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HIV Therapy Experience is the Best Teacher David K. Stein, M.D.

HIV Therapy Experience is the Best Teacher David K. Stein, M.D. Director, Adult HIV Research Activities Jacobi Medical Center Associate Professor of Clinical Medicine Albert Einstein College of Medicine. But, It’s a Humbling Way to Learn. Lessons I’ve Learned the Hard Way!. Assumptions.

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HIV Therapy Experience is the Best Teacher David K. Stein, M.D.

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  1. HIV Therapy Experience is the Best Teacher David K. Stein, M.D. Director, Adult HIV Research Activities Jacobi Medical Center Associate Professor of Clinical Medicine Albert Einstein College of Medicine

  2. But, It’s a Humbling Way to Learn Lessons I’ve Learned the Hard Way!

  3. Assumptions • Most of you will never take the ID Boards or become Primary Care HIV Providers • Most of you will not be the Primary manager of HIV infected patients • Most of you don’t speak up when a question is asked of the audience in a lecture, even if you know the answer. • I have assurances that even if you answer incorrectly you will probably still have a job tomorrow (although I can’t say what that job will entail) • My kids think I’m crazy, and they probably are right.

  4. LS

  5. What do all those letters and numbers mean? M184M/V Translation = High level resistance to Lamivudine and Emtricitibine

  6. LS Genotypes September 2006 • None February 2005 • K65K/R June 2002 • M41M/L • D67N • K70R • K103N • T215F • K219E October 2007 • D67N • K70R • K103N • T215F • K219E

  7. Let’s Go Back to School

  8. Y=mx + b

  9. 1010

  10. Codon 184 10-5 Normally Methionine ATG to ATA [methionine to isoleucine] and ATG to GTA [methionine to valine]

  11. HAART = Highly Active Anti-Retroviral Therapy HAART typically contains 3 or more ACTIVE drugs

  12. 10-5 X 10-5 X 10-5 = 10-15

  13. Genetic Barrier Different Drugs have different Genetic Barriers

  14. OK, I’ve been sitting here for the last few minutes. What has this got to do with me?

  15. HIVNET 012 Neviripine given for Maternal-Fetal HIV Transmission Prevention

  16. I GOT IT – at least 3 DRUGS BUT 1 can equal 2 or 3 or 4

  17. Drug Combinations • Trizivir 1=3 • Atripla 1=3 • Complera 1=3 • Complere 1=0 • Stribild 1=3+ • Combivir 1=2 • Epzicom 1=2 • Truvada 1=2 • Kaletra 2=1+

  18. Nothing is Not always Nothing

  19. What to do? • Patient comes to ER complaining of stomach upset and nausea after starting a 3 drug combination of Efavirenz, Lamivudine and Zidovudine. He says he is miserable and looks uncomfortable, but not in need of admission. • He was given Zofran and Omeprazole with no relief. • He sees his PMD in 10 days but it is the weekend and he is not in the office today.

  20. T 1/2

  21. A Little Bit of Something can be Dangerous

  22. What is wrong with this? • A patient with HIV, Asthma, and a history of a prior UGI bleed comes to the ER with an acute Asthma attack. She is taking Atazanavir and Epzicom for the last 4 years. Nebs are given and the patient is somewhat better, but needs steroids before discharge. In addition to the Prednisone she is given Omeprazole which she received 3 years ago when she had an UGI bleed.

  23. Click!

  24. Giving a Prescription is not a Treatment • 1 BID is not 2 pills a day • 1 BID is not 1 at Breakfast, 1 at Lunch • In This case 1 or 2 is less than 1

  25. Time to Switch Gears

  26. Sometimes the little things that don’t seem important at the time can save a person’s life • A 27 year old female comes into the ER with burning on urination for the last week. She is otherwise healthy. Her exam is remarkable for some mild tenderness over the bladder. UA is abnormal and she is given some antibiotics for a UTI

  27. 2006 Recommendations From CDC: Routine Opt-Out Testing for HIV • Routine voluntary testing for patients aged 13-64 yrs in healthcare settings—not based on patient risk Branson BM, et al. MMWR Recomm Rep. 2006;55(RR-14):1-17.

  28. Improving Control of HIV Begins With Enhanced Detection and Linkage to Care • Data from CDC and Prevention National HIV Surveillance System used to calculate HIV prevalence, undiagnosed HIV prevalence, and linkage to HIV care N = 1,148,200 100 82% 941,524 80% 80 82% 757,812 60 66% 56% Patients (%) 89% 424,834 40 378,906 75% 37% 287,050 33% 20 25% 0 Diagnosed Linked to Care Retained in Care Prescribed ART Viral Suppression Hall HI, et al. AIDS 2012. Abstract FRLBX05.

  29. When to Start ART • Exact CD4 count at which to initiate therapy not known, but evidence points to starting at higher counts • Current recommendation: ART for all www.aidsetc.org

  30. Potential Benefits of Early Therapy • Untreated HIV may be associated with development of AIDS and non-AIDS-defining conditions • Earlier ART may prevent HIV-related end organ damage; deferred ART may not reliably repair damage acquired earlier • Increasing evidence of direct HIV effects on various end organs and indirect effects via HIV-associated inflammation • End-organ damage occurs at all stages of infection www.aidsetc.org

  31. Risks and Benefits of Earlier Initiation of ART Delayed ART Early ART • Drug toxicity • Preservation of limited Rx options • Risk of resistance (and transmission of resistant virus) • ↑ potency, durability, simplicity, safety of current regimens • ↓ emergence of resistance • ↓ toxicity with earlier therapy • Risk of uncontrolled viremia • Near normal survival if CD4+ count > 500 • ↓ transmission

  32. Current ARV Medications * EVG currently available only in coformulation with cobicistat (COBI)/TDF/FTC www.aidsetc.org

  33. Selected Complications Mitochondrial Toxicity • Lactic Acidosis • Lipoatrophy • Metabolic Syndrome • Cardiac Toxicity? • Nephrotoxicity • Other

  34. All NRTIs: Lactic acidosis and hepatic steatosis (highest incidence with d4T, then ddI and ZDV, lower with TDF, ABC, 3TC, and FTC) Lipodystrophy(higher incidence with d4T) Adverse Effects: NRTIs www.aidsetc.org

  35. All NNRTIs: Rash, including Stevens-Johnson syndrome Hepatotoxicity (especially NVP) Drug-drug interactions Adverse Effects: NNRTIs www.aidsetc.org

  36. All PIs: Hyperlipidemia Lipodystrophy Hepatotoxicity GI intolerance Possibility of increased bleeding riskfor hemophiliacs Drug-drug interactions Adverse Effects: PIs www.aidsetc.org

  37. RAL Nausea Headache Diarrhea CPK elevation, myopathy, rhabdomyolysis Rash Adverse Effects: II www.aidsetc.org

  38. Adverse Effects: CCR5 Antagonist • MVC • Drug-drug interactions • Rash • Abdominal pain • Upper respiratory tract infections • Cough • Hepatotoxicity • Musculoskeletal symptoms • Orthostatic hypotension, especially if severe renal disease www.aidsetc.org

  39. Adverse Effects: Fusion Inhibitor • ENF • Injection-site reactions • HSR • Increased risk of bacterial pneumonia www.aidsetc.org

  40. Opportunistic Infections • PJP • Cryptococcal meningitis • MAC • Cryptosporidiosis • Toxoplasmosis • Esophageal Candidiasis • Histoplasmosis • CMV • TB

  41. Treatment-Experienced Patients: ART Failure • Causes of treatment failure include: • Patient factors (eg, CD4 nadir, pretreatment HIV RNA, comorbidities) • Drug resistance • Suboptimal adherence • ARV toxicity and intolerance • Pharmacokinetic problems • Suboptimal drug potency • Provider experience www.aidsetc.org

  42. HIV Treatment 2013 $2323.84/month $2810/month $2253/month A mere one pill once per day….but at what cost?

  43. Take Home Message 3 Unless 1or 2 = 3

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