Simplifying HIV Treatment Now and in the Future

Transcription

1 Simplifying HIV Treatment Now and in the Future David M. Hachey, Pharm.D., AAHIVP Professor Idaho State University Department of Family Medicine Nothing Disclosure 1

2 Objectives List current first line agents for the treatment of HIV Describe two ways HIV regimens may be simplified Identify the role of newly approved agents Educate patients about future approaches to the treatment of HIV Discuss primary care prevention strategies to reduce morbidity and mortality GETTING TO 2019 WHAT DO WE KNOW 2

3 CASE Jane is 32 year old African American female living with HIV for 10 years. Her CD4 count is 550 cells/mm and her viral load is undetectable. She currently takes the following Kaletra (lopinavir/ritonavir) 2 tablets BID Combivir (zidovudine/lamivudine) 1 tablet BID Is Jane : Meeting goals of therapy? Receiving the standard of care? Transmission Risk Factors 3

4 Ethnicity Distribution Why 4

5 HIV Care Cascade 5

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9 Goals of Therapy Goals of therapy Reduce HIV-associated morbidity and prolong the duration and quality of survival Restore and preserve immunologic function Maximally and durably suppress plasma HIV viral load Prevent HIV transmission Evidence and support Reduces HIV-related morbidity and mortality Decreased perinatal transmission Reduced CVD and other EOD Delays drug-resistance mutations 9

10 Zidovudine Drug Approval Timeline Lamivudine Saquinavir Zacitabine Kaletra Trizivir Combivir Delaviridine Nelfinavir Biktarvy Triumeq Cimduo Delstrigo Stribild Doravirine Etravirine Ibalizumab Symtuza Epzicom Atripla Truvada Darunavir Odefsey Descovy Didanosine Stavudine Indinavir Nevirapine Ritonavir Efavirenz Abacavir Tenofovir DF Atazanavir Emtricitabine Enfurvitide Fosamprenavir Tipranavir Raltegravir Maraviroc Rilpivirine Complera Dolutegravir Genvoya Prezcobix Juluca 10

11 Standard Approach to Therapy Choose one Anchor Drug from one of the following classes Integrase inhibitors Protease inhibitors Non-nucleoside reverse transcriptase inhibitors Choose a Backbone consisting of Two nucleoside reverse transcriptase inhibitors Recommended Initial Regimens for Most PLWH Class Therapy Pill Burden Raltegravir + Tenofovir-Emtricitabine AM PM INSTI-Based Dolutegravir-Abacavir-Lamivudine Dolutegravir + Tenofovir-Emtricitabine Bictegravir-Tenofovir AF-Emtricitabine 11

12 SIMPLIFICATION WHY AND HOW CASE Jane inquires when picking up her medications that she has heard there are newer agents for treatment of HIV. She states this is her only regimen she has taken, has always been adherent, and has no resistance. Her copay is $25 per medication and she states that is a barrier for her. Describe to Jane two benefits of simplifying her regimen Recommend one single-tablet regimen Jane could use to simplify 12

13 Barrier to Resistance Rationale for Simplifying Managing or preventing side effects Limit exposure Reducing pill burden Avoiding food restrictions Reducing/eliminating drug interactions Eliminating drugdisease risks Lower costs / insurance requirements Updating to a preferred regimen Higher barrier to resistance Potency and Genetic Barrier to Resistance Backbone Anchor c-r/drv DTG BIC r/lpv MVC c-r/atv ZDV D4T TDF TAF ddi 3TC FTC ABC NVP ETR RPV EVG ENF RAL EFV Potency Modified from: Tang MW, Shafer RW. Drugs. 2012:72:e1-e25. 13

14 Single Tablet Regimens There are currently nine single tablet regimens that contain an anchor drug and two backbone agents 4 contain an anchor drug with high barrier to resistance and high potency Reduces copay and allows for complete regimen administration Two-Drug Regimens There have been 8 clinical trials examining two-drug simplification Candidates for these studies generally have high adherence rates and no drug resistance 14

15 Two-Drug Simplification Dolutegravir-Rilpivirine Juluca (FDA approved) Patients need to be suppressed for 6 months on 3-drug regimen before switch No resistance Adhere to food requirements Dolutegravir-Lamivudine HIV-1 RNA <50 c/ml, % b [CELLREF] Virologic outcome Study visit 90 DTG + 3TC (N=716) DTG + TDF/FTC (N=717) Not FDA Approved 91 CASE Benefits for Jane Reduce side effects Reduce pill burden Single copay Higher barrier to resistance and more potent agents Avoiding food restrictions Options for Jane 3-drug regimens Biktarvy (STR) Bictegravir/TAF/FTC Triumeq (STR) Dolutegravir/3TC/ABC 2-drug regimens Juluca (STR) 15

16 IS NEWER BETTER? New Agents Since 2015 Tenofovir Alafenamide (NRTI) Bictegravir (Integrase Inhibitor) Doravirine (NNRTI) Ibalizumab (Entry Inhibitor) 16

17 Tenofovir Tenofovir Diproxil Fumarate (TDF) Approved early 2000 s Component of several fixed dosed tablets 300 mg Long-term toxicities Osteoporosis Renal problems Larger tablets Tenofovir Alafenamide (TAF) Made available 2015 Component of several fixed dose tablets 25 mg and 10 mg Long-term toxicities No bone/renal Less favorable lipid profile Tenofovir 17

18 Bictegravir Integrase inhibitor available as a fixed dose tablet with NRTI backbone Biktarvy Potent and high barrier to resistance Favorable drug interaction and side effect profile Headache and insomnia most common, but rare Doravirine Non-nucleoside reverse transcriptase inhibitor available alone or in combination with NRTI backbone Pifeltro - single agent Delstrigo combination product When compared with other drugs in it s class: No interactions with proton pump inhibitors No food restrictions Well tolerated 18

19 Ibalizumab Unique monoclonal antibody that prevents entry into the CD4 cells Given via IV infusion every two weeks Needs to be combined with other agents High cost Reserved for rare circumstances Is Newer Better Tenofovir Alafenamide Maybe Conflicting data, but many providers favor TAF over TDF Bictegravir YES Risen to the top for most providers as the go to drug Doravirine No May be used in certain circumstances, but not necessarily better than other NNRTIs Ibalizumab Maybe Novel drug, but specific uses 19

20 HIV-1 RNA <50 c/ml, % WHAT S NEXT Long-Acting Injectable Cabotegravir (INSTI) + Rilpivirine (NNRTI) Integrase inhibitor with a high barrier to resistance and extremely long half life Both agents are able to be formulated into a long acting injectable suspension Week Virologic Outcomes Virologic success 84 CAB + RPV LA Q8W (n=115) CAB + RPV LA Q4W (n=115) CAB + NRTIs PO (n=56) Virologic nonresponse 13 No virologic data 14 20

21 Long-Acting Injectable What We Know Oral lead in Injections are high volume given in the gluteal muscle Need a provider (or pharmacist?) trained to administer agent What We Don t Know Who are going to be the best candidates How will this work in rural settings What happens when someone becomes nonadherent Resistance risk Cost Future of Antiretroviral Therapy HIV-1 discovered ZDV/3TC ZDV monotherapy Triple Drug Therapy Single Tablet Regimens The Integrase Era Long Acting Injectable? 2-drug regimens Implantable ART bnabs for therapy

22 Improving Quality and Duration of Life PRIMARY CARE STRATEGIES Primary Care Management Cardiovascular Risk Hypertension Myocardial infarction Hyperlipidemia Diabetes Chronic kidney disease Osteoporosis Smoking Lung disease Cancer screening Colon Prostate Breast Lung Cervical Anal 22

23 HIV Prevention (PrEP) HIV Care Cascade Rapid testing for HIV at the pharmacy Connecting new patients to a provider Late to therapy calls and 90 day fills Pre-Exposure Prophylaxis (PrEP) 23

24 Summary List current first line agents for the treatment of HIV Describe two ways HIV regimens may be simplified Identify the role of newly approved agents Examine patients about future approaches to the treatment of HIV Discuss primary care prevention strategies to reduce morbidity and mortality 24