HIV. The Role of Pre-Exposure Prophylaxis (PrEP) for the Prevention of HIV. Brief History of HIV AIDS. Global HIV Infection.

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1 The Role of Pre-Exposure Prophylaxis (PrEP) for the Prevention of HIV HIV Sarah Kemink, PharmD, AAHIVP WMSHP Spring Seminar 5/05/2015 AIDS CD4 less than 200 +/- AIDS-defining illness Most common: Candidiasis of esophagus, bronchi, trachea, or lungs Pneumocystis jiroveci pneumonia Cytomegalovirus Mycobacterium avium Mycobacterium tuberculosis Toxoplasmosis Brief History of HIV Late 1970 s 1996 Fear, death, misinformation, outrage, civil disobedience Focus on hospice care/treating opportunistic infections 1996 present Combination treatment for HIV Disease became chronic, manageable disease Focus on compliance and managing adverse effects Global HIV Infection Global HIV Trends More than 34 million people worldwide living with HIV Annual AIDS-related mortality Decreased from peak of 2.2 million in mid-2000s to 1.7 million in 2011 Estimated 2.5 million deaths averted since 1995 due to ART Only 8 million people with ART coverage UNAIDS. World AIDS Day Report UNAIDS. World AIDS Day Report

2 Rates of New Infections Decreasing Sub-Saharan Africa, Asia, Oceania Increasing Eastern Europe, Central Asia, Middle East, North Africa Stable Latin America, North America, Western and Central Europe Transmission Unprotected sex between men who have sex with men (MSM) Unprotected transactional sex in commercial sex workers (CSW) Sharing of contaminated needle-injecting equipment UNAIDS. World AIDS Day Report UNAIDS. World AIDS Day Report HIV in the United States New HIV Infections Approximately 1.2 million people with HIV/AIDS Estimated 1 in 6 are undiagnosed Approximately 50,000 new infections yearly New HIV infections MSM account for ~60% of new cases of HIV in US Heterosexuals account for ~18% of all new HIV infections but >80% of new cases in women CDC. HIV Surveillance Supplemental Report CDC. HIV Surveillance Supplemental Report Rates of New Infection Stable incidence Increasing among specific communities African Americans Hispanics and Latinos MSM Injection drug users (IDUs) HIV Transmission Risk Risk per 10,000 Exposures Blood Transfusion (9,250) Receptive Anal Sex (138) Needle-sharing During IV Drug Use (63) Needle Stick (23) Insertive Anal Intercourse (11) Receptive Penile-Vaginal Intercourse (8) Insertive Penile-Vaginal Intercourse (4) Receptive Oral Intercourse (low) Insertive Oral Intercourse (low) Biting/Spitting (negligible) CDC. HIV Surveillance Supplemental Report CDC. Transmission Risk HIV Policies and the Law

3 HIV Prevention Behavioral Interventions Education/Counseling Screening for Behavioral Risk Factors Number/sex of partners HIV status of partners Types of sexual activities Barriers to abstinence Condom use Male Circumcision Screening and Treatment of STI s Treatment as Prevention HTPN 052 Perinatal Prophylaxis Use of ART to prevent HIV transmission from mother-to-child Incidence reduced by 40% 570,000 in ,000 in 2011 Cohen, et al. NEJM 2011; 365: UNAIDS. World AIDS Day Report Post Exposure Prophylaxis (PEP) Use of ART after exposure accidental needlestick sexual assault Not as effective as prevention of HIV transmission by avoiding exposures Less likely to be effective if initiated >72 hours after exposure Not likely to benefit persons with frequent, repeated exposures Pre-Exposure Prophylaxis (PrEP) Temporary Prevention of HIV during periods of high-risk behaviors Limit infected cells below a theoretical threshold under which infection cannot be established Block viral replication to allow host responses to clear infection Kuhar, et al. Inf Control 2013; 34(9):

4 Ideal PrEP Medication High potency against HIV Simple dosing schedule Low rates of adverse events Low frequency of drug-induced resistance High genital and rectal tissue concentrations Active in resting CD4 cells and during preintegration phase PrEP Options Tenofovir (Viread) Available as oral tablet or 1% vaginal gel Tenofovir disoproxil fumarate(tdf)/ Emtricitabine (ETV) (Truvada) Available as oral tablet Derdelinckxl, et al. PLoS Med. 2006; 3(11): e454 TDF/FTC (Truvada) Nucleotide/nucleoside reverse transcriptase inhibitors (NRTI s) Long intracellular half-lives High genital tissue concentrations Active in both active and resting CD4 cells Few drug interactions Both components active against Hepatitis B TDF/FTC (Truvada) Common adverse events: GI, tiredness, headache Typically short-term and mild Rare adverse events: Lactic acidosis rare case reports Renal dysfunction Acute risk = 1 4% Decrease bone mineral density 3-4% decline Truvada [package insert]. Foster City, CA; Gilead Sciences, Inc; 2013 Truvada [package insert]. Foster City, CA; Gilead Sciences, Inc; 2013 TDF/FTC Resistance FTC resistance TDF resistance M184V K65R Rapidly selected (within 15 May take up to 28 days days) Less likely if taking TDF/FTC Comparative effectiveness of current HIV prevention strategies Hurt, et al. Clin Inf Dis 2011; 53(12): Karim, et al. Lancet 2011; 378: e23-5 4

5 FEM-PrEP 2,120 women in Africa Trial stopped early for futility Compliance Self-reported adherence: 95% Pill counts: 88% Drug level testing: drug detected in < 40% participants High pregnancy rates in women on oral contraceptives Patient motivation is crucial! 70% perceived themselves to be at no or low risk for HIV infection TDF2 1,219 heterosexual participants in Africa 62% overall efficacy 49% in females, 80% in males Compliance Self-reported: 84% Significantly lower serum drug levels in infected participants vs. noninfected Van Damme, et al. NEJM 2012; 367(5): Thigpen, et al. NEJM 2012; 367(5): Partners PrEP 4758 heterosexual HIV serodiscordant couples in Africa 66% efficacy in women, 84% efficacy in men Compliance Pill counts: 97% Drug level testing: Infected participants: <30% had detectable levels of TDF/FTC Uninfected participants: >80 % had detectable levels of TDF/FTC iprex 2,499 MSM, transgender women in 11 sites (US, South America, Africa, Thailand) 44% reduction in HIV Infection Rate Compliance Pill use > 50% = risk reduction by 50% Pill use > 90 % = risk reduction by 73% Case control study 92% reduction with detectable levels of TDF Baeten, et al. NEJM 2012; 367(5): Grant, et al. NEJM 2010; 363(27): iprex OLE CDC PrEP Guidelines Grant, et al. Lancet Inf Dis 2014; 14:

6 PrEP Eligibility Risk Determination HIV NEGATIVE patients Serodiscordant couples High Risk MSM High Risk Heterosexual Men/Women High Risk Injection Drug Users (IDU) Pre-Treatment Testing HIV negative test result Rule out acute HIV infection Normal renal function (serum creatinine) Documented Hepatitis B infection or vaccination status Bacterial STI testing Gonorrhea Chlamydia Syphillis HIV Testing Western Blot No longer recommended 2 nd /3 rd Generation Antibody May miss acute HIV infection HIV RNA (Viral Load) Not covered by many insurance plans unless HIV antibody positive 4 th Generation Antigen/Antibody Testing (p24 Antigen) Recommended per updated CDC guidelines in 2014 Not widely available Action for Aids

7 Prescribing PrEP TDF/FTC (Truvada) One tablet daily 90 day prescription only Renew every 3 months ONLY after negative HIV test + compliance assessment Patient Counseling/Education Sexual risk reduction counseling Medication education Adherence counseling Provide condoms Baseline Compliance Follow-up and Monitoring Every 3 months: HIV Test Adherence Counseling Behavioral Risk Reduction Support Adverse Event Assessment STI Symptom Assessment Pregnancy Test (if appropriate) Ongoing Compliance Ongoing Compliance Every 3 months Evaluate current medication list for interactions Ongoing compliance assessment 7

8 Follow-up and Monitoring Every 6 months: Assess Renal Function Metabolic panel Urinalysis Test for Bacterial STI s Patient Stigma Patient Motivation PrEP Barriers Lack of Access/Cost of Treatment Insured/Uninsured Copay/Deductible Cost Stigma Primarily within/among/against the gay community PrEP is only for people who are promiscuous PrEP will lead to increased risky behaviors such as decreased condom use Condom Use and PrEP 70-80% efficacy in preventing HIV CDC study in 2013 showed declining condom use among gay men prior to PrEP (48% in 2005, 57% in 2011) iprex No change in condom use if patients thought they were on placebo vs. treatment Both iprex and Partners PrEP found DECREASING risk behavior over time CDC. MMWR 2013; 62(47): Grant, et al. NEJM 2010; 363(27): Baeten, et al. NEJM 2012; 367(5): Patient Stigma Patient Motivation PrEP Barriers Lack of Access/Cost of Treatment Insured/Uninsured Copay/Deductible Cost Patient Motivation Unwillingness to take pill daily Fear of side effects Lack of perceived risk False belief that HIV is an older generation s issue Avoiding sexual partners with known HIV 8

9 Patient Stigma Patient Motivation PrEP Barriers Lack of Access/Cost of Treatment Insured/Uninsured Copay/Deductible Cost PrEP Cost Manufacturer patient assistance program Uninsured patients High copay cost: Manufacturer copay card available Covers up to $300/month for Truvada High deductible Patient Access Network Will cover $4,000/year for eligible patients (500% federal poverty level) Important Points Reserved for high-risk individuals Serodiscordant couples, IDU, high-risk sexual behavior Adherence is crucial for prevention Significant barriers to treatment Need for increased education for providers and high-risk patients On Demand PrEP ANRS IperGay: 2 tablets 2-24 hours prior to sex 1 tablet 24 hours after sex 1 tablet 48 hours after initial dose 86% reduction in HIV Median of 16 tablets taken per month Pipeline Medications TAF Tenofovir alafenamide fumarate Prodrug of tenofovir Less serum drug exposure Can be dosed at 1/10 th dose of TDF Decreased renal/bone long term side effects Low levels in genital tissues Molina, et al. CROI Abstract 23LB. Horn, et al. HIV Preventative Technologies 2014;

10 Pipeline Medications Oral Maraviroc (monotherapy or combination) (phase II) Long-Acting Injectables Cabotegravir (phase II) Rilpivirine LA (phase II) Vaginal Rings Dapivirine vaginal ring (phase III) UNAIDS Getting to Zero Goals for HIV Prevention Sexual transmission of HIV reduced by half, including among young people, men who have sex with men and transmission in the context of sex work Vertical transmission of HIV eliminated and AIDS-related maternal mortality reduced by half All new HIV infections prevented among people who use drugs Horn, et al. HIV Preventative Technologies 2014; UNAIDS. Getting to Zero: Strategy. Question 1 Questions? Which of the following patients would be candidates for PrEP? 27 year old MSM with ongoing high risk sexual behavior of unprotected anal sex 30 year old nurse working in an HIV clinic who administers vaccines and other injections to HIV seropositive patients 35 year old HIV sero-negative man in a monogamous relationship with his sero-positive husband (husband has undetectable HIV viral load) A and C All of the above Question 2 Which of the following laboratory tests are recommended prior to initiating PrEP with TDF/FTC (Truvada)? Baseline third or fourth generation HIV test Serum Creatinine Serology for Hepatitis B and C STI screening All of the above Question 3 Which of the following are barriers to starting PrEP therapy? Treatment coverage/cost Stigma Patient motivation All of the above 10