Pr EParing the Community Pharmacist for PreExposure Prophylaxis

“Pr. EParing” the Community Pharmacist for Pre-Exposure Prophylaxis DAVID GLASER, PHARMD PGY 1 COMMUNITY PHARMACY RESIDENT SOUTHWEST CARE CENTER

Conflict of Interest Disclosure Statement • No potential or actual conflicts of interest

Learning Objectives Pharmacist objectives: • Review the burden of HIV disease and transmission in New Mexico • Understand who is at risk of obtaining HIV • Explain the indications for HIV Pre-Exposure Prophylaxis (Pr. EP) • Discuss efficacy of FDA approved options for Pr. EP • Be able to effectively counsel a patient receiving Pr. EP

Learning Objectives Pharmacy Technician objectives: • Describe indications for Pr. EP and appropriate candidates • Describe importance of keeping Pr. EP on shelf in pharmacies • Explain importance of on-time refills/pick up for patient's receiving Pr. EP

Human Immunodeficiency Virus (HIV) • Retrovirus (RNA → DNA) • Targets Immune System • T-Helper Cells/CD 4+ cells • Infected cells then become a factory for HIV • CD 4 cell dies • Lowers immune system function • Susceptible to opportunistic infections Source: USDOH AIDSinfo: aidsinfo. nih. gov

HIV Transmission Body fluids • Blood • Semen • Pre-seminal fluids • Rectal fluids • Vaginal fluids • Breast milk NOT via “casual contact” Source: USDOH AIDSinfo: aidsinfo. nih. gov

• Diagnosis rates decreased by 11% from 2010 to 2017 • Not evenly distributed • The Southern US accounted for 52% of new HIV diagnoses Image Source: United States Centers for Disease Control - https: //www. cdc. gov/hiv/images/statistics/overview/geography/hiv-us-map-2017. png CDC. Diagnoses of HIV infection in the United States and dependent areas, 2017 HIV Surveillance Report 2018; 29

CDC. Diagnoses of HIV infection in the United States and dependent areas, 2017 HIV Surveillance Report 2018; 29

HIV in New Mexico 2017 -18 New Mexico Demographics & Incidence Race/Ethnicity Number Rate per 100, 000 Hispanic/Latino 1654 203. 9 White 1189 169. 3 American Indian/Alaska Native 280 188. 6 Black/African American 196 605. 0 Multiple Races 95 428. 1 Asian 12 42. 9 Native Hawaiian/Other Pacific islander 1 83. 8 • In 2017, approximately 3, 427 people were living with HIV in New Mexico • Rates of newly diagnosed HIV in New Mexico are down from 2017 compared to 2018 • Incidence of 7. 8 to 6. 9 per 100, 000 people • Why are these rates declining? CDC. HIV Surveillance Report 2018; Diagnoses of HIV Infection in the United States and Dependent Areas, 2018 (Preliminary). Vol. 30

CDC. National Center for HIV/AIDS, Viral Hepatitis, STD, and Tb Prevention. Selected National HIV Prevention and Care Outcomes, 2016

CDC. National Center for HIV/AIDS, Viral Hepatitis, STD, and Tb Prevention. Selected National HIV Prevention and Care Outcomes, 2016

CDC. National Center for HIV/AIDS, Viral Hepatitis, STD, and Tb Prevention. Selected National HIV Prevention and Care Outcomes, 2016

World AIDS Day • Annually on December 1 st

What Determines Your Risk For HIV? • Sexual orientation • Gender/sex identity • Drug use • Race • Age • Geographic location • Occupation

Average Risk of HIV Transmission Per Exposure to Infected Source Percentage Odds of Acquiring Infection Non-Sexual Modes Blood Transfusion 90% 9 in 10 Needle Sharing 0. 67% 1 in 149 Needle Stick 0. 30% 1 in 333 Vaginal Sex Risk to female if male is HIV-positive: High Income Countries/Low Income Countries 0. 08% / 0. 30% 1 in 1250 / 1 in 333 0. 04% / 0. 38% 1 in 2500 / 1 in 263 Risk to male if female is HIV-positive: High Income Countries/Low Income Countries Anal Sex Receptive partner’s risk (w/ ejaculation) 1. 43% 1 in 70 Receptive partner’s risk (w/o ejaculation) 0. 65% 1 in 154 Insertive partner’s risk (uncircumcised) 0. 62% 1 in 161 Insertive partner’s risk (circumcised) 0. 37% 1 in 270 Heads or Tails: Risk of HIV acquisition chart. POZ April/May 2014. CDM Publishing, LLC.

Risk Factor Modifiers INCREASE YOUR HIV RISK 1 DECREASE YOUR HIV RISK • Contact with someone in the acute stage HIV infection (26 x) • Undetectable = Untransmissible (U=U) (100%)2 • Co-infection with a sexually transmitted infection (STI) (8 x) • Intimate partner violence (1. 5 x) • Pre-exposure prophylaxis (Pr. EP) (96% - 99%) • i. Pre. X study – Increased protective rates up from 44% to 96% at a minimum of 4 doses weekly • Post-Exposure Prophylaxis (PEP) – Similar to Pr. EP 3 • Proper condom use (80%) • Circumcision 4 1. Heads or Tails: Risk of HIV acquisition chart. POZ April/May 2014. CDM Publishing, LLC. 2. Rodger AJ, Cambiano V, Bruun T, et al. Risk of HIV transmission through condomless sex in serodifferent gay couples with the HIV-positive partner taking suppressive antiretroviral therapy (PARTNER 2): final results of a multicentre, prospective, observational study. Lancet. 2019; 393: 2428 -38. 3. Centers for Disease Control and Prevention: U. S. Department of Health and Human Services. Updated Guidelines for Antiretroviral Postexposure Prophylaxis After Sexual, Injection Drug Use, and Other Nonoccupational Exposure to HIV—United States, 2016. 4. Siegfried N, Muller M, Deeks J, et al. HIV and male circumcision--a systematic review with assessment of the quality of studies. Lancet Infect Dis 2005; 5: 165.

What is Pr. EP?

Pr. EP • Daily pill to prevent HIV • First FDA approved in July 2012 • Does NOT prevent STI’s Image Source: University of Washington HIV Curriculum – Section 5, Topic 5: Pre-Exposure Prophylaxis. Figure 2. https: //www. hiv. uw. edu/go/prevention/preexposure-prophylaxis-prep/core-concept/all

Guideline Recommendations MEETS ALL OF THE FOLLOWING: AND MEETS ONE OF THE FOLLOWING: • An adult or adolescent weighing ≥ 35 kg (~77 lbs) • Has sex with both women and men • HIV negative • Infrequent condom use • Is in a relationship with an HIV • Sexual contact in the last 6 months positive partner • Not participating in a monogamous • Diagnosed or reported STI in the relationship with a recently tested last 6 months HIV negative partner CDC Recommendation: May also consider transactional sex workers, high number of sex partners, and/or in high prevalence HIV area or network. 1. (CDC), US Public Health Service. Preexposure Prophylaxis for the Prevention of HIV Infection in the United States— 2017 Update: A Clinical Practice Guideline. 2. US Preventive Services Task Force, Owens DK, Davidson KW, et al. Preexposure Prophylaxis for the Prevention of HIV Infection: US Preventive Services Task Force Recommendation Statement. JAMA. 2019; 321: 2203 -13.

Who is a Candidate for Pr. EP? People who: Evaluate individual patient needs • Have condomless sex • Uncertainty of partner’s status • Multiple sex partners • Anal sex • Having an HIV-positive partner • Transactional sex / commercial sex work • Ease of mind or security • Potential for risk in the future • Occupational risk • Medical professionals • Law enforcement 1. (CDC), US Public Health Service. Preexposure Prophylaxis for the Prevention of HIV Infection in the United States— 2017 Update: A Clinical Practice Guideline. 2. US Preventive Services Task Force, Owens DK, Davidson KW, et al. Preexposure Prophylaxis for the Prevention of HIV Infection: US Preventive Services Task Force Recommendation Statement. JAMA. 2019; 321: 2203 -13.

People who inject drugs (PWID) • Shared use of drug injection equipment • Any risks of sexual HIV acquisition • IV, skin popping, etc. Should also consider: • Hormone injections • Unprofessional tattoos • Vampire facials 1. (CDC), US Public Health Service. Preexposure Prophylaxis for the Prevention of HIV Infection in the United States— 2017 Update: A Clinical Practice Guideline. 2. US Preventive Services Task Force, Owens DK, Davidson KW, et al. Preexposure Prophylaxis for the Prevention of HIV Infection: US Preventive Services Task Force Recommendation Statement. JAMA. 2019; 321: 2203 -13.

Risk Assessment: In the Past 6 Months: 1. Do you have sex with men, women, or both? How often are condoms being used? 2. Have you had an STI in the last 6 months? 3. Are any of your partners HIV positive? (If any are HIV+) How many times did you have sex without a condom? 4. Have you used any substances? (If yes) Which substances did you use and via what route? 1. (CDC), US Public Health Service. Preexposure Prophylaxis for the Prevention of HIV Infection in the United States— 2017 Update: A Clinical Practice Guideline. 2. US Preventive Services Task Force, Owens DK, Davidson KW, et al. Preexposure Prophylaxis for the Prevention of HIV Infection: US Preventive Services Task Force Recommendation Statement. JAMA. 2019; 321: 2203 -13.

Image Source: University of Washington HIV Curriculum – Section 5, Topic 5: Pre-Exposure Prophylaxis. Figure 6. https: //www. hiv. uw. edu/go/prevention/preexposure-prophylaxis-prep/core-concept/all

My Recommendation for Baseline Labs HIV 1+2 Ab and Ag - negative Hepatitis A & B Serologies (A- s. Ab; B- s. Ab, c. Ab, s. Ag) Hepatitis C Antibody – consider every 6 months Comprehensive Metabolic Panel STI Screening - provide condoms if possible! Pregnancy test - assigned females at birth of child-bearing potential 1. (CDC), US Public Health Service. Preexposure Prophylaxis for the Prevention of HIV Infection in the United States— 2017 Update: A Clinical Practice Guideline. 2. US Preventive Services Task Force, Owens DK, Davidson KW, et al. Preexposure Prophylaxis for the Prevention of HIV Infection: US Preventive Services Task Force Recommendation Statement. JAMA. 2019; 321: 2203 -13.

FDA-Approved Pharmacologic Therapy Truvada® Image Source: Pr. EP Access Now. https: //www. pan. org. au/blog/2018/11/23/descovy-as-prep Descovy®

Mechanism of Action Tenofovir and Emtricitabine • Two Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTI’s) emtricitabine and tenofovir • Inhibits the reverse transcriptase enzyme • Competes with nucleosides/nucleotides into the elongating strand during reverse transcription Image Source: University of Washington HIV Curriculum – Section 3, Topic 1: Antiretroviral Medications and Initial Therapy. . Figure 1. https: //www. hiv. uw. edu/go/antiretroviral-therapy/general-information/core-concept/all

Tenofovir disoproxil fumarate (TDF) vs. Tenofovir alafenamide (TAF) • TDF phosphorylated outside of the cell • 0. 4 min t½ in plasma • Phosphorylated in plasma (extracellularly) • Only this version gets into the cell • Of 300 mg dose, ~30 mg makes it into cell • TAF phosphorylated inside of the cell Image source: Spinner CD, Brunetta J, Shalit P, et al. DISCOVER study for HIV Pre-Exposure Prophylaxis: F/TAF has a more Rapid Onset and Longer Sustained Duration of HIV protection compared to F/TDF[Presentation] Paper presented at: IAS 2019; 21 -24 July, 2019; Mexico City, Mexico. • 30 min t½ in plasma • Phosphorylated intracellularly • Does not have to be phosphorylated to be taken into the cell • Of 25 mg dose, ~22. 5 mg makes it into cell

Truvada® (FTC/TDF) emtricitabine/tenofovir disoproxil fumarate (200 mg/300 mg) • Indicated for HIV-negative atrisk adults/adolescents who weigh at least 35 kg (~77 lbs) • Dose: 1 tablet by mouth once daily with or without food Kidney Function • Cr. Cl <60 m. L/minute: Use is not recommended • Nephrotoxicity/Fanconi Syndrome Side effects: • Decreased bone mineral density (13%) • Headache (7%) • Abdominal Pain (4%) • Weight Loss (3%) Drug interactions: • Harvoni® (ledipasvir/sofosbuvir) • Nephrotoxic agents Gilead Sciences Inc. TRUVADA tablets for oral use, U. S. Prescribing information, FDA. Foster City, CA.

Truvada® Boxed Warnings • Can ONLY be used in individuals confirmed to be HIV-negative • Risk of drug resistance • Monitor hepatic function closely in Hep B infected individuals • Discontinuation → Hep B exacerbation → Fulminant Hepatitis → Death Gilead Sciences Inc. TRUVADA tablets for oral use, U. S. Prescribing information, FDA. Foster City, CA.

Descovy® (FTC/TAF) emtricitabine/tenofovir alafenamide (200 mg/25 mg) • Indicated for HIV-negative at-risk adults/adolescents who weigh at least 35 kg (~77 lbs) • Dose: 1 tablet by mouth once daily with or without food Kidney Function • Cr. Cl <30 m. L/minute: Use is not recommended Side effects: • Nausea (10%) • Diarrhea, Nausea, headache, fatigue, abdominal pain (≥ 2%) Drug interactions: • P-glycoprotein (P-gp) inducers • Nephrotoxic agents NOT indicated for those at risk from receptive vaginal sex Gilead Sciences Inc. DESCOVY tablets for oral use, U. S. Prescribing information, FDA. Foster City, CA.

Descovy® Boxed Warnings • Can ONLY be used in individuals confirmed to be HIV-negative • Risk of drug resistance • Monitor hepatic function closely in HBV infected individuals • Discontinuation → Hep B exacerbation → Fulminant Hepatitis → Death Gilead Sciences Inc. DESCOVY tablets for oral use, U. S. Prescribing information, FDA. Foster City, CA.

Pr. EP Counseling - FAQs “How long do I have to take Truvada® or Descovy® before I’m fully protected? ”

International AIDS Society (IAS) 2019 A More Rapid Onset and Longer Sustained Duration of HIV Protection seen in Descovy® vs Truvada® Spinner, et al. • 4 weeks: 6. 3 fold higher concentrations in FTC/TAF vs FTC/TDF • 98% of FTC/TAF patients had drug levels at or above the protective threshold at 20 -28 hours post dose • Only 68% of FTC/TDF • FTC/TAF steady state after last dose: ~16 days • FTC/TDF ~10 days • Can be inferred that FTC/TAF reaches effective concentrations faster • Also remains at effective concentrations in the target cell for much longer than FTC/TDF However, this data and its correlation to HIV Pr. EP is unknown. Spinner CD, Brunetta J, Shalit P, et al. DISCOVER study for HIV Pre-Exposure Prophylaxis: F/TAF has a more Rapid Onset and Longer Sustained Duration of HIV protection compared to F/TDF[Presentation] Paper presented at: IAS 2019; 21 -24 July, 2019; Mexico City, Mexico.

Pr. EP Counseling - FAQs “How long do I have to take Truvada® or Descovy® before I’m fully protected? ” “We don’t know for sure, but from the studies, it seems that it will take 7 days for rectal tissue to be protected, and about 3 weeks for vaginal tissue and blood to be fully protected. You should use condoms and clean needles/supplies during this time. ” 1. Seifert SM, Glidden DV, Meditz AL, et al. Dose response for starting and stopping HIV preexposure prophylaxis for men who have sex with men. Clin Infect Dis. 2015; 60: 804 -10. 2. Anderson PL, Kiser JJ, Gardner EM, Rower JE, Meditz A, Grant RM. Pharmacological considerations for tenofovir and emtricitabine to prevent HIV infection. J Antimicrob Chemother. 2011; 66: 240 -50. 3. Patterson KB, Prince HA, Kraft E, et al. Penetration of tenofovir and emtricitabine in mucosal tissues: implications for prevention of HIV-1 transmission. Sci Transl Med. 2011; 3: 112 re 4.

Pr. EP Counseling - FAQs “Are Descovy® and Truvada® equally effective? ”

DISCOVER Trial • Descovy® for Pr. EP was non-inferior to Truvada® at 96 weeks • Treatment outcomes consistent across subgroups • Stressing adherence is key! US National Library of Medicine. Clinical trials website. Safety and efficacy of emtricitabine and tenofovir alafenamide (F/TAF) fixed-dose combination once daily for pre-exposure prophylaxis in men and transgender women who have sex with men and are at risk of HIV-1 infection (DISCOVER). Accessed 1/10/19

Pr. EP Counseling - FAQs “Are Descovy and Truvada equally effective? ” “Yes, studies showed that 99% of people on either medication remained HIV-free when they took it every day, with no missed doses. ” Spinner CD, Brunetta J, Shalit P, et al. DISCOVER study for HIV Pre-Exposure Prophylaxis: F/TAF has a more Rapid Onset and Longer Sustained Duration of HIV protection compared to F/TDF[Presentation] Paper presented at: IAS 2019; 21 -24 July, 2019; Mexico City, Mexico.

Adherence Tips for Pharmacies • Keep Truvada® and Descovy® on the shelf • Encourage auto-fill • 7 -day return-to-stock call lists • Encourage text/call/e-mail alerts • Encourage med-sync

Pr. EP Counseling - FAQs “I heard Truvada® can harm my bones and kidneys. Is this true? ”

Kidney Safety Outcomes Descovy® favorable in: • Estimated glomerular filtration rate (e. GFR) • Markers of proximal tubular function • Proteinuria was less common (24% vs 21%) • Drug-related kidney events (14 vs 26 cases) Mills, Workowski K, Campbell T et al/ Renal outcomes for participants Taking F/TAF vs FTDF for HIV Pr. EP in the DISCOVER trial: Presented at ID week; 5 th of October, 2019; Washington, D. C.

Bone Safety Outcomes Descovy® favorable in: • Spine and hip Bone Mineral Density (BMD) differences (all age groups) • BMD growth seen with Descovy® • Spine = mean % change from baseline (+0. 50 vs -1. 12), P<0. 001 • Hip = (+0. 18 vs -0. 99) P<0. 001 • Younger participants (<25 y/o) Wohl, DA, Ruan. PJ, Hosek S, et. Al. Bone safety outcomes with F/TAF vs. F/TDF for Pr. EP in the DISCOVER trial. Paper presented at: IDWeek 2019 02 -06 October 2019; Washington DC

Pr. EP Counseling - FAQs “I heard Truvada® can harm my bones and kidneys. Is this true? ” “Recent studies showed that Descovy® is safer on bones and kidneys, especially in your age group. At your next follow up visit with your provider, ask them if switching to Descovy® would be appropriate for you. ” 1. Mills, Workowski K, Campbell T et al/ Renal outcomes for participants Taking F/TAF vs FTDF for HIV Pr. EP in the DISCOVER trial: Presented at ID week; 5 th of October, 2019; Washington, D. C. 2. Wohl, DA, Ruan. PJ, Hosek S, et. Al. Bone safety outcomes with F/TAF vs. F/TDF for Pr. EP in the DISCOVER trial. Paper presented at: IDWeek 2019 02 -06 October 2019; Washington DC

Pr. EP Counseling - FAQs “I have a hard time remembering to take Pr. EP every day. Can I take my Pr. EP ‘on-demand’ instead of daily? ”

On-Demand Pre-Exposure Prophylaxis IPERGAY Study and the “ 2 -1 -1” Schedule • N=400 • 199 in FTC/TDF arm • 201 in placebo • 16 total new HIV diagnoses • 2 in FTC/TDF arm acquired HIV vs. 14 in placebo group • Not an FDA-approved indication • Only studied in men • Have to plan sex 24 hours ahead Image source: https: //www. pan. org. au/blog/2018/11/28/do-i-need-to-take-prep-every-day Molina JM, Capitant C, Spire B, et al. On-demand preexposure prophylaxis in men at high risk for HIV-1 infection. N Engl J Med. 2015; 373(23): 2237– 46.

Pr. EP Counseling - FAQs “I have a hard time remembering to take Pr. EP every day. Can I take my Pr. EP ‘on-demand’ instead of daily? ” Certain studies have shown that this works, however it was studied using Truvada®. It is not an FDAapproved dose, and effectiveness needs to be more closely studied in both Pr. EP medications. You are best protected by taking this medication every day, and doing your best to not miss doses. Try to form a routine around taking the medication to help with this. ” Molina JM, Capitant C, Spire B, et al. On-demand preexposure prophylaxis in men at high risk for HIV-1 infection. N Engl J Med. 2015; 373(23): 2237– 46.

Key Points • Pr. EP is for people who are HIV negative • Part of a complete HIV regimen, not the whole regimen • The maximum days supply for a Pr. EP prescription is 90 days • 30 d/s +2 rf’s, 90 d/s +0 rf’s • Pay attention to patient-specific needs • Truvada® vs Descovy® appropriateness • Indications, contraindications, boxed warnings, drug interactions • Be open and approachable! • We’re here to help our patients • Stress adherence! • Keep medication in stock and available for patients

Useful Resources - Pharmacists • Gilead (Truvada® and Descovy®) • Insured: • Co-Pay Cards - gileadadvancingaccess. com/copay-coupon-card • Co-pay coverage up to $7, 200 annually • Uninsured: • Advancing Access - gileadadvancingaccess. com/financial-support/uninsured • 400% above federal poverty level (household of 1 = $51, 040 annually) • Patient Advocacy Foundation • Medicare: • Co-pay coverage up to $7, 500 annually • patientadvocate. org • 400% above federal poverty level • nmhivguide. org The poverty guidelines updated periodically in the Federal Register by the U. S. Department of Health and Human Services under the authority of 42 U. S. C. 9902(2).

Useful Resources - Patients • Find a Pr. EP provider: • pleaseprepme. org • hiveonline. org (also includes HIV providers) • Blog to hear other experiences starting Pr. EP: • myprepexperience. blogspot. com • Syringe exchange, Narcan, DOH locations, etc: • nmhivguide. org • How to check if your insurance covers either Truvada® or Descovy®: • nastad. checkbookhealth. org

References 1. CDC. Diagnoses of HIV infection in the United States and dependent areas, 2017 HIV Surveillance Report 2018; 29. 2. CDC. HIV Surveillance Report 2018; Diagnoses of HIV Infection in the United States and Dependent Areas, 2018 (Preliminary). Vol. 30 3. CDC. National Center for HIV/AIDS, Viral Hepatitis, STD, and Tb Prevention. Selected National HIV Prevention and Care Outcomes, 2016 4. CDC. HIV Surveillance Supplemental Report 2018; 23(No. 1). 2018. 5. NM DOH HIV Surveillance and Epidemiology 2016 Annual Report 6. Heads or Tails: Risk of HIV acquisition chart. POZ April/May 2014. CDM Publishing, LLC 7. Miller WC, Rosenberg NE, Rutstein SE, Powers KA. Role of acute and early HIV infection in the sexual transmission of HIV. Curr Opin HIV AIDS. 2010; 5(4): 277– 282. doi: 10. 1097/COH. 0 b 013 e 32833 a 0 d 3 a 8. Galvin, S. , Cohen, M. The role of sexually transmitted diseases in HIV transmission. Nat Rev Microbiol 2, 33– 42 (2004) doi: 10. 1038/nrmicro 794 9. Jin F et al. Per-Contact Probability of HIV Transmission in Homosexual Men in Sydney in the Era of HAART. AIDS, published online ahead of print, 2010. Rodger AJ, Cambiano V, Bruun T, et al. Risk of HIV transmission through condomless sex in serodifferent gay couples with the HIV-positive partner taking suppressive antiretroviral therapy (PARTNER): final results of a multicentre, prospective, observational study. Lancet. 2019; 393: 2428 -38. 11. Harris NS, Johnson AS, Huang YA, et al. Vital Signs: Status of Human Immunodeficiency Virus Testing, Viral Suppression, and HIV Preexposure Prophylaxis - United States, 2013 -2018. MMWR Morb Mortal Wkly Rep. 2019; 68: 1117 -23. 12. Centers for Disease Control and Prevention: U. S. Department of Health and Human Services. Updated Guidelines for Antiretroviral Postexposure Prophylaxis After Sexual, Injection Drug Use, and Other Nonoccupational Exposure to HIV—United States, 2016. 13. Siegfried N, Muller M, Deeks J, et al. HIV and male circumcision--a systematic review with assessment of the quality of studies. Lancet Infect Dis 2005; 5: 165. 14. (CDC), US Public Health Service. Preexposure Prophylaxis for the Prevention of HIV Infection in the United States— 2017 Update: A Clinical Practice Guideline. 15. US Preventive Services Task Force, Owens DK, Davidson KW, et al. Preexposure Prophylaxis for the Prevention of HIV Infection: US Preventive Services Task Force Recommendation Statement. JAMA. 2019; 321: 2203 -13. 16. Gilead Sciences Inc. TRUVADA tablets for oral use, U. S. Prescribing information, FDA. Foster City, CA. 17. Gilead Sciences Inc. DESCOVY tablets for oral use, U. S. Prescribing information, FDA. Foster City, CA. 18. US National Library of Medicine. Clinical trials website. Safety and efficacy of emtricitabine and tenofovir alafenamide (F/TAF) fixed-dose combination once daily for pre-exposure prophylaxis in men and transgender women who have sex with men and are at risk of HIV-1 infection (DISCOVER). Accessed 1/10/19 19. Seifert SM, Glidden DV, Meditz AL, et al. Dose response for starting and stopping HIV preexposure prophylaxis for men who have sex with men. Clin Infect Dis. 2015; 60: 804 -10. 20. Anderson PL, Kiser JJ, Gardner EM, Rower JE, Meditz A, Grant RM. Pharmacological considerations for tenofovir and emtricitabine to prevent HIV infection. J Antimicrob Chemother. 2011; 66: 240 -50. 21. Patterson KB, Prince HA, Kraft E, et al. Penetration of tenofovir and emtricitabine in mucosal tissues: implications for prevention of HIV-1 transmission. Sci Transl Med. 2011; 3: 112 re 4. 22. Spinner CD, Brunetta J, Shalit P, et al. DISCOVER study for HIV Pre-Exposure Prophylaxis: F/TAF has a more Rapid Onset and Longer Sustained Duration of HIV protection compared to F/TDF[Presentation] Paper presented at: IAS 2019; 21 -24 July, 2019; Mexico City, Mexico. 23. Mills, Workowski K, Campbell T et al/ Renal outcomes for participants Taking F/TAF vs FTDF for HIV Pr. EP in the DISCOVER trial: Presented at ID week; 5 th of October, 2019; Washington, D. C. 24. Wohl, DA, Ruan. PJ, Hosek S, et. Al. Bone safety outcomes with F/TAF vs. F/TDF for Pr. EP in the DISCOVER trial. Paper presented at: IDWeek 2019 02 -06 October 2019; Washington DC 25. Molina JM, Capitant C, Spire B, et al. On-demand preexposure prophylaxis in men at high risk for HIV-1 infection. N Engl J Med. 2015; 373(23): 2237– 46. 26. The poverty guidelines updated periodically in the Federal Register by the U. S. Department of Health and Human Services under the authority of 42 U. S. C. 9902(2).