WHAT'S NEW IN HIV? HIGHLIGHTS & NEW DATA ON HIV TREATMENT A PRESENTATION FOR HEALTHTRUST MEMBERS JUNE 18, 2021 SHIVANI PATEL, PHARMD PGY-1 PHARMACY RESIDENT ROBERT WOOD JOHNSON UNIVERSITY HOSPITAL NAVANEETH NARAYANAN, PHARMD, MPH, BCIDP CLINICAL ASSOCIATE PROFESSOR RUTGERS UNIVERSITY ERNEST MARIO SCHOOL OF PHARMACY CONFLICT OF INTEREST DISCLOSURE There are no relevant financial interest to disclose for myself or my spouse/partner within the last 12 months. The preceptor has a financial interest/arrangement, affiliation or relationship with Astellas and Merck that could be perceived as a real or apparent conflict of interest in the context of the subject of this activity. Note: This program may contain the mention of suppliers, brand products, services, or drugs presented in a case study or comparative format using evidence-based research. Such examples are intended for educational and informational purposes only and should not be perceived as an endorsement of any particular supplier, brand, product, service or drug. 1 2 3 LEARNING Identify new antiretroviral Describe a two-drug regimen Outline key counseling points agents and their role in the for treatment-naïve to a patient receiving new OBJECTIVES management of HIV/AIDS individuals and factors to antiretroviral agents related consider when selecting an to drug administration, initial regimen for an potential side effects, and individual. drug-drug interactions DRUG NAME ABBREVIATIONS Abbreviation Full Name Abbreviation Full Name Abbreviation Full Name 3TC Lamivudine DTG Dolutegravir NFV Nelfinavir ABC Abacavir EFV Efavirenz NVP Nevirapine ATV Atazanavir ETR Etravirine R5 CCR5-utilizing virus ATV/c Atazanavir/cobicistat EVG Elvitegravir RAL Raltegravir ATV/r Atazanavir/ritonavir FPV Fosamprenavir RPV Rilpivirine BIC Bictegravir FTC Emtricitabine RTV or r Ritonavir CAB Cabotegravir FTR Fostemsavir T-20 Enfuvirtide COBI or /c Cobicistat IBA Ibalizumab TAF Tenofovir alafenamide d4T Stavudine IDV Indinavir TDF Tenofovir disoproxil fumarate ddI Didanosine ISL Islatravir TMR Temasvir DLV Delavirdine LEN Lenacapavir TFV-DP Tenofovir-diphosphate DOR Doravirine LPV Lopinavir TPV Tipranavir DRV Darunavir MVC Maraviroc ZDV Zidovudine Source: DHHS: clinicalinfo.hiv.gov/en/guidelines. Prevalence-Based HIV Care Continuum EPIDEMIOLOGY US and 6 Dependent Areas, 2018 100 About 1.2 million people in 90 1 the U.S. are living with HIV 80 86 80 An estimated 36,400 new HIV 70 infections occurred in the 60 65 United States in 20181 50 56 HIV diagnoses overall declined 50 40 in 2009–18, however HIV diagnoses among individuals 30 aged 25–34 years increased 20 during the same period2 10 Percentage of people living withHIV of people living Percentage 0 Diagnosed Linked to Care Received Care Retained in Virally Care Suppressed Sources: 1. CDC. HIV Surveillance Report 2020; 31. 2. HIV.gov. Policies & Issues: HIV Care Continuum. May 2020. 3. Sullivan et,al. Lancet. 2021;397(10279):1095-1106. CCR5 Antagonist Post-attachment inhibitors Fusion Inhibitors NRTIs HIV VIRAL NNRTIs REPLICATION Protease CYCLE inhibitors (PIs) Integrase inhibitors (INSTIs) Source: The HIV Life Cycle. National Institutes of Health. https://hivinfo.nih.gov/understanding-hiv/fact-sheets/hiv-life-cycle. WHAT'S NEW IN THE GUIDELINES? Sources: DHHS: clinicalinfo.hiv.gov/en/guidelines. IAS-USA: Saag. JAMA. 2020;324(16):1651-1669 TREATMENT AS PREVENTION Using ART to consistently suppress HIV RNA < 200 copies/ml prevents transmission of HIV to sexual partners Patient should use another form of prevention for >6 months and until an HIV RNA <200 copies/mL High level of adherence is necessary Does not prevent transmission of STIs Source: HHS Adult and Adolescent Treatment Guidelines: https://clinicalinfo.hiv.gov/en/guidelines WHEN IS THE RIGHT TIME TO START ART? Start ART immediately or as soon as possible after diagnosis Panel supports same-day start “when possible” Exceptions to immediate starts: Tuberculous meningitis Cryptococcal meningitis Improve the rate Decrease the Reduce the risk Increase the of virological time to virologic of HIV uptake of ART suppression suppression transmission Sources: 1. HHS Adult and Adolescent Treatment Guidelines: https://clinicalinfo.hiv.gov/en/guidelines 2. Saag et al, JAMA. 2020;324(16):1651-1669. INITIAL ART FOR TREATMENT-NAÏVE INDIVIDUALS WHAT TO START? DHHS Recommendation (Dec 2019)1 IAS-USA Recommendation (Oct 2020)2 • 2 – drug regimen • 2 – drug regimen • Dolutegravir (DTG)/lamivudine (3TC) • Dolutegravir (DTG)/lamivudine (3TC) (if HIV RNA < 500,000 copies/ml, no HBV co-infection, or if results of (if HIV RNA < 500,000 copies/ml, no HBV co-infection, or if results HIV genotypic resistance testing not available) of HIV genotypic resistance testing not available) • 3 – drug regimens • 3 – drug regimens • Bictegravir (BIC)/tenofovir alafenamide • Bictegravir (BIC)/tenofovir (TAF)/emtricitabine (FTC) alafenamide (TAF)/emtricitabine (FTC) • Dolutagrevir/Abacavir (ABC)/ lamivudine (If HLA- • Dolutegravir plus B*5701 negative) • Tenofovir alafenamide/emtricitabine • Dolutegravir or raltegravir plus • Tenofovir disoproxil fumarate (TDF)/emtricitabine • Tenofovir alafenamide/emtricitabine • Tenofovir disoproxil fumarate/lamivudine • Tenofovir disoproxil fumarate (TDF)/emtricitabine • Tenofovir disoproxil fumarate/lamivudine Source: 1. DHHS: clinicalinfo.hiv.gov/en/guidelines Sources: 2. IAS-USA: https://jamanetwork.com/journals/jama/fullarticle/2771873 RECOMMENDED INITIAL REGIMENS FOR MOST PEOPLE WITH HIV DTG/ABC/3TC BIC/FTC/TAF (Triumeq) (Biktarvy) If HLA-B*5701(-) INSTI DTG/3TC INSTI + 2 NRTIs + NRTI (Dovato) DTG + FTC/TAF or TDF RAL/FTC/TAF or TDF (Tivicay with Descovy or (Isentress HD or Isentress with Truvada) Descovy or Truvada) SWITCH TO 2 DRUGVS. CONTINUE 3 DRUGS ART? TANGO TRIAL Source: Van, et al TANGO Study. Clin Infect Dis. 2020;71(8):1920-1929. TANGO: BACKGROUND Background: ongoing, open-label, multicenter, phase 3, non-inferiority trial comparing switching to DTG/3TC versus remaining on 3-4 TAF based regimen Maintain Regimen Switch Regimen TAF-Based Regimen DTG/3TC N = 372 N = 369 Primary endpoint: : Virologic response at 48 weeks Source: Van, et al TANGO Study. Clin Infect Dis. 2020;71(8):1920-1929. TANGO: VIROLOGIC OUTCOMES AT WEEK 48 & WEEK 96 48 weeks 93.2 93 DTG/3TC (N = 369) 86 TAF - based regimen (N = 372) 79 DTG/3TC TAF-based regimen Proportion of participants, % participants, of Proportion 20 48 weeks 96 weeks 48 weeks 48 weeks 48 weeks 14 0.3 0.5 0 1 6.5 6.5 4.6 0.8 6 2 3.5 0.5 4 1 HIV-1 RNA > 50 COPIES/ML HIV-1 RNA < 50 COPIES/ML NO VIROLOGIC DATA DRUG-RELTED AE WITHDRAWALS DUE TO AE Source: Van, et al TANGO Study. Clin Infect Dis. 2020;71(8):1920-1929. SWITCH TO DTG/3TC VS. CONTINUED TAF-BASED 3-DRUG ART TANGO: SUMMARY DTG/3TC was non-inferior in maintaining virologic suppression when compared to a TAF-based regimen at week 48 and even at week 96 No cases of treatment emergent resistance in virologically suppressed patients Weight change not significantly different: +0.81 kg with DTG/3TC vs +0.76 kg with continued TAF-based ART Lipid panel improved in the patient taking DTG/3TC, while it worsened in the TAF-based group Insulin resistance improved significantly after switching to DTG/3TC Take home point: GEMINI and TANGO trials have provided strong evidence that the two-drug regimen (DTG/3TC) is non-inferior to 3-4 drug regimen therefore the DTG/3TC has been recommended for initial treatment for most people with HIV Source: Van, et al TANGO Study. Clin Infect Dis. 2020;71(8):1920-1929. ASSESSMENT QUESTION # 1 Which of the following is a two-drug regimen approved for a treatment naïve individual living with HIV? A. Dolutegravir - rilpivirine B. Dolutegravir - lamivudine C. Emtricitabine - tenofovir alafenamide D. Abacavir - lamivudine ASSESSMENT QUESTION # 1 - RESPONSE Which one of the following is a two-drug regimen approved for a treatment naïve individual living with HIV? A. Dolutegravir - rilpivirine B. Dolutegravir - lamivudine C. Emtricitabine - tenofovir alafenamide D. Abacavir - lamivudine DOLUTEGRAVIR & NEURAL TUBE DEFECTS: UPDATE TSEPAMO & IMPAACT 2010 TSEPAMO STUDY – APRIL 2020 UPDATE NTD Prevalence 0.94 This is a surveillance study performed at 1 government maternity sites in Botswana since August 2014, with primary aim of evaluating 0.3 neuronal tube defects (NTDs) prevalence 0.19 0.12 0.11 associated with ARV exposure at conception 0.09 0.1 0.1 0.08 0.07 0.07 In May 2018, an unplanned analysis of TSEMPO 0.04 0.04 0.03 study reported increase in prevalence of IncidenceNTD NTDs after exposure to dolutegravir at conception 0.01 May-18 Apr-19 Apr-20 DTG Non-DTF EFV DTG - Pregnancy HIV negative Sources: 1. Zash et al, N Engl J Med. 2018;379(10):979-981. 2. Zash et al,. N Engl J Med. 2019;381(9):827-840. IMPAACT 2010 "VESTED STUDY" IMPAACT 2010 is a phase III, multicenter, ART-naïve, HIV three-arm, randomized, open-label, non- infected pregnant women at 14-28 inferiority study comparing the efficacy and weeks of gestation safety of a DTG based ART to an EFV- (N = 643) containing ART in HIV infected pregnant women Primary efficacy endpoint: maternal HIV-1 RNA < 200 copies/mL at delivery Arm 1: Arm 2: Arm 3: DTG + FTC/TAF DTG + FTC/TDF EFV/FTC/TDF Primary safety endpoints: adverse pregnancy composite outcome and mother and infant AEs Sources: Chinula L et al, Virtual CROI 2021, Abstract #177 IMPAACT 2010: VIROLOGIC SUPPRESSION AT DELIVERY Combined Women With HIV-1 RNA < 200 c/mL at Delivery, % EFV/FTC/TDF P Value DTG-Based ART ITT population 96.3