HIV Rapid Start / PrEP

HIV Rapid Antiretroviral Therapy (ART)/ Preexposure Prophylaxis (PrEP) Lori Fantry, MD, MPH Professor of Clinical Medicine University of Arizona 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). 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Apr-21 2 Learning Objectives By the end of this presentation, you will be able to: Discuss how rapid initiation of HIV treatment results in improved patient outcomes and reduced HIV transmission Discuss current recommendations for monitoring patients on PrEP to ensure efficacy, safety, and prevention of HIV and other sexually transmitted infections (STIs) Compare and contrast FDA approved regimens for PrEP to improve clinical outcomes Apr-21 3 Ending the HIV Epidemic Starts with Testing Link to the CDC's HIV testing information Apr-21 4 Plan A: Treat All Treat Fast Reduce the time in which a person with HIV can get an HIV associated condition Reduce the time of infectivity Apr-21 5 Apr-21 Proportion of Viral Load <200 copies/mL over time from clinical referral in Months Christopher D. Pilcher et al. The Effect of Same-Day Observed Initiation of Antiretroviral Therapy on HIV Viral Load and Treatment Outcomes in a U.S. Public Health Setting. J Acquir Immune Defic Syndr. 2017 Jan 1; 74(1): 4451. 6 Apr-21 Relative Risk (95% CI) for Standard Care versus Same Day ART 7 Remaining in Care No evidence that Rapid ART start resulted in > likelihood of remaining in care (two cohorts: RR 0.97, 95% CI 0.791.18; low-quality evidence). Study reported risk of lost to follow-up at 3 months (RR 1.97, 95% CI 1.213.20) Apr-21 Ford N, Migone C, Calmy A, et al. Benefits and risks of rapid initiation of antiretroviral therapy.AIDS. 2018;32(1):17-23. doi:10.1097/QAD.0000000000001671 8 What would make you delay ART? Cryptococcal meningitis Kaposi's sarcoma Undetectable viral load CD4 cell count 700 Pneumocystis jiroveci pneumonia Apr-21 9 ONLY 51% OF PERSONS LIVING WITH HIV ARE VIRALLY SUPPRESSED Apr-21 PLAN B: PREP 10 What is PrEP? PrEP = preexposure prophylaxis Antiretroviral therapy (ART) given to an individual without HIV 99% efficacy when taken as prescribed Apr-21 11 Tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) (Truvada) FDA approved 7/16/12 Indicated for all with high risk of HIV infection Apr-21 12 Tenofovir alafenamide (TAF)/FTC (Descovy) FDA approved 10/3/19 Indicated for Men Transgender women Not for cisgender women Apr-21 13 Possible PrEP CandidatesPeople at ongoing, substantial risk of acquiring HIV infection Adult or adolescents 35 kg (77 pounds) Partner's HIV status unknown Men who have sex with men (MSM) Persons who inject drugs (PWID) who share equipment Persons with STIs Person's partner has HIV risk factors Female partners of MSM Partners of PWID Candidates for PrEP are people at ongoing, substantial risk of acquiring HIV infection. Link to CDC's HIV PrEP Guidelines for 2017 Apr-21 14 Candidates for PrEP are people at ongoing, substantial risk of acquiring HIV infection. The next few slides will show several groups to consider as candidates for PrEP. 14 People with STIs within 6 months MSM Gonorrhea Chlamydia Syphilis Heterosexuals Gonorrhea Syphilis Apr-21 15 Partner living with HIV Partner not taking ART OR HIV-infected partner VL >200 copies/ml If not recommending PrEP, must have recent viral load documenting VL <200 copies/ml Apr-21 16 Pregnancy PrEP not contraindicated Risk benefit changes Risk to fetus if woman taking PrEP Apr-21 17 Case Study: Michele Michele is a 23-year-old women who presents to Planned Parenthood for an HIV test. She has no complaints. She had chlamydia 4 months prior to the visit. PMH: 2014 Gonorrhea SH: Sexually active with 6 men in the past year. HIV, IDU, and sex with men status unknown Uses condoms 40% of the time Smokes ppd Drinks alcohol occasionally No illicit drugs. Apr-21 18 What would you recommend for Michele? HIV screening STI screening Birth control Daily TDF/FTC All of the above Apr-21 19 You decided to start Michele on PrEP. What tests will you order next? HIV test Liver Function tests Creatine clearance All the above A and C Apr-21 20 Testing prior to PrEP: HIV testing Hepatitis B antigen Hepatitis B surface antibody Hepatitis B core antibody Hepatitis C serology Estimated creatinine (eCrCl) Syphilis (RPR) Gonorrhea/chlamydia MSM any site of contact (urine, oral, rectal) Gonorrhea Heterosexual men urine Women vaginal preferred over urine Pregnancy Testing Apr-21 21 HIV Testing Within 7 days of starting Repeat if longer Repeat if suspect acute HIV May do viral load but false + with viral loads < 3000 copies/mL Apr-21 22 Acute HIV definition of acute Fever (75%) Fatigue Myalgia Skin rash Headache Pharyngitis Cervical adenopathy Arthralgia Night sweats Diarrhea (27%) Clinical presentation and diagnosis of primary HIV-1 infection by Daar ES, Pilcher, CD and Hecht FM (2008) Apr-21 23 These are the most common symptoms of acute HIV, with fever being the most common (75%), and diarrhea the least common on the list (27%). Hepatitis B Testing TDF/FTC and TAF/FTC also used to treat hepatitis B virus (HBV) Follow up with hepatitis B experienced provider If HBV patient started on TDF/FTC or TDF/FTC and discontinues May "flare" of hepatitis Apr-21 24 When an uninfected person takes Truvada before an exposure, the drugs accumulate in cells that are susceptible to infection so any virus that does enter the body never has a chance to make any copies; replication is blocked from the very start. PrEP Initiation Visit - Labs Evaluate for recent exposure to HIV or acute HIV Review labs Counsel Risk behavior reduction Adherence Prescribe eCrCl 60 ml/min TDF/FTC (Truvada) eCrCl 30 ml/min TAF/FTC (Descovy) Apr-21 25 TAF/FTC and TDF/FTC and Short-Term Side Effects (lasts 1 month) TAF Headache Nausea(with or without vomiting) Fatigue Unintentional weight gain TDF Headache Nausea(with or without vomiting) Flatulence Unintentional weight loss Apr-21 26 TDF/FTC Long Term Side Effects Nephrotoxicity Small decreased eCrCl may occur Clinically insignificant Rarely progressive Usually reversible Loss of bone mineral density Small decrease in bone mass within the first 6 months 25% of patients on long-term TDF Rarely progressive Usually reversible Incidence of fractures no different than placebo Apr-21 27 Long Term Side Effects of PrEP on Renal Function by Age Group Apr-21 28 How often should individuals on PrEP be tested for HIV? Every 30 days Every 3 months Every 6 months Once a year Apr-21 29 Follow up at least every 3 months HIV (antibody and antigen) Gonorrhea/chlamydia MSM any site of contact (urine, oral, rectal) Gonorrhea Heterosexual men urine Women vaginal preferred over urine RPR Pregnancy testing Counseling Apr-21 30 At least every 6 months Monitor Creatinine Clearance More frequent if HTN, diabetes, and other risk factors Continue PrEP even if Decrease eCrCl if remains 60 ml/min and not steadily declining If eCrCl < 60 ml/min, change to TAF/FTC If steady decline, change to TAF/FTC Apr-21 31 At least annually Hepatitis C testing Apr-21 32 On-Demand = Intermittent = Non-daily = Event Driven PrEP Apr-21 33 On-Demand PrEP Effective prevention for gay and bisexual men No data on heterosexual men or women Some health departments in Canada and US offer guidance NOT part of CDC's guidelines. CDC still recommends daily dosing Apr-21 34 Future directions of PrEP Cabotegravir LA (injectable) every 2 months Islatravir po every 28 days Islatravir implant yearly Combine with hormonal contraceptive Vaginal insert with TAF and elvitegravir Macaques (Dobard CROI 2020) Broadly neutralizing antibodies Dapivirine Vaginal Ring Apr-21 35 Case Study: Paul Paul is a 30-year-old man with no medical problems presents to the Maricopa County Health Department for an HIV test. He complains of some burning with urination. He had chlamydia 4 months prior to the visit. SH: Sexually active with men and women 4 partners in the past year. Unknown HIV status Uses condoms 60% of the time Does not smoke Drinks alcohol occasionally No illicit drugs. Apr-21 36 What would you recommend for Paul? Monthly islatravir Daily TDF/FTC On-Demand TDF/FTC Daily TAF/FTC Apr-21 37 Challenges 18.1% of US population at risk for HIV on PrEP Knowledge of PrEP among patients is lowest in African Americans Women Hispanics Uptake lowest in African Americans Hispanics Women (4% of women at risk on PrEP) Retention low in all groups Apr-21 38 Solutions Increase knowledge among African Americans, Hispanics, and women Increase patient access with more health care sites providing PrEP Availability at health care sites including those that provide care to groups at risk with low uptake Increase provider PrEP awareness 76% of primary care providers aware of PrEP 28% of primary care providers familiar with PrEP prescribing Link to PubMed article: PrEP Awareness, Familiarity, Comfort, and Prescribing Experience among US Primary Care Providers and HIV Specialists by Petroll et. al. (2018) Apr-21 39 When in Doubt, Get Help! Contact UA ID 520-626-6887 National Clinician Consultation Center, University of California San Francisco Apr-21 40 References Link to CDC site: PrEP (Updated 11/3/20) Link to Low Risk of Proximal Tubular Dysfunction Associated With Emtricitabine-Tenofovir Disoproxil Fumarate Preexposure Prophylaxis in Men and Women by Mugwanya et. al. (2016) Link to Effects of Emtricitabine/Tenofovir on Bone Mineral Density in HIV-Negative Persons in a Randomized, Double-Blind, Placebo-Controlled Trial by Mulligan et. al. (2015) Link to Panel on Antiretroviral Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Antiretroviral Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Accessed 12/28/19 Apr-21 41 Additional References Link to: How safe is TDF/FTC as PrEP? A systematic review and meta-analysis of the risk of adverse events in 13 randomised trials of PrEP by Pilkington et. al. (2018) Link to: Changes in Kidney Function Associated With Daily Tenofovir Disoproxil Fumarate/Emtricitabine for HIV Preexposure Prophylaxis Use in the United States Demonstration Project by Tang et. al. (2018) Link to CDC site: Preexposure prophylaxis for the prevention of HIV infection in the United States - 2017 update, a clinical practice guideline Apr-21 42