Antiretroviral Therapy: Keys to Success

Details
Antiretroviral Therapy:Keys to Success Joanne Orrick Urban, PharmD, BCPS, AAHIVP Clinical Pharmacist North Florida AIDS Education and Training Center University of Florida Disclosure of Financial Relationships This speaker has the following financial relationship to disclose: Bristol-Myers Squibb (spouse's employer) This slide set has been peer-reviewed to ensure that there areno conflicts of interest represented in the presentation. 2 2 2 Objectives Discuss initial antiretroviral therapy (ART) options according to the most recent Department of Health and Human Services (DHHS) Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV List factors involved in selecting initial antiretroviral therapy (ART) Utilizing patient case scenarios, select initial regimens taking into account co-morbidities, drug-drug interactions, and patient preferences Identify resources to assist patients in maintaining access to ART Objectives Discuss initial antiretroviral therapy (ART) options according to the most recent Department of Health and Human Services (DHHS) Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV List the factors involved in selecting initial antiretroviral therapy (ART) Utilizing patient case scenarios, select initial regimens taking into account co-morbidities, drug-drug interactions, and patient preferences Identify resources to assist patients in maintaining access to ART HIV Treatment Guidelines Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV. Department of Health and Human Services. February 24, 2021. Available at https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-arv Unless otherwise noted, information in this presentation is adapted from these guidelines. 5 Recommended Initial Regimens for Most People with HIV INSTI + 2 NRTIs Bictegravir/tenofovir alafenamide/emtricitabine Dolutegravir/abacavir/lamivudine Only if HLA-B*5701 negative and no hepatitis B virus (HBV) coinfection Dolutegravir + tenofovir1 + (emtricitabine or lamivudine) Raltegravir + tenofovir1 + (emtricitabine or lamivudine) + OR + OR 1. Tenofovir alafenamide (TAF) or tenofovir disoproxil fumarate (TDF) OR 6 Recommended Initial Regimens for Most People with HIV (Continued) INSTI + 1 NRTI Dolutegravir/lamivudine Only if - HIV RNA < 500,000 copies/mL - no HBV coinfection - genotype results shows no reverse transcriptase resistance 7 INSTI + 2 NRTIs Elvitegravir/cobicistat/tenofovir1/emtricitabine Initial Regimens- Certain Clinical Situations Boosted PI + 2 NRTIs (In general, boosted darunavir preferred) /r or /c indicates ritonavir or cobicistat for boosting Darunavir/c or darunavir/r + tenofovir1 + (emtricitabine or lamivudine) Atazanavir/c or atazanavir/r + tenofovir1 + (emtricitabine or lamivudine) Darunavir/c or darunavir/r + abacavir/lamivudine Only if HLA-B*5701 negative and no HBV coinfection 1. Tenofovir alafenamide (TAF) or tenofovir disoproxil fumarate (TDF) NNRTI + 2 NRTIs Doravirine + tenofovir1 + (emtricitabine or lamivudine) Efavirenz + tenofovir1 + (emtricitabine or lamivudine) Rilpivirine/tenofovir1/emtricitabine If HIV RNA < 100,000 and CD4 > 200 Initial Regimens- Certain Clinical Situations 1. Tenofovir alafenamide (TAF) or tenofovir disoproxil fumarate (TDF) 9 TAF vs. TDF: What is the Difference? Antela, et al. HIV Medicine (2016), 17 (Suppl. 2), 4--16 Available at http://onlinelibrary.wiley.com/doi/10.1111/hiv.12401/pdf TAF vs TDF Drug Use for Hep B Use for PrEP Use in Pregnancy Increased lipids Renal Effects Weight Gain TAF Yes Yes1 Yes2 More3 Less More4 TDF Yes Yes Yes Less More Less TAF/FTC (Descovy) is approved for use in PrEP in men or transgender women who have sex with men Alternative NRTI in pregnant women or women trying to conceive(see https://clinicalinfo.hiv.gov/en/guidelines/perinatal/table-5-situation-s...) Higher LDL, HDL and triglycerides but no difference in total cholesterol/HDL ratio-clinical significance unknown More common in women and Black or Hispanic patients. 11 TAF vs. TDF-Use in Renal Dysfunction and Hemodialysis (HD) Drug CrCL (mL/min) Dose TAF < 15 and not on HD1 Not recommended < 15 and on HD2 One tablet once daily TDF 30-49 300 mg every 48 hours 10-29 300 mg twice weekly (every 72-96 hours) < 10 and not on HD No recommendation On HD2 300 mg every 7 days3 Recommendations vary depending on co-formulation used. See https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-arv/anti... Dose after HD if given on HD day(s) Assumes three HD sessions of 4 hours duration each 12 Patient Case Ricky Ricky is a 28 year old man who was recently discharged from the hospital where he was diagnosed with HIV/AIDS and disseminated Mycobacterium avium complex infection He comes to the clinic to initiate ART He states he has no preference with respect to food requirements or the need for a single tablet regimen but would prefer a once daily regimen Patient Case Ricky Labs: Genotype: pansensitive AST/ALT: WNL eGFR 103 mL/min VL 182,000 copies/mLCD4 43 cells/mm3 Allergies: NKDA Medications: rifabutin 300 mg po once daily, azithromycin 500 mg po once daily, ethambutol 1000 mg po once daily, trimethoprim/sulfamethoxazole 1 DS tab po once daily Why is a TAF-containing regimen not recommended for Ricky? TAF may not be as effective as TDF in patients with high viral loads Due to drug-drug interactions, TAF levels would be expected to be increased Due to drug-drug interactions, TAF levels would be expected to be decreased I'm not sure, I thought TAF could be used in all patients TAF Drug Interactions Strong P-glycoprotein (P-gp) inducers are expected to TAF concentrations Rifamycins (i.e., rifampin, rifabutin) St. John's Wort Carbamazepine Oxcarbazepine Phenytoin Phenobarbital Objectives Discuss initial antiretroviral therapy (ART) options according to the most recent Department of Health and Human Services (DHHS) Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV List the factors involved in selecting initial antiretroviral therapy (ART) Utilizing patient case scenarios, select initial regimens taking into account co-morbidities, drug-drug interactions, and patient preferences Identify resources to assist patients in maintaining access to ART Factors in Regimen Selection Viral load and CD4 cell count HIV resistance HLA-B*5701 status Co-morbid conditions Co-infections Pregnancy or pregnancy potential Potential adverse effects Potential drug-drug interactions Patient preferences Access/cost Specific Comorbid Conditions Comorbid Conditions E.g., Cardiovascular disease, hyperlipidemia, obesity, renal disease, osteoporosis or decreased bone density, psychiatric illness Coinfections: hepatitis C virus (HCV), hepatitis B virus (HBV), tuberculosis (TB) Regimen/Drug Factors Potential adverse effects Potential drug-drug interactions Convenience (e.g., pill burden, dosing frequency, food requirements) Regimen's genetic barrier to resistance (i.e., how easy is it for the virus to become resistant to the medicines in the event of missed doses) Cost Conversations About Patient Preferences and Barriers to Adherence Dosing frequency, pill burden, food requirements, size of pills, potential side effects What is the patient's typical day like? What time would be most convenient to take medications? It is best to tailor the regimen to predictable and routine daily events How will schedule differ on weekends? What will happen if they travel? Will the cost of medications impact access? Objectives Discuss initial antiretroviral therapy (ART) options according to the most recent Department of Health and Human Services (DHHS) Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV List the factors involved in selecting initial antiretroviral therapy (ART) Utilizing patient case scenarios, select initial regimens taking into account co-morbidities, drug-drug interactions, and patient preferences Identify resources to assist patients in maintaining access to ART Patient Case Cynthia Cynthia is a 28 year old woman recently diagnosed with HIV infection who presents to the clinic to start ART through a rapid start program Baseline labs: drawn at visit, not yet available. PMH: treated for chlamydia x 2 Social history: unmarried, never smoked, does not drink alcohol, has 1 child (3 years old) and is interested in having more. Her only birth control method is condoms. What regimen would you choose for Cynthia? BIC/TAF/FTC (Biktarvy) DRV/c + TAF/FTC (Prezcobix + Descovy) DTG + TAF/FTC (Tivicay + Descovy) DTG + TDF/FTC (Tivicay + Truvada) INSTI Risk of Neural Tube Defects Very small increased risk of neural tube defects seen with DTG Advantages of DTG include once daily dosing, well-tolerated, rapid viral suppression Perinatal guidelines now list DTG as a preferred agent throughout pregnancy and in women trying to conceive Guidelines stress importance of patient counseling and informed decision making See https://clinicalinfo.hiv.gov/en/guidelines/perinatal/whats-new-guidelines Patient Case James James is a 23 year old man recently diagnosed with HIV infection CD4 482 cells/mm3, VL 29,852 copies/mL (no resistance detected) eGFR 98 mL/min, CBC and CMP: WNL No hepatitis B coinfection He states he would prefer a one pill once a day regimen and does not want a regimen that has to be taken with food What regimen would you choose for James? DTG/3TC (Dovato) DTG/ABC/3TC (Triumeq) BIC/TAF/FTC (Biktarvy) RPV/TAF/FTC (Odefsey) DRV/c/TAF/FTC (Symtuza) ART with Food Requirements Should be Taken With Food Atazanavir (ATV, Reyataz)/r OR ATV/c (Evotaz) Darunavir/r (DRV, Prezista)/r OR DRV/c (Prezcobix) OR DRV/c/TAF/FTC (Symtuza) EVG/c/TDF/FTC (Stribild) OR EVG/c/TAF/FTC (Genvoya) ART with Food Requirements Should be Taken With a Full Meal Rilpivirine (Edurant) OR RPV/TDF/FTC (Complera) OR RPV/TAF/FTC (Odefsey) OR RPV/DTG (Juluca) Should be Taken on an Empty Stomach EFV/FTCTDF (Atripla) OR EFV (Sustiva) OR EFV/3TC/TDF (Symfi) Patient Case Alicia Alicia is a 58 year old woman recently diagnosed with HIV infection who is being seen to initiate ART Baseline resistance test: no mutations detected CD4 375 cells/mm3, VL 10,502 copies/mL eGFR 58 mL/min, AST 58, ALT 62 Hepatitis screening Hepatitis B infected, Hep B VL 1.2 million IU/mL Hepatitis C uninfected Hepatitis A nonimmune Which regimen below would NOT be appropriate for Alicia? DTG/3TC (Dovato) TDF/FTC (Truvada) + DTG (Tivicay) BIC/TAF/FTC (Biktarvy) DRVc/TAF/FTC (Symtuza) All of the above are appropriate options Regimens for HBV Coinfected Patients It is important to use two drugs that are active against hepatitis B in people with HIV infection and HBV coinfection Tenofovir (TAF or TDF) Emtricitabine (FTC) or lamivudine (3TC) Poor adherence or lapses in therapy in people with HBV can lead to severe liver disease including failure and death Patient Case Jessica Jessica is a 32 year old woman who was diagnosed with HIV infection in 2018. She is stable on a regimen of bictegravir/emtricitabine/tenofovir alfenamide (Biktarvy) VL < 20 and CD4 789 cells/mm3 on recent labs Concomitant medications: omeprazole 20 mg once daily, ethinyl estradiol/norgestimate (Sprintec) 1 tab daily, ferrous sulfate 325 mg twice daily (iron supplement) Which medication is expected to interact with BIC/TAF/FTC (Biktarvy)? Omeprazole Ethinyl estradiol/norgestimate Ferrous sulfate None of the above INSTI Interactions Objectives Discuss initial antiretroviral therapy (ART) options according to the most recent Department of Health and Human Services (DHHS) Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV List the factors involved in selecting initial antiretroviral therapy (ART) Utilizing patient case scenarios, select initial regimens taking into account co-morbidities, drug-drug interactions, and patient preferences Identify resources to assist patients in maintaining access to ART Patient Case Bill Bill is a 32 year old man with HIV infection who is seen at the clinic to restart ART He was previously well-controlled on bictegravir/tenofovir alafenamide/emtricitabine (Biktarvy) He has private insurance through his job and was using a local pharmacy that told him his copay was $1000. He got frustrated and fell out of care for 1 year. Patient Case Steven Patient came to your clinic to re-establish HIV care He stated that he has been well-controlled on efavirenz/emtricitabine/tenofovir disoproxil fumarate (Atripla) since 2009. HIV VL of < 20 and CD4 of 779 (25%) Copay used to be less than $10 but as of the 1st of the year, the copay increased to $900 per month. He paid the copay when he could but started taking the medication every other day to stretch it out. Client has Medicare but no longer has the low income subsidy 38 What resources could have been utilized to assist Bill and Steven in obtaining ART each month? Program Website Limitations Pharmaceutical company programs https://www.gileadadvancingaccess.com/ https://www.viivconnect.com/ https://www.merck.com/patients/patient-financial-assistance/ https://www.janssencarepath.com/ Cannot be used in patients with federally funded insurance (e.g. Medicare, Medicaid, Tricare) No income limitations Good Days www.mygooddays.org Can be used in patients with federally-funded insurance Income limitations Patient Advocate Foundation www.copays.org/funds/hiv-aids-and-prevention/ Can be used in patients with federally-funded insurance Income limitations Copay Assistance Programs Other Resources for Copays ADAP Premium Plus/copay assistance Ryan White medical case management Patient Case-Anna Anna is a 48 year old woman who is seen in the clinic for follow-up of HIV infection. She is well-controlled on a regimen of emtricitabine/tenofovir alafenamide/darunavir/cobicistat (Symtuza). HIV VL < 20, CD4 1032 (48%) She is suffering from migraines and her provider has prescribed a new medication since sumatriptan is no longer working for her. Patient Case-Anna Anna has no insurance and is currently on ADAP. She asks her Ryan White case manager for assistance in obtaining the medication since it is not on the ADAP formulary. You find out the medication is called galcanezumab-gnlm (Emgality) and costs over $800 per month. Medication Resources GoodRX-provides discount cards for medications https://www.goodrx.com/ Pharmaceutical assistance programs www.needymeds.org Ryan White medical case management Other area specific resources Adherence Interventions Prescription and/or co-pay assistance programs Community resources to promote adherence (e.g., family, peer advocates) Pillboxes, planners, alarms, cell phone apps Referral to specialty pharmacy Cabotegravir/rilpivirine (Cabenuva) Keys to Success Regimens are selected based on a variety of factors to optimize chances for treatment success Consider patient preferences in regimen selection Remember that patient circumstances change over time Let all patients know that there are resources to assist them in staying on ART and they should communicate any access issues to their provider or case manager immediately Keys to Success At every visit, assess any barriers to obtaining and taking medications Pharmacy not filling prescriptions on time Pharmacy providing partial antiretroviral regimen and/or filling medications on different dates throughout the month Lack of transportation to pick up medications Travel Inability to afford copays and/or insurance premiums Side effects Forgetting to take medication or not taking the same time each day http://www.seaetc.com/provider-resources/reference/ Antiretroviral Resources Update in progress http://aetc.medicine.ufl.edu/resources/drug-information-sheets / Antiretroviral Resources