size, penetration depth, and glove use on the volume of radiolabeled blood transferred was determined in each model. Blood volumes ranged from 0.47 +/- 0.26 microL (30-gauge needle, 0.5-cm depth, in vitro model) to 5.88 +/- 1.45 microL (18-gauge needle, 2.0-cm depth, in vitro model). Needle size and penetration depth were significantly associated with transfer volume. Glove material reduced the transferred blood volume by 46%-86% in both models. Transfer volumes were within the same order of magnitude for all conditions. Hence, virus titer in the source blood may be a better predictor of needlestick infectivity than is exposure volume. Regardless, gloves may exert some protective effect and should be worn whenever needles are handled. HIV TESTING AND ACUTE HIV 12 Laboratory Markers of HIV Infection 13 13 HIV-1/HIV-2 antibody differentiation immunoassay (-) (+) HIV-1 (+) HIV-2 (-) HIV-1 antibodies detected HIV-1 (-) HIV-2 (+) HIV-2 antibodies detected HIV-1 (-) or indeterminate HIV-2 (-) NAT NAT (+) Acute HIV-1 infection NAT (-) Negative for HIV-1 Negative for HIV-1 and HIV-2 antibodies and p24 Ag HIV-1 (+) HIV-2 (+) HIV antibodies detected* *Additional testing required to rule out dual infection 4th generation HIV-1/2 immunoassay 14 14 Acute Retroviral Syndrome Signs/Symptoms Fever Malaise Myalgia Rash Headache Sore throat Lymphadenopathy 15 15 Acute Retroviral Syndrome Presentation Most patients who contract HIV are symptomatic with seroconversion1 Flu-like or mono-like illness often accompanied by a rash2 Onset typically 2-6 weeks following exposure, but high variability1 Treatment of acute HIV with antiretroviral therapy may have significant long-term benefit3 1. Schacker T et al. Ann Int Med 1996;125:257-64. 2. Kahn JO, Walker BD. N Engl J Med. 1998;339:33-39. 3. Walker B. State of the Art Lecture and Summary. 8th CROI, Session #37. 16 HIV RNA in Semen (Log10 copies/ml) Acute Infection 6 wks Asymptomatic Infection HIV Progression AIDS 2 3 4 5 1/1000 - 1/10,000 1/500 - 1/2000 1/100- 1/1000 1/30- 1/200 Cohen & Pilcher, J Infect Dis. 2005 Virus 75-750 times more infectious Increased Risk of Sexual Transmission of HIV 17 1/22/21 HIV: New Tests and New Algorithms 17 PEP ANTIRETROVIRALS ANDTHEIR MANAGEMENT 18 Key Points of PEP Regimens Duration is always 28 days COMPLETE regimen against HIV Timing is critical Begin AS SOON AS POSSIBLE 19 Preferred PEP Regimens Integrase-based regimens preferred: Truvada 200/300 mg + Isentress (raltegravir) 400 mg twice daily Truvada 200/300 mg + Tivicay (dolutegravir) 50 mg once daily Total duration is always 28 days 20 Truvada (FTC/TDF) Single pill containing two medications Emtricitabine (FTC) 200 mg Tenofovir disoproxil (TDF) 300 mg Can be taken with or without food Both agents have renal adjustments These adjustments have NOT been studied for PEP 21 Side Effects of Truvada May experience nausea, bloating upon initiation Usually resolves within 2-3 weeks Headache Increased risk of decreased renal function Uncommon but known adverse effect from TDF Renal function usually returns to normal if TDF stopped Increased risk of decreased bone mineral density 22 When NOT to use Truvada Do not begin Truvada if CrCl < 60 mL/min If CrCl declines to < 50 mL/min, alternative recommended Definite recommended point for renal dose adjustments 23 Truvada and Chronic HBV FTC and TDF both active against HBV Sudden withdrawal may lead to acute HBV flares Critical to know HBV status of PEP patient to assess risk May consider continuing Truvada or TDF beyond 4 week period Assess by reviewing HBsAb, HBcAb, HBsAg 24 Critical Issues in PEP Treatment Timing is key Efficacy decreases continuously after initial exposure Beyond 72 hours, PEP generally no longer recommended Treatment duration is 4 weeks If source patient has known HIV resistance: Optimize regimen to treat the resistant virus 25 NRTIsNucleoside/Nucleotide Reverse Transcriptase Inhibitors Indirectly inhibits enzyme required to copy viral RNA to DNA. 26 26 INSTIsIntegrase Inhibitors Inhibits strand transfer of viral DNA to host cell DNA by the integrase enzyme. 27 27 Side Effects of INSTI-Based PEP Increased incidence of headaches Sleep disturbance Insomnia more prevalent in drug studies 28 Isentress (RAL) Advantages Well-tolerated Data for use in pregnancy Very low risk of drug interactions Disadvantages Twice-daily dosing Lower barrier to HIV resistance 29 Tivicay (DTG) Advantages Well-tolerated Once-daily dosing Very high barrier to HIV resistance Disadvantages Neural tube defects? 30 Dolutegravir and Neural Tube Defects? Recent study from Botswana suggested this connection Has not been observed in studies or through US pregnancy registry Incidence of NTDs comparatively higher in Botswana More recent data from this study did not find a statistically significant increase in neural tube defects 31 Drug Interactions of INSTI-Based PEP RAL and DTG can chelate polyvalent cations and lose efficacy Give 2 hours before or 6 hours after Ca/Mg/Fe/Al/Zn supplements Not recommended with select anticonvulsants Phenytoin, phenobarbital, carbamazepine diminish INSTI levels DTG can increase metformin levels Monitor closely Consider metformin 1,000 mg/day max during duration 32 Alternative PEP Regimens For renal dysfunction/kidney disease (CrCl < 60 mL/min): Dose-adjusted lamivudine and zidovudine 300 mg twice daily Combivir includes both lamivudine and zidovudine at full dose Preferred 3rd agent (raltegravir, dolutegravir) For alternative to raltegravir or dolutegravir: Darunavir 800 mg daily + ritonavir 100 mg daily If pregnant, darunavir 600 mg + ritonavir 100 mg both twice daily Consult with specialist for further regimens Particularly if source patient has known resistance 33 Zidovudine Advantages Well-studied against HIV Disadvantages Twice-daily dosing Numerous adverse effects Tolerability concerns 34 PIsProtease Inhibitors Inhibits protease, the enzyme that cuts HIV protein into smaller strands used to assemble a new virus. 35 PIsProtease Inhibitors Inhibits protease, the enzyme that cuts HIV protein into smaller strands used to assemble a new virus. 36 Prezista (darunavir) + Norvir (ritonavir) Advantages Very high barrier to HIV resistance Better tolerated than other PIs Disadvantages At least two pills once daily Numerous drug interactions Metabolic/liver/lipid effects 37 Occupational PEP Testing Baseline: HIV screening Renal and hepatic function tests Complete blood count (CBC) Repeat renal/hepatic testing and CBC 2 weeks post-exposure Repeat HIV testing at 6 weeks, 12 weeks, and 6 months If 4th gen testing used, can retest at 6 weeks and 4 months 38 HBV/HCV Retesting Warranted at 4-6 months if source patient known or suspected to have either HBV or HCV Only retest HBV if susceptible at baseline Include HBsAb, HBcAb, HBsAg to fully assess status HCV/HIV coinfection may delay HIV antibody response If concerned, recheck both at 4-6 months 39 Non-Occupational PEP Testing Source: 40 nPEP Testing Footnotes Source: 41 Counseling at time of exposure and follow-up appointments Use condoms Avoid blood or tissue donations Avoid pregnancy & breastfeeding (if possible) Possible drug side effects Possible drug interactions Importance of adherence to PEP regimen Consider re-evaluation of exposed health care professional (HCP) 72 hours post-exposure, especially after additional information about the exposure or SP becomes available. 42 PEP in Pregnancy Considerations similar to those of non-pregnant exposed persons. The pregnant exposed person and her fetus are at risk for HIV acquisition. Most PEP regimens, benefits outweigh the risk of infant (and maternal) exposure to ARVs. Based on limited data, use of ARVs in pregnancy does not appear to increase the risk of birth defects compared to the general population. Toxicities from currently recommended PEP medicationsare not thought to be significantly increased in pregnancy. 43 43 PEP and Lactation Breastfeeding is not a contraindication for PEP. The decision to take PEP and/or continue breastfeeding is complex and individualized, and expert consultation is recommended Considerations: Acute HIV in a breastfeeding mother greatly increases the risk of HIV transmission to her infant. Pump and discard Pumping and storing while waiting on SP's HIV test results Limited data on PEP medications in breastmilk 44 o Tenofovir DF and emtricitabine (TDF and FTC, components of Truvada) and protease inhibitors can be detected in breastmilk only in very limited amountso Lamivudine (3TC, Epivir) can penetrate the breastmilk in significant amountso Raltegravir (RAL, Isentress)unknown extent of breastmilk penetration 44 Conclusion PEP a valuable resource that may be underutilized Well-tolerated agents available for use Efficiency in prescribing and taking PEP critical to success 45 Cheat Sheet Part 1 Preferred regimens: Truvada 200/300 mg daily + Tivicay 50 mg daily Or Truvada 200/300 mg daily + Isentress 400 mg BID CrCl < 60 mL/min regimens: Combivir 150/300 mg BID + an above INSTI May administer zidovudine and dose-adjusted lamivudine separately in place of Combivir Full-dose lamivudine safe down to as low as CrCl > 30 mL/min 46 Cheat Sheet Part 2 If pregnant: Truvada 200/300 mg daily + Isentress 400 mg BID Truvada 200/300 mg daily + Tivicay 50 mg daily If INSTI-intolerant: Truvada 200/300 mg daily + Prezista 800 mg daily + Norvir 100 mg daily If INSTI-intolerant and pregnant: Truvada 200/300 mg daily + Prezista 600 mg BID + Norvir 100 mg BID 47 PEP: Special Cases Known or suspected resistance of the source virus to antiretroviral agents Delayed exposure report (after 72 hours) Exposed person has serious illness (eg, renal disease) 48 49 PEP PATIENT NAVIGATION IN THE ERA OF COVID-19 50 PEP Navigation Process Overview Evaluating Provider PEP Clinic Initiate PEP within 72 hours. Conduct baseline testing. Ensure patient can access at least 3 days of medication. Ensure patient accesses remainder of medication. Follow-up within 1 week. Follow-up at 4-6 weeks. 51 Evaluating provider and PEP clinic may be the same. Or evaluating provider may be ED, urgent care, PCP, Health Department etc If possible (ED, Urgent care), initiate first dose, buys patient some time If possible. draw labs, easier to ensure it happens in a timely manner. No need to wait for results Get meds and follow up. Discuss in detail on next slides 51 Ensure patient can access at least 3 days of medication while setting up remainder Preplanned billing options in case of insurance issues Trusted pharmacies that have training on PEP Complete PAs, if needed, enroll in manufacturers' assistance 52 Copay Assistance/Free Medications Available! 53 Intake via Telemedicine Have a pre-planned process for collecting important information and communicating it with provider Have an assigned person that the patient/pharmacy can reach when problems arise Important messages should be repeated often due to trauma associated with PEP 54 Follow-up within 1 week Providers who understand the urgency and are willing to double book Multiple options for patients, video visit, phone visit, in-person Complete any missing baseline labs Ensure patients have access to full 28 days of medication 55 Follow-up Follow-up at 4-6 weeks Complete follow-up labs Transition to PrEP if patient desires Labs completed on day 25, PrEP started immediately on day 29 56 56 Additional Considerations in the Era of COVID-19 Emergency rooms are overwhelmed Preferable to directly see patients same day Schedule lab visits later in the day to avoid crowds Have mental health linkages to care on hand Work with pharmacies able to deliver medication Virtual Visits Patient Access: Telephone needed for phone consults Smartphone or computer with working camera needed for video consults Telemedicine Coordination: Confirm patient's appointment type Coordinate necessary lab work and access to virtual consults Make sure patient has a clear understanding of follow-up plan, provide in writing if possible Make sure patient has access to all necessary testing, including STI swabs Telemedicine Best Practices Tips for Coordinators: -Have a back-up plan if technology fails -Determine what information is necessary -Call patient ahead of time to practice using telehealth systems Tips for Providers: -Determine what information is necessary -Many additional services can be provided without requiring a face-to-face visit including vaccinations, STI treatments, emergency contraception Conclusion The practice of PEP is straightforward Supporting PEP management, however, can take considerable work Telemedicine a perfect avenue to deliver PEP care Research still ongoing in simplifying PEP management THANK YOU 61