HIV Management Describe the HIV life cycle and recognize Update - PDF document

9/30/15 ¡ Pharmacist Learning Objectives HIV Management • Describe the HIV life cycle and recognize Update 2015 antiretroviral drug targets • Classify an antiretroviral agent by its mechanism of action • Summarize pertinent changes to the 2015 DHHS HIV guidelines Larry Pineda, PharmD, PhC, BCPS Visiting Assistant Professor • List the antiretroviral agents which are recommended for the treatment of HIV+ patients Pharmacy Practice and Administrative Science ljpineda@salud.unm.edu • List the antiretroviral agents which are recommended for post exposure prophylaxis (PEP) Technician Learning Objectives Human Immunodeficiency Virus (HIV) • Define HAART • Retrovirus (RNA) • Two distinct groups: HIV-1, HIV-2 • Identify the minimum number of antiretroviral drugs in an appropriate HAART regimen • Acquired Immune Deficiency Syndrome (AIDS) • Understand the importance of HAART • Transmission adherence • Sex • Injection drug use • List the antiretroviral agents which are • Perinatal recommended for post exposure prophylaxis • Breast milk (PEP) • HIV/AIDS among leading causes of morbidity/ mortality in U.S. Mature HIV Virion Natural Progression of HIV Stage ¡3 ¡ Stage ¡1 ¡ Stage ¡2 ¡ http://tuningpp.com/hiv-to-aids-progression/ 1 ¡

9/30/15 ¡ Epidemiology “Late Testers” in New Mexico • 1.2 million persons 13 years and older living • Diagnosed in stage 3 with HIV in U.S. 1 • 43.2% diagnosed with HIV received concurrent • 168,300 (14%) are unaware of their infection 1 AIDS diagnosis • Undiagnosed responsible for over half of new HIV • Relatively higher than U.S. average 38% cases 2 • Only ~50% of U.S. adults ever tested 3 • CDC expanded screening 2006 • Annual incidence approximately 50,000 cases 1 1. http://www.cdc.gov/hiv/library/reports/surveillance/index.html 2. Marks G et al. AIDS . 2006;20:1447-50 New Mexico DOH Summer Quarterly Report: July 2010 3. Kaiser Family Foundation, 2011 Survey of Americans on HIV/AIDS Living With HIV Early Initiation of Therapy • Improves outcomes 1 • Prevents progression to AIDS • Reduce hospitalizations • Decrease risk of opportunistic infections • Long healthy life • Reduces chance of transmitting to others 2 • Undetectable viral load <4% risk • Condom use + undetectable viral load <1% risk 1. Kitahata MM et al. N Engl J Med. 2009;360(18):1815-26 Campsmith M et al. JAMA 2008;300(5):520-29 2. Das M et al. PLoS One. 2010;5(6):e11068 Question HAART What is the minimum number of antiretroviral • Highly Active Anti-Retroviral Therapy drugs that should be included in an ideal HIV • 3 active antiretroviral drugs treatment regimen? • 2 nucleoside reverse transcriptase inhibitors • Plus 3 rd active agent: A. One • Integrase strand transfer inhibitor B. Two • Non-nucleoside reverse transcriptase inhibitor C. Three • Protease inhibitor with pharmacokinetic enhancer D. Four (cobicistat, ritonavir) E. Five • Adherence critical for success 2 ¡

9/30/15 ¡ Question Adherence Goal > 95% What is the percentage of adherence to HAART needed for optimal virologic supression? A. < 70% B. 70 – 79.9% C. 80 – 89.9% D. 90 – 94.9% E. > 95% Patterson DL et al. Ann Intern Med. 2000;133:21-30 The Drugs Antiretroviral Drug Classes • Entry inhibitor • Fusion inhibitor • Reverse transcriptase (RT) inhibitors • Nucleoside RT inhibitors (NRTI) • Non-nucleoside RT inhibitors (NNRTI) • Integrase strand transfer inhibitors (INSTI) • Protease inhibitors (PI) HIV Life Cycle Entry/Fusion Inhibitors • Selzentry (maraviroc) • CCR5-inhibitor • Requires tropism assay • Twice a day • Fuzeon (enfuvirtide) • Subcutaneous injection • Twice a day www.aidsinfonet.org 3 ¡

9/30/15 ¡ NRTIs NNRTIs • Truvada (tenofovir/emtricitabine) • Sustiva (efavirenz) • Viread (tenofovir) • Atripla (efavirenz/tenofovir/emtricitabine) • Emtriva (emtricitabine) • Once a day • Edurant (rilpivirine) • Epzicom (abacavir/lamivudine) • Complera (rilpivirine/tenofovir/emtricitabine) • Ziagen (abacavir) • Epivir (lamivudine) • Once a day • Viramune (nevirapine) • Combivir (zidovudine/lamivudine) • Intelence (etravirine) • Retrovir (zidovudine) • Twice a day PIs INSTIs • Prezista (darunavir) • Isentress (raltegravir) • Twice a day • Reyataz (atazanavir) Stribild ¡ • Vitekta (elvitegravir) • Norvir (ritonavir) • Needs to be boosted • Tivicay (dolutegravir) • Prezcobix (darunavir/cobicistat) Tivicay ¡ Triumeq ¡ • Evotaz (atazanavir/cobicistat) • Stribild (elvitegravir/cobicistat/tenofovir/ emtricitabine) • Triumeq (dolutegravir/abacavir/lamivudine) DHHS HIV Guidelines 2015 INSTI-Based Regimens • Updated April 2015 • Dolutegravir/abacavir/lamivudine (AI) • Only if HLA-B*5701 negative • 5 recommended HAART regimens: • Dolutegravir plus tenofovir/emtricitabine (AI) • 4 integrase strand transfer inhibitor (INSTI)-based regimens • Elvitegravir/cobicistat/tenofovir/emtricitabine • 1 ritonavir-boosted protease inhibitor (PI/r)-based (AI) regimen • Raltegravir plus tenofovir/emtricitabine (AI) • 2 regimens previously categorized as recommended moved to alternative 4 ¡

9/30/15 ¡ PI-Based Regimen Alternative List • Darunavir/ritonavir + tenofovir/emtricitabine (AI) • Limitations for use in certain patient populations • Atazanavir/ritonavir has been moved to • May be the preferred regimen for some patients alternative list • NNRTI-based regimens • Efavirenz/tenofovir/emtricitabine (BI) • Rilpivirine/tenofovir/emtricitabine (BI) • PI-based regimens • Atazanavir/ritonavir + tenofovir/emtricitabine (BI) • Atazanavir/cobicistat* + tenofovir/emtricitabine (BI) • Darunavir/ritonavir + abacavir/lamivudine (BII) * Creatinine clearance 70 ml/min Triumeq Prezcobix • Dolutegravir/abacavir/lamivudine • Darunavir/cobicistat • One pill once a day, with/without food • One pill once a day, with food • Adverse effects • Adverse effects • Headache • Diarrhea, nausea, vomiting • Insomnia • Rash • Rash, hypersensitivity reaction • Increased serum creatinine • HLA-B*5701 negative only • Treatment-naïve only • Drug interactions • Drug interactions • Polyvalent cations, separate • CYP-3A4 substrates • http://www.hiv-druginteractions.org/ Evotaz Tenofovir Alafenamide (TAF) • Atazanavir/cobicistat • In phase III trials • One pill once a day, with food • Prodrug of the nucleotide analog tenofovir • Adverse effects • Conversion occurs intracellulary • Elevated bilirubin levels, jaundice, scleral icterus • Lower plasma exposure than tenofovir disoproxil fumarate (TDF) • Diarrhea, nausea, vomiting • Higher active [drug] in mononuclear cells • Increased serum creatinine • Benefits over TDF: • Drug interactions • Less toxicities (nephrotoxicity, BMD/fractures) • CYP-3A4 substrates • Smaller dose required (pill size) • http://www.hiv-druginteractions.org/ 5 ¡

9/30/15 ¡ Question Post Exposure Prophylaxis (PEP) (True/False) All 3 INSTIs are listed as • Last updated 2013 recommended agents in the 2015 DHHS HIV • Elimination of risk stratification for exposure treatment guidelines. incidents • 3-drug PEP regimen for all A. True • Expanded list of ARVs for PEP B. False • Emphasis on tolerability and convenience of PEP regimen • New recommendations for follow-up HIV testing www.aidsetc.org Occupational Risk Exposures Toxicity of PEP Regimens • Percutaneous injury or contact of mucous • Previous PEP boosted PI-based regimens membrane or non-intact skin • GI side effects common • Blood • Major reason for not completing PEP • Tissue • Ritonavir has many drug interactions • Body fluids that are potentially infectious • Tolerability major emphasis for recommended • CSF, synovial, pleural, pericardial, peritoneal, amniotic, semen, PEP vaginal secretions • Potential side effects should be discussed • Not considered infectious:* • Feces, nasal secretions, saliva, sputum, sweat, tears, urine, vomitus * Unless visibly bloody HIV PEP Recommendations Preferred PEP Regimen • Newer agents better tolerated and have better Raltegravir 400 mg BID + Truvada 1 tab QD toxicity profiles than previous agents • 3 or more tolerable agents now recommended for all occupational exposures to HIV • 2 NRTIs (backbone) • 1 INSTI, ritonavir-boosted PI or NNRTI • Other classes may be indicated (resistant virus) • To facilitate completion of PEP • Optimize side effect and toxicity profiles • Optimize dosing convenience 6 ¡

9/30/15 ¡ Alternative PEP Regimens Timing and Duration of PEP 1 from each column • Most effective when begun soon after the exposure in animal studies • Raltegravir • Tenofovir + • Start as soon as possible after the exposure, emtricitabine • Darunavir + ritonavir preferably within hours (72 hours) • Etravirine • Tenofovir + • Point at which no benefit gained not defined • Rilpivirine lamivudine • Duration of PEP is full 4 weeks (28 days) • Atazanavir + ritonavir • Zidovudine + • Lopinavir/ritonavir lamivudine • Stribild* • Zidovudine + • Tivicay # emtricitabine * Single tablet daily # Approved 2013 for treatment of HIV Question Questions Which of the following statements is TRUE regarding occupational exposure HIV PEP? A. The recommended duration of PEP is 2 weeks B. A positive HIV test is required before initiation of PEP C. An ideal PEP regimen includes abacavir + lamivudine backbone D. PEP should be started as soon as possible after exposure E. Dolutegravir is included as part of the preferred PEP regimen 7 ¡