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Antiretroviral therapy and Primary Care

Antiretroviral therapy and Primary Care. Chris Boyle, MD 9/8/2011. Case.

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Antiretroviral therapy and Primary Care

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  1. Antiretroviral therapy and Primary Care • Chris Boyle, MD • 9/8/2011

  2. Case • 56 yo man tests positive for HIV after you initiate routine HIV testing during your first clinic visit. He feels well. He has a PMH of hyperlipidemia, GERD and seasonal allergies. He is highly motivated to initiate ARVs. Do you • a) Refer him to a HIV specialist • b) Take care of him yourself.

  3. Katz, MH. Human Immunodeficiency Virus Is (Once Again) a Primary Care Disease. Arch Intern Med. 2011;171(8):719-720.

  4. HIV Screening and Access to Care: Health Care System Capacity for Increased HIV Testing and Provision of Care (2011) • “Increased use of strategies such as task shifting, comanagement, and care coordinationcan help to maximize the ability of the current health care workforce to accommodate an increased number of HIV-positive individuals. In addition, these strategies may result in improved patient care and increased provider satisfaction, which, in turn, may increase the retention of HIV/AIDS care providers in the field.” • “...the emergence of HIV as a chronic medical condition...infectious disease specialists and primary care providers who are HIV experts due to substantial patient care experiences, formal training, or both, are generally better-prepared to manage HIV disease than are primary care generalists....However, most HIV-positive patients can benefit greatly from the broader skills of primary care providers in addressing their other health care needs.” Committee on HIV Screening and Access to Care; Institute of Medicine. “HIV Screening and Access to Care: Health Care System Capacity for Increased HIV Testing and Provision of Care.” The National Academies Press, 2011.

  5. Case • 56 yo man tests positive for HIV after you initiate routine HIV testing during your first clinic visit. He feels well. He has a PMH of hyperlipidemia, GERD and seasonal allergies. He is highly motivated to initiate ARVs. • You keep him!

  6. Case • 56 yo man tests positive for HIV after you initiate routine HIV testing during your first clinic visit. He feels well. He has a PMH of hyperlipidemia, GERD and seasonal allergies. He is highly motivated to initiate ARVs. You check HIV intake labs, including a CD4, viral load and resistance panel. Labs are significant for a CD4=496 and VL=6500, with wild type virus.

  7. When to Start • 56 yo man tests positive for HIV after you initiate routine HIV testing during your first clinic visit. He feels well. He has a PMH of hyperlipidemia, GERD and seasonal allergies. He is highly motivated to initiate ARVs. You check HIV intake labs, including a CD4, viral load and resistance panel. Labs are significant for a CD4=496 and VL=6500, with wild type virus. • a) Initiate ARVs - everyone should be on treatment • b) Initiate ARVs - His CD4 count is <500 • c) Do not initiate ARVs until his CD4 is <350 • d) Do not initiate ARVs until his CD4 count is <200 • e) Do not initiate ARVs until he has an opportunistic infection

  8. When to Start • There are two major organizations that periodically make updates regarding when and what to start. • The Department of Health and Human Services (DHHS) - last updated in 01/2011 and The International Antiviral Society - USA (IAS-USA) - last updated in 07/2010

  9. When to Start • Historical Perspective • 1996 - treat for a CD4<500, consider treatment in all • Mantra “Hit Early, Hit Hard”(N Engl J Med. 1995;333(7):450.) • however drugs had multiple side effects, difficult to adhere to regimens, which led to... • 2001 - treat for a CD4<200 and consider treatment if 200-350 • however regimens became better tolerated, easier to administer and there was increasing evidence that treating earlier improved mortality, which led to... • 2007 - treat for a CD4<350, several caveats of when to treat earlier • 2009 - treat for a CD4<500, consider treatment in all.

  10. When to Start - 2011 • Cohort study from 1996-2004 using a large data registry with 3,851 HIV and 1,044,589 non-HIV patients at Brigham and Women’s Hospital (BWH) or Massachusetts General Hospital (MGH) • The primary outcome was myocardial infarction, identified by International Classification of Diseases coding criteria J Clin Endocrinol Metab. 2007 Jul;92(7):2506-12

  11. When to Start - 2011 A, Myocardial infarction rates and corresponding adjusted RR. HIV Non-HIV J Clin Endocrinol Metab. 2007 Jul;92(7):2506-12

  12. When to Start - 2011 Patel P, et al. Incidence of Types of Cancer among HIV Infected Persons Compared with the General Population in the United States, 1992–2003. Ann Intern Med. 2008;148:728-736.

  13. When to Start - 2011 SMART • Randomized controlled study evaluating continuous use of antiretroviral therapy vs scheduled drug interruptions in management of HIV • 5472 participants with 2720 assigned to drug conservation (scheduled interruptions) and 2752 to viral suppression arms (continuous therapy) • Medial CD4 count at entry was 597. • The primary end point was the development of an opportunistic disease or death from any cause. • The secondary end point was major cardiovascular, renal, or hepatic disease. El-Sadr WM, et al. CD4+ Count–Guided Interruption of Antiretroviral Treatment The Strategies for Management of Antiretroviral Therapy (SMART) Study Group. N Engl J Med 2006;355:2283-96.

  14. El-Sadr WM, et al. CD4+ Count–Guided Interruption of Antiretroviral Treatment The Strategies for Management of Antiretroviral Therapy (SMART) Study Group. N Engl J Med 2006;355:2283-96.

  15. Whn to Start - 2011 El-Sadr WM, et al. CD4+ Count–Guided Interruption of Antiretroviral Treatment The Strategies for Management of Antiretroviral Therapy (SMART) Study Group. N Engl J Med 2006;355:2283-96.

  16. When to Start - 2011 The HIV-CAUSAL Collaboration Art-CC NA-ACCORD N Engl J Med. 2009 Apr 30;360(18):1815-26 Lancet. 2009 Apr 18;373(9672):1352-63. Ann Intern Med. 2011 Apr 19;154(8):509-15.

  17. When to Start - 2011 NA-ACCORD • Observational study of 17,517 asymptomatic HIV infected patients in the United States and Canada from1996 through 2005. • All patients were ARV naive and were stratified according to the CD4, either >500 or 351-499 at initiation or ARVs. • Primary endpoint was relative risk of death for patients who initiated treatment with those that deferred. N Engl J Med. 2009 Apr 30;360(18):1815-26

  18. When to Start - 2011 N Engl J Med 2009;360:1815-26

  19. When to Start - 2011 N Engl J Med. 2009 Apr 30;360(18):1815-26

  20. When to Start - 2011 N Engl J Med. 2009 Apr 30;360(18):1815-26

  21. When to Start - 2011 HPTN - 052 • Multi-national randomized controlled trial which enrolled 1763 ART naïve HIV positive patients with CD4 counts of 350-500 who were in sero-discordant couples. • The primary end point was linked HIV transmission in HIV negative partners. • Study halted early, and data analyzed found that early initiation of ART had a 96% relative reduction in linked HIV transmissions N Engl J Med 2011; 365:493-505

  22. DHHS guidelines • ss Department of Health and Human Services, 2011

  23. What to Start • 56 yo man tests positive for HIV after you initiate routine HIV testing during your first clinic visit. He feels well. He has a PMH of hyperlipidemia, GERD and seasonal allergies. He is highly motivated to initiate ARVs. You check HIV intake labs, including a CD4, viral load and resistance panel. Labs are significant for a CD4=496 and VL=6500, with wild type virus. • You review his HIV genotype and he has wild type virus. What do you want to start? • a) Tenofovir + Emtricitabine (Truvada) + Lopinavir/Ritonavir (Kaletra) • b) Abacavir + Lamivudine (Epzicom) + Atazanavir/Ritonavir • c) Combination Tenofovir + Emtricitabine + Efavirenz (Atripla) • d) Combination abacavir, zidovudine, lamivudine (Trizivir)

  24. What to Start http://depts.washington.edu/nwaetc/Pill_Chart_2010.pdf

  25. http://depts.washington.edu/nwaetc/Pill_Chart_2010.pdf

  26. + Rilpivirine http://depts.washington.edu/nwaetc/Pill_Chart_2010.pdf

  27. What to Start Combination NRTIs Protease Inhibitors NNRTIs Integrase Inhibitors http://depts.washington.edu/nwaetc/Pill_Chart_2010.pdf

  28. What to Start • Concepts in antiretroviral treatment • Always have three active drugs • Whenever possible those should include a “preferred” or “alternative” regimen which includes • 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) AND • 1 active protease inhibitor (PI), non-nucleoside reverse transcriptase inhibitor (NNRTI), or an integrase inhibitor • NOTE: Protease inhibitors should almost always be co-administered with ritonavir

  29. What to Start • DHHS graphic of the Preferred and alternative regimens Department of Health and Human Services, 2011

  30. Thompson, M.A. et al. JAMA 2010;304:321-333

  31. + or or with = HAART http://depts.washington.edu/nwaetc/Pill_Chart_2010.pdf

  32. What to Start • Choosing a regimen • 1) Based on resistance profile • 2) Prior ARV exposure • 3) side effects • 4) pill burden • 5) potential drug-drug interactions • 6) patient co-morbidities

  33. What to Start • 56 yo man tests positive for HIV after you initiate routine HIV testing during your first clinic visit. He feels well. He has a PMH of hyperlipidemia, GERD and seasonal allergies. He is highly motivated to initiate ARVs. You check HIV intake labs, including a CD4, viral load and resistance panel. Labs are significant for a CD4=496 and VL=6500, with wild type virus. • ...you discuss his options as TDF/FTC/EFV (Atripla), TDF/FTC (Truvada) + Atazanavir/ritonavir, TDF/FTC (Truvada) + Darunavir/ritonavir, and TDF/FTC (Truvada) + Raltegravir. He prefers a once-a-day regimen, but doesn’t otherwise care if he has to take multiple pills. He is worried about that pill that makes you “go crazy”.

  34. What to Start • ...you probe his PMH a bit more and find out that his GERD quite severe and is taking daily Omeprazole and he is on Simvastatin 40mg PO daily for an LDL of 160 with multiple CAD risk factors. • What do you choose? • a) Tenofovir + Emtricitabine (Truvada) + Atazanavir/Ritonavir • b) Tenofovir + Emtricitabine (Truvada) + Darunavir/Ritonavir • c) Combination Tenofovir + Emtricitabine + Efavirenz (Atripla) • d) Tenofovir + Emtricitabine (Truvada) + Raltegravir

  35. Side effects • 58 yo woman with pancreatitis, neuropathy, lipodystrophy and lactic acidosis. What ARV is she on? • Stavudine or didanosine (no longer used in the US, or most of the world)

  36. Side effects • 30 yo man on ARVs with an elevated creatinine seen on routine labs. What ARV is he on? • Tenofovir • renal insufficiency (0.5% of patients) • fanconi syndrome

  37. Side effects • 23 yo woman who started ARVs two weeks ago and now feels “flu-ish”, along with diarrhea, nausea, vomiting and new dyspnea on exertion for the past week. Also for the past 2 days she has noticed a new rash. On exam she has a fever to 39.5 celsius and blood pressure of 95/50 (baseline is 120/75). What ARV is she on? • Abacavir • Abacavir hypersensitivity (3-5% of patients) • screen with HLA-B*5701 testing prior to initiation • also caution in patients with CAD or CAD risk factors

  38. Side effects • NRTIs • lactic acidosis (very very very rare with current NRTIs …mostly from stavudine, didanosine and AZT) • nausea/vomiting • HBV flare if discontinued • Abacavir • Abacavir hypersensitivity (3-5% of patients) • screen with HLA-B*5701 testing • also caution in patients with CAD or CAD risk factors • Tenofovir • fanconi syndrome • renal insufficiency (0.5% of patients) • Stavudine and didanosine (no longer used in the US, or most of the world) • pancreatitis • lactic acidosis • lipodystrophy • neuropathy

  39. Side effects • 28 yo man whose skin looks like this. What ARV is he on? • Atazanavir • commonly causes an indirect hyperbilirubinemia • rarely causes jaundice • entirely harmless and goes away with discontinuation http://optimismandwhitepaint.blogspot.com/2009/08/house-beautiful-color-quiz.html

  40. Side effects • 34 yo man started on ARVs 2 weeks ago who has been hanging out with this guy for the past 10 days.

  41. Side effects What class of ARVs is he on? http://horizoncomfortzone.blogspot.com/2011/01/amazing-toilet-facts.html

  42. Side effects • PIs (all cause nausea, vomiting and diarrhea and dyslipidemia) • Atazanavir • jaundice (elevated indirect bilirubinemia) • excellent lipid profile • Darunavir • caution in sulfa allergic patients • excellent lipid profile • Ritonavir • reputation for bad nausea, vomiting, diarrhea

  43. Side effects • 56 yo man started on ARVs 6 months ago. Since starting ARVs he has had nightly vivid nightmares. Additionally he now feels kind of depressed. What ARV is he on? • Efavirenz

  44. Side effects • NNRTIs • Efavirenz • headaches, nightmares, depression/mood disorders, feeling "hung over" or "disassociated" (23% will have some CNS effects; generally goes away with time) • rash (up to 25%, usually goes away) • dyslipidemia • hepatotoxicity • teratogenic (neural tube disorders), don’t use in the first trimester • Nevirapine • hepatic necrosis (idiosyncratic, and increased risk at higher CD4 counts)

  45. Side effects • 45 year old man recently started on ARVs and is experiencing no side effects, but is realizing that twice daily meds is harder than expected • Raltegravir • very well tolerated • occasional nausea, vomiting, headache, diarrhea, but usually no side effects. • BID dosing

  46. Drug-Drug Interactions • 1) Acid suppressants • 2) Anticonvulsants • 3) Statins • 4) TB medications • 5) Methadone • 6) Antidepressants • 7) Oral Contraceptives

  47. Drug-Drug Interactions • 1) Acid suppressants • atazanavir requires a acidic environment and should not be coadministered with a PPI and should be separated from a H2 blocker by 12 hours

  48. Drug-Drug Interactions • Antidepressants – Interact with protease inhibitors, and NNRTIs and generally DECREASE antidepressant levels. • Bupropion + Efavirenz (decreases bupropion) • Sertraline + Efavirenz (decreases sertraline) • Paroxetine + Darunavir/r (decreases paroxetine) • Sertraline + Darunavir/r (decreases sertraline) • Trazadone + all ritonavir boosted PIs (increases trazadone) • TCAs + all ritonavir boosted PIs (increases TCA)

  49. Drug-Drug Interactions • Anticonvulsants • Phenytoin - DO NOT use with PIs or NNRTIs (decreases ARV serum levels) • Carbamezapine - DO NOT use with Pis (decreases ARV serum levels) • Lamotrigine - Avoid with PIs (decreases lamotrigine drug levels)

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