PrEP Guidelines for the Ob/Gyn. Outline. 1. How many patient have you discussed PrEP with this year?

Transcription

1 PrEP Guidelines for the Ob/Gyn Megan J. Huchko, MD, MPH Obstetrics and Gynecology Update October 14, 2015 I have no financial or other conflicts of interest to declare Outline The Need for PrEP: HIV Treatment and Prevention Gap What is the evidence? What is the role of the Ob/Gyn in PrEP? How do I provide PrEP? PrEP in Conception, Pregnancy and Breastfeeding 1. How many patient have you discussed PrEP with this year? A. Over 100 B. Between 50 and 100 C. Less than 50 D. Maybe a couple E. PrEP? I am ob/gyn, not an HIV specialist! O v e r % 1% B e t w e e n 5 0 a n d L e s s t h a n 5 0 8% M a y b e a c o u p l e 24% P r E P? I a m o b / g y n, n o t... 67% 1

2 Need for HIV prevention methods Prevention is the most effective and costeffective way to prevent morbidity and mortality related to HIV 50,000 new HIV-infections in US annually Women represent >75% of new cases due to heterosexual transmission African American women are at highest risk for heterosexual acquisition of HIV Antiretroviral Therapy as treatment and prevention Extends life expectancy Reduces complications related to HIV/AIDS Prevented maternal to child transmission (<1%) Treatment as Prevention: Effective ART can reduce HIV viral load and reduce the risk of HIV-transmission No documented transmissions between monogomous serodiscordant couples in which HIV+ partner is virally suppressed (HPTN052) 1 However. 1 Cohen MS, HPTN052, International AIDS Society, 2015 HIV in the US: Underdiagnosed and Undertreated New AIDS Cases and AIDS-Related Deaths in the United States 1,106,400-1,200,000 Number (in 000s) ~80% Diagnosed 874, ,000 ~40% Treated 437, ,600 ~20% of All HIV-Infected Are HIV RNA <50 copies/ml 209, ,992 Number of Cases New AIDS Cases AIDS-Related Deaths Prevalence Diagnosed Treated Smith MK, et al. PLoS One. 2012;9:e Gardner EM, et al. Clin Infect Dis. 2011;52: Burns DN, et al. Clin Infect Dis. 2010;51: Viral Suppression Year CDC. HIV Surveillance Report, 2010;vol 22. Published March

3 Potential Intervention Approaches to Prevent HIV Transmission What is PrEP? Decrease Source of HIV Infection Barrier protection STI treatment Blood screening ART Maternal-to-child transmission Decrease partner s viral load Treatment of acute HIV infection Alter Risk-Taking Behavior Condom promotion Individual intervention Couples intervention Community based intervention Structural intervention Decrease Host Susceptibility to HIV Infection Barrier protection STI treatment Oral PEP Oral PrEP Topical microbicides Vaccines Infection control Circumcision Pre-exposure prophylaxis with antiretroviral therapy to reduce the risk of HIV acquisition Daily, oral antiretroviral therapy given to adults at high-risk of HIV-acquisition Tenofovir 300mg and Emtricitabine 200mg (in fixeddose combination Truvada, or TDF/FTC) Once daily dosing Has been shown to reduce risk of HIV infection through sexual and IVDU exposures Approved in July 2012 by the FDA Mayer KH, et al. Am J Public Health. 2010;100: Biologic Plausibility Infants receiving pre and post-exposure prophylaxis has 68% reduction in perinatal acquisition Post-exposure prophylaxis within 72 of HIVexposure reduced HIV-risk by 81% Animal studies of vaginal and rectal PrEP suggested efficacy in preventing sexual transmission PrEP Trial Results Proof of efficacy study of topical tenofovir gel in women CAPRISA 004 First oral PrEP study of emtricitabine/tenofovir DF for MSM iprex Proof of efficacy studies in heterosexual adults in Africa Partners PrEP TDF2 (CDC4940) First trial of PrEP in people who inject drugs Bangkok Tenofovir Study 3

4 CAPRISA 004 Study: Heterosexual Women CAPRISA 004 Results: Cumulative Probability of HIV Infection Double-blind study South Africa sites (Kwa-Zulu, Natal) Sexually active HIVuninfected women not using barrier contraception Screened (n=2160) Randomization 1:1 Double-Blind Tenofovir Gel (n=445) Similar baseline demographic characteristics, sexual history/behavior, and contraception use Placebo (n=444) Administration of placebo/tenofovir DF gel Insert 1 dose within 12 hours before sex Insert 1 dose ASAP, within 12 hours after sex No more than 2 doses within 24 hours Probability of Infection Placebo Gel P=0.017 Tenofovir Gel Month Effectiveness (%): 47% 50% 47% 40% 39% (P=0.064) (P=0.007) (P=0.004) (P=0.013) (P=0.017) Abdool Karim Q, et al. Science. 2010;329: Abdool Karim Q, et al. Science. 2010;329: iprex Study: MSM and Transgender Women iprex Study Results: Cumulative Probability of HIV Infection Multinational study HIV-negative men or transgender women who have sex with men Screened (n=4905) Randomization 1:1 Study Outcomes HIV seroconversion Adverse events Metabolic effects HBV exacerbations Risk behavior and STIs (including HSV) Adherence Double-Blind TDF/FTC (n=1251) Similar baseline demographic characteristics (except mean age), sexual risk factors, STIs, and HBV status Placebo (n=1248) Drug resistance, HIV RNA level, immunologic response, and CD4 cell count assessed in people who become HIV positive during the study. Follow-Up 3324 person-years (median 1.2 years) Cumulative Probability of HIV Infection Placebo (n=1248) TDF/FTC (n=1251) P= Weeks Grant RM, et al. N Engl J Med. 2010;363: Grant RM, et al. N Engl J Med. 2010;363:

5 Partners PrEP Study: Serodiscordant Heterosexual Couples Partners PrEP Study: Cumulative Acquired HIV Infections Phase 3, Double-Blind Study Kenya, Uganda Serodiscordant, heterosexual couples (n=4758) (HIV-positive partner not yet eligible for ART) Normal liver, renal, hematologic values/function Randomization 1:1 All patients received comprehensive HIV prevention services. Double-Blind Tenofovir DF qd (n=1584) Primary Endpoints HIV infection in HIV-negative partner Safety Tenofovir/Emtricitabine qd (n=1579) Follow-Up Up to 36 months (median 23 months; 7830 person-years) Placebo (n=1584) Cumulative Acquired HIV Infection Placebo (n=1568) TDF/FTC (n=1568) Tenofovir DF (n=1572) Months Baeten J, et a. N Engl J Med. 2012;367: Baeten J, et a. N Engl J Med. 2012;367: TDF2 Study: PrEP in Heterosexually Active Young Adults in Botswana PrEP Effectiveness by Adherence Levels Phase 2 trial in heterosexual men and women (n=1219) Women: 45% Married: 94% Completed study: 67% Primary results HIV seroconversion (n=33) Daily oral TDF/FTC(n=9 [2 males/7 females]) Placebo (n=24 [10 males/14 females]) 62% reduction Results in women differed than that seen in the FEM-PrEP study, which showed no benefit Proportion HIV Seroconversion (ITT) Placebo (n=606) 62% Reduction (P=0.03) TDF/FTC (n=610) Years Thigpen MC, et al. N Engl J Med. 2012;367:

6 PrEP Guidelines Who can benefit from PrEP? CDC recommends PrEP for: Sexually active MSM (IA) Adult heterosexually active men and women at high risk of HIV acquisition (IA) Adult IDU (IA) Discussion for known HIV-discordant couples attempting conception Practice/Preexposure-Prophylaxis-for-the-Prevention-of-Human-Immunodeficiency-Virus ACOG Committee Opinion 1 : Who? Women in known sero-discordant relationships Sexually active women within a high HIV-prevalence area 2 or social network and one of the following: inconsistent or no condom use diagnosis of sexually transmitted infections exchange of sex for commodities (such as money, shelter, food, or drugs) use of intravenous drugs or alcohol dependence or both; incarceration partner(s) of unknown HIV status with any of the factors previously listed 1 Preexposure-Prophylaxis-for-the-Prevention-of-Human-Immunodeficiency-Virus 2 6

7 What is the role of the Ob/Gyn? Reproductive-aged women often see their ob/gyn as a primary care provider Many of our patients are at risk for HIV High-risk behavior with HIV-unknown partners Long-term relationships with HIV+ partners HIV providers do not routinely see partners to talk about PrEP HIV-risk and partner considerations around pregnancy and lactation are unique Acceptable risk may increase during conception, decrease during pregnancy and lactation Partners may be more engaged in care HIV prevention is a core family planning service CDC MMWR: Providing quality family planning services, Case: MM 2. Do you think MM is a good candidate for PrEP 31 yo HIV-negative woman sees you for routine gyn care No medical issues Had been on OCPs until recently Regular menses, no prior STDs, surgeries Partner recently tested positive for HIV, is in care and on ART Haven t been having intercourse since diagnosis Wants to know options for attempting pregnancy, breastfeeding and beyond to reduce her risk for HIV A. Yes, definitely B. Maybe C. No D. I would probably need to consult an HIV-specialist 88% 7% 0% 5% How do you counsel? Manage? Y e s, d e f i n i t e l y M a y b e N o I w o u l d p r o b a b l y n e e d t o... 7

8 CDC Guidelines for Healthcare Providers Before initiating PrEP Determine eligibility Counseling on importance of adherence for efficacy Beginning PrEP regimen Dosing and adherence support Follow-up while on a PrEP medication is being taken Monitor for HIV, STIs, risk behaviors and adherence, and safety Report any serious adverse events to the FDA s MedWatch Discontinuing PrEP Patient choice, safety concerns, or HIV infection CDC Guidelines for Healthcare Providers: Before Initiating PrEP Determine eligibility Take a sexual history! Document negative HIV antibody test immediately before starting PreP (within the week) Test for acute HIV infection if recent exposure and/or symptoms are present Determine pregnancy/breastfeeding status and pregnancy desires Provide contraception if indicated Confirm Long-term potential for ongoing, high risk for HIV acquisition Calculated creatinine clearance is >60 ml/min (C-G) Other recommended actions Screen for HBV (offer vaccine if susceptible; treat if present) Screen and treat as needed for STIs CDC Guidelines for Healthcare Providers: Beginning PrEP Medication Regimen Prescribe Tenofovir DF/Emtricitabine (300/200 mg) 1 tablet daily In general, prescribe no more than a 90-day supply Renew only after confirming patient remains HIV uninfected If HBV infected Consider TDF/FTC for HBV and HIV prevention Provide risk-reduction and PrEP medication adherence counseling and condoms CDC Guidelines for Healthcare Providers: Follow-Up While on PrEP Evaluate and support PrEP medication adherence at each follow-up visit (more often if needed) For women, assess pregnancy Every 2 to 3 months HIV antibody test (document negative result) Assess Risk behaviors and provide risk-reduction counseling and condoms STI symptoms (if present, test and treat as needed) Every 6 months Test for STI regardless of symptomatology (treat as needed) Every 3 months after initiation, then yearly while on PrEP Blood urea nitrogen Serum creatinine 8

9 CDC Guidelines for Healthcare Providers: Discontinuing PrEP Perform HIV test(s) to confirm HIV status If positive Discontinue PrEP Order and document CD4+ count, viral load and resistance testing Establish linkage to care Help with linkage to partner notification and testing For pregnant women, inform prenatal-care provider and coordinate care to maintain HIV prevention during pregnancy and breastfeeding If negative Continue PrEP at least 4 weeks after last exposure Establish linkage to risk-reduction support services as indicated If active HBV infection at initiation of PrEP Consider appropriate medication for continued treatment of HBV infection PrEP in Conception, Pregnancy and Breastfeeding Disco Survey: HIV- in a relationship with an HIV+ desire children 123 surveys started, 93 completed 90% want children with their HIV+ male partner 25% have tried to get pregnant with their HIV+ male partner 67% had vaginal sex without condom with HIV+ partner Condom use: 27% always, 42% half time, 31% never 42% have seen a provider to discuss ways to get pregnant 45% primary care, 80% HIV specialist, 35% OBGYN, 30% fertility specialist Most women are willing to use various methods to prevent transmission 53% are willing to use PrEP, 51% Timed unprotected sex, 84% ovulation prediction kit, 47% PEP, 62% sperm washing vaginal insemination, 22% IVF, 44% adoption, 9% insemination with donated sperm Still enrolling: PrEP in Conception, Pregnancy and Breastfeeding Peri-conception and pregnancy are times of increased HIV risk and susceptibility for women in HIV-discordant relationships PrEP can be used to reduce the risk of transmission to both mother and baby Long-term effects of TDF/FTC on neonate are limited Most trials excluded or discontinued pregnant women PrEP trial showed no difference in pregnancy rates, birth outcomes or infant growth between placebo, TDF and TDF/FTC arms among women with incident pregnancies WHO recommends TDF/FTC for all pregnant and breastfeeding women for PMTCT TDF or TDF/FTC are widely used in reproductive aged women for HIV care and continued in pregnancy No trial or registry data show signals of adverse events ACOG Committee Opinion: Pregnancy and PrEP The drug combination of TDV and FTC is commonly used during pregnancy and has a reassuring safety profile. Practice vigilance for new HIV infections in lactating women Mugo, et al. JAMA, Jul Practice/Preexposure-Prophylaxis-for-the-Prevention-of-Human-Immunodeficiency-Virus 9

10 Providing PrEP in Conception & Pregnancy Partner should be on effective ART to reduce viral load Provider should review all options for safe conception, including assisted reproductive technology Semen analysis and, if indicated by history, HSG to prevent unnecessary exposure if likelihood of pregnancy is low STI screening in both partners Adherence counseling Start PrEP 1 month prior and continue 1 month post-exposure Recommend limiting sex without a condom to peak fertility times Cervical mucus checks Ovulation prediction kits If pregnant: HIV testing monthly, with viral load if signs of acute infection and at 36 wks Financial Considerations Private and public insurance plans vary in coverage for PrEP Gilead Sciences has a PrEP medication assistance program that provides: Truvada (TDF/FTC) to providers for eligible patients Access to free HIV testing Co-pay assistance for medical visits Free condoms Billing/ICD-10 Codes: Z20.6 Contact with and suspected exposure to viral HIV/AIDS virus Z71.7 Human Immunodeficiency Virus Counseling accessed October 1, 2015 Our Case: MM Resources for Providers Does she seem like a good candidate for PrEP? Screen for HIV, HepB and other STIs; check CrCl Discuss reproductive desires Provide LARC if desired Start Truvada Adherence counseling, continued indication for PrEP at each visit Check HIV, BUN/Cr q3 months; STI testing q6 mos Questions? NCCC Warmline: Decision-support tools, flowsheets and checklists: ACOG Committee Opinion Preexposure Prophylaxis for Prevention of HIV, May AIDS Info ( The National Network of STD/HIV Prevention Training Centers ( The AIDS Education Training Centers National Resource Center ( The National HIV/AIDS Clinicians Consultation Service ( NCCC Warmline: HIVE: 10

11 Resources for Patients Project Prepare Website: Centers for Disease Control and Prevention: Project inform: A new option for safer loving for women in Spanish and English San Francisco Department of Public Health: PrEP watch: Bay Area Perinatal AIDS Center: Positive Reproductive Outcomes for Men: Positively Negative: Acknowledgements Ian McNicholl, PharmD (slides) Shannon Weber at HIVE Nika Seidman Deb Cohan Jennifer Cocohoba, PharmD iprex Study: Comprehensive Package of Prevention Services All subjects received HIV testing, risk-reduction counseling, condoms, and diagnosis and treatment of symptomatic STIs At 24-week intervals, subjects screened for Asymptomatic urethritis, syphilis, antibodies to HSV-2, genital warts/ulcers Treatment was provided when indicated Sexual partners Offered treatment of STIs As needed, linkage to local prevention and treatment services Counseled on the use of conventional methods to protect from HIV HBV vaccination offered to susceptible subjects Grant RM, et al. N Engl J Med. 2010;363:

12 Partners PrEP Study: Comprehensive Prevention Services Risk reduction counseling (individuals and partners) Free condoms and condom counseling Contraception counseling and provision Screening and treatment for STIs Counseling and referral for other HIV-prevention interventions (eg, male circumcision), per national policies Worldwide Treatment and Prevention Gaps (2011) On ART: 8 million Number needing ART: 15 million New infections: 2 million annually People were waiting to become treatmenteligible, sicken, or die: ~24 million Estimated coverage of ART in low- and middle-income countries: 36% Baeten J, et a. N Engl J Med. 2012;367: Granich R, et al. Curr Opin HIV AIDS. 2013;8: