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2012 HIV Update

2012 HIV Update. David Spach, MD Clinical Director, Northwest AETC Professor of Medicine, Division of Infectious Diseases University of Washington. Presentation Prepared by: David Spach, MD Last Updated: April 16 , 2012. 2012 HIV Clinical Update: Topics . Acute (Primary) HIV Infection

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2012 HIV Update

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  1. 2012 HIV Update David Spach, MDClinical Director, Northwest AETCProfessor of Medicine, Division of Infectious DiseasesUniversity of Washington Presentation Prepared by: David Spach, MDLast Updated: April 16, 2012

  2. 2012 HIV Clinical Update: Topics • Acute (Primary) HIV Infection • 2012 HHS Antiretroviral Therapy Guidelines • Recognizing Common Clinical Manifestations • Healthcare Postexposure Prophylaxis

  3. HIV 2012 Update Acute HIV

  4. A 22-Year-Old Man with a Flu-Like Illness • A 22-year-old man is seen in the urgent care clinic with a 3-day history of fever, sore throat, headache, myalgias, and fatigue. In addition, for one day he has a diffuse maculopapular, erythematous rash. He had anonymous sex with 2 men about 3 weeks ago.

  5. Morbilliform Rash Photograph from David Spach, MD

  6. A 22-Year-Old Man with a Flu-Like Illness • What is in your differential diagnosis? • What tests would you order?

  7. PRIMARY (ACUTE) HIV Clinical Manifestations of Primary HIV Infection N =160 From: Vanhems P, et al. AIDS. 2000;14:375-81.

  8. Acute (Primary) HIV: Eclipse Phase Eclipse Phase HIV RNA Limit of Detection Eclipse Phase = Time between infection and detectable HIV RNA

  9. Acute (Primary) HIV: Window Period Window Period Window Period = Time between infection and detectable HIV antibodies

  10. PRIMARY (ACUTE) HIV Acute (Primary) HIV: Symptomatic Disease Acute Illness Symptomatic Disease Often Precedes Positive Antibody Test

  11. Transmission of HIV HIV + -

  12. Transmission of HIV Chronic HIV infection Quasispecies HIV-Negative + -

  13. Transmission of HIV: Founder Virus Chronic HIV infection Quasispecies New Infected with HIV Founder Virus + +

  14. Acute (Primary) HIVHigh Transmission Risk +

  15. Acute (Primary) HIVFactors Associated with High Transmission Risk • Unaware of HIV status • High “viral load” • Homogeneity of transmission-capable viral variants • Low titer of neutralizing antibodies - - - + - - -

  16. HIV 2012 Update HHS Antiretroviral Therapy Recommendations

  17. US Health and Human Services (HHS) March 27, 2012 Antiretroviral Therapy Guidelines Source: 2012 HHS Antiretroviral Therapy Guidelines. AIDS Info (www.aidsinfo.nih.gov)

  18. Case History • A 28-year-old man was diagnosed with HIV about 18 months ago. She is seen in the clinic for follow up. His CD4 counts have been 770, 710, 640, and 610 cells/mm3. He has no active medical, mental health, or substance abuse issues. He is sexually active with other men and uses condoms most of the time. • Would you recommend starting antiretroviral therapy?

  19. ANTIRETROVIRAL THERAPY: HHS GUIDELINES HHS Antiretroviral Therapy Guidelines: March 2012Initiating Therapy in Treatment-Naïve Patients Recommend: Moderate (BIII) 500 Recommend: Strong (AII) 350 Recommend: Strong (AII) Source: 2012 HHS Antiretroviral Therapy Guidelines. AIDS Info (www.aidsinfo.nih.gov)

  20. ANTIRETROVIRAL THERAPY: HHS GUIDELINES Initiating Antiretroviral Therapy in Treatment-Naïve PatientsChange in CD4 Threshold in HHS Guidelines 2012 2009 500 2007 350 2003 200

  21. ANTIRETROVIRAL THERAPY: HHS GUIDELINES HHS Antiretroviral Therapy Guidelines: March 2012 Initiating Therapy in Treatment-Naïve Patients Earlier Therapy LaterTherapy

  22. Initiating Antiretroviral Therapy Why are we treating earlier with antiretroviral therapy?

  23. ANTIRETROVIRAL THERAPY: HHS GUIDELINES HHS Antiretroviral Therapy Guidelines: March 2012 Factors Affecting Decision on When to Initiate Therapy • More effective regimens • More convenient regimens • Better tolerated therapy • Less long-term toxicity • Better immune recovery • Lower rates of resistance • More treatment options • Concerns for uncontrolled viremia • Decrease HIV transmission • Lack of RCT data supporting early Rx • Potential drug toxicity • Drug and monitoring cost • Potential negative impact on QOL LaterTherapy Earlier Therapy

  24. PREVENTION OF OPPORTUNISTIC INFECTIONS CD4 Cell Progression (without Antiretroviral Therapy) AIDS Year 1

  25. Chronic Immune Activation and Inflammation Immune Activation & Inflammation Year 1(expanded)

  26. ANTIRETROVIRAL THERAPY Attributable Risk Factors Associated with Cardiovascular Disease EventsHOPS Study, January 2002–September 2009 Cox Proportional Hazards: Relationship of Baseline CD4 and Risk of Subsequent Cardiovascular Events N = 2,005 Source: Lichtenstein KA, et al. Clin Infect Dis. 2010;51:435-47.

  27. ANTIRETROVIRAL THERAPY: DHHS GUIDELINES Attributable Risk Factors Associated with Cardiovascular Disease EventsHOPS Study, January 2002–September 2009 N = 2,005 Source: Lichtenstein KA, et al. Clin Infect Dis. 2010;51:435-47.

  28. Chronic InflammationImpact on HIV-Infected Persons • Increased risk of heart disease • Increased risk of stroke • Increased risk of cancer

  29. HIV Prevention Trials Network (HPTN) Study 052 1,763 HIV Serodiscordant Couples (97% heterosexual) + - + - + - + - n = 872 n = 853 n = 37 n = 1 Source: Cohen M, et al. N EnglJ Med. 2011;36:493-505.

  30. ANTIRETROVIRAL THERAPY: DHHS GUIDELINES HIV Prevention Trials Network (HPTN) Study 052 550 Early TherapyCD4 350-550 cells/mm3 350 250 Deferred TherapyCD4 < 250 cells/mm3 or AIDS Related Event Source: Cohen M, et al. N Engl J Med. 2011;36:493-505.

  31. HIV Prevention Trials Network (HPTN) Study 052 96% Reduction P < 0.001 Source: Cohen M, et al. N Engl J Med. 2011;36:493-505.

  32. DHHS Antiretroviral Therapy Guidelines: October 2011 Preferred Regimens for ARV-Naïve Patients: Pill Burden Source: 2011 DHHS Antiretroviral Therapy Guidelines. AIDS Info (www.aidsinfo.nih.gov)

  33. ANTIRETROVIRAL THERAPY: HHS GUIDELINES HHS Antiretroviral Therapy Guidelines: March 2012 Preferred Regimens for ARV-Naïve Patients: Pill Burden *AWP = average wholesale price Source: 2012 HHS Antiretroviral Therapy Guidelines. AIDS Info (www.aidsinfo.nih.gov)

  34. 2011: New FDA-Approved HIV Medications (or New Preparations of Older Medications) • Nevirapine XR (Viramune XR): 400 mg tablet • Etravirine (Intelence): 200 mg tablet • Rilpivirine (Edurant): 25 mg tablet • Tenofovir-Emtricitabine-Rilpivirine (Complera): 1 pill qd

  35. Case History • A 30-year-old woman with asymptomatic HIV infection is seen for follow-up in the clinic to discuss starting antiretroviral therapy. She states she really wants to take the the “one pill a day” regimen. She has no other medical problems. • Most recent labs show a CD4 cell count of 375 cells/mm3and CD4% = 16. Most recent HIV RNA is 65,300 copies/ml. A baseline genotype shows no mutations. • Which one pill once a day regimen to give her?

  36. AtriplaversusComplera Atripla Complera Tenofovir-Emtricitabine-Efavirenz Tenofovir-Emtricitabine-Rilpivirine NNRTI NNRTI NRTI NRTI NRTI NRTI Image Source: AIDS Info.org

  37. Rilpivirine vs. Efavirenz in ARV-Naive ECHO and THRIVE Pooled Data: Study Design Rilpivirine: 25 mg qd + TDF/FTC(n = 346) ECHO 1x Efavirenz: 600 mg qd + TDF/FTC(n = 344) Rilpivirine: 25 mg qd + 2NRTIs(n = 340) THRIVE 1x Efavirenz: 600 mg qd + 2NRTIs(n = 338) *2 NRTIs: ECHO: Tenofovir + Emtricitabine (TDF/FTC)THRIVE: Tenofovir + Emtricitabine; Zidovudine+ Lamivudine; Abacavir + Lamivudine Source: Cohen C, et al. JAIDS. 2012:Feb 16 [Epub ahead of print].

  38. Rilpivirine vs. Efavirenz in ARV-Naive ECHO and THRIVE Pooled Data: Week 48 Results Virologic Response ( ITT-TLOVR) over 48 Weeks 84% 82% 2NRTIs+ Rilpivirine (n = 686) 2NRTIs+ Efavirenz (n = 682) Source: Cohen C, et al. JAIDS. 2012:Feb 16 [Epub ahead of print].

  39. Rilpivirine vs. Efavirenz in ARV-Naive ECHO and THRIVE: Virologic Failure Results Virologic Failure 48 Week Data All regimens included 2 NRTIs Source: Rimsky L, et al. JAIDS. 2012;59:39-46.

  40. 2012 HIV Update Recognizing Clinical Manifestations

  41. Cutaneous Manifestations

  42. CLINICAL MANIFESTATIONS Case History

  43. CLINICAL MANIFESTATIONS Case History

  44. CLINICAL MANIFESTATIONS Case History

  45. CLINICAL MANIFESTATIONS Case History

  46. CLINICAL MANIFESTATIONS Case History

  47. CLINICAL MANIFESTATIONS Case History

  48. CLINICAL MANIFESTATIONS Case History

  49. CLINICAL MANIFESTATIONS Case History

  50. Oral Manifestations

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