1. Kimberly Y. Smith, MD, MPH Associate Professor of Medicine Division of Infectious Diseases Rush University Medical Center Chicago, Illinois Putting the DHHS HIV Treatment Guidelines Into Practice This program is supported by an educational grant from Jointly sponsored by Annenberg Center for Health Sciences at Eisenhower and Clinical Care Options, LLC

2. Clinical Focus: 2012 DHHS Guideline Update clinicaloptions.com/hiv Faculty Disclosures Kimberly Y. Smith, MD, MPH, has disclosed that she has received consulting fees from Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Janssen, Merck, and ViiV.

3. Clinical Focus: 2012 DHHS Guideline Update clinicaloptions.com/hiv Key Updates in 2012 DHHS Guidelines  Timing of ART initiation in treatment-naive patients  Treatment as prevention  Guidance on new regimens  Considerations for older patients  Considerations for HIV-infected women of childbearing age  Coadministration of antiretrovirals and HCV protease inhibitors  Timing of ART initiation in patients with TB

4. Clinical Focus: 2012 DHHS Guideline Update clinicaloptions.com/hiv  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 Early ARTDelayed ART Risks and Benefits of Earlier Initiation of ART

5. Science has given us the tools we need to dramatically change the course of the HIV/AIDS pandemic and ultimately end AIDS Now these tools must be applied Anthony S. Fauci Director, NIAID

6. Clinical Focus: 2012 DHHS Guideline Update clinicaloptions.com/hiv Guidelines Moving Toward Early Treatment  Early diagnosis, timely treatment can change the course of the epidemic  Changes to guidelines reflect these goals –Evolution toward treatment of essentially all patients –Inclusion of treatment as prevention

7. Clinical Focus: 2012 DHHS Guideline Update clinicaloptions.com/hiv CD4+ Count, cells/mm 3 199820012006200820092012 > 500 Offer if VL > 20,000 Offer if VL > 55,000 Consider if VL ≥ 100,000 Consider in certain groups ConsiderTreat 350-500 Offer if VL > 20,000 Consider if VL > 55,000 Consider if VL ≥ 100,000 Consider in certain groups Treat 200-350 Offer if VL > 20,000 Offer, but controversy exists Offer after discussion with patient Treat < 200 or symptomatic disease Treat DHHS: Changing Criteria for Initiating ART

8. Clinical Focus: 2012 DHHS Guideline Update clinicaloptions.com/hiv GuidelineSymptomatic/ AIDS CD4+ Count < 200 CD4+ Count 200-350 CD4+ Count 350-500 CD4+ Count > 500 DHHS (2/2012)Yes IAS-USA (7/2012) Yes British HIV Association (9/2012) Yes Defer* European AIDS Clinical Society (11/2012) Yes ConsiderDefer WHO (7/2010)Yes No † Not addressed *If a patient with CD4+ count > 350 cells/mm³ wishes to start ART to reduce the risk of transmission to partners, that wish should be respected and ART started. † With the exception of an HIV-positive partner in a serodiscordant relationship, who should be offered antiretroviral therapy at CD4+ count > 350 cells/mm³ to prevent transmission to the uninfected partner. Current Guidelines for Initiating ART

9. Clinical Focus: 2012 DHHS Guideline Update clinicaloptions.com/hiv When to Start ART: 2012 DHHS Guidelines  ART recommended for all HIV-infected patients  Strength of recommendation varies by baseline CD4+ count –< 350 cells/mm 3 (AI) –350-500 cells/mm 3 (AII) –> 500 cells/mm 3 (BIII)  Regardless of CD4+ count, ART strongly recommended if –Pregnancy (AI) –History of an AIDS-defining illness (AII) –HIV-associated nephropathy (AII) –HBV coinfection (AII)  ART recommended for most HCV-coinfected patients DHHS Guidelines for Antiretroviral Therapy in Adults and Adolescents. March 2012.

10. Clinical Focus: 2012 DHHS Guideline Update clinicaloptions.com/hiv  ART should be offered to pts at risk of transmitting HIV to sexual partners, including heterosexuals (AI) and other risk groups (AIII) [6]  HPTN 052 [7] –1763 heterosexual serodiscordant couples in resource-constrained countries randomized to start ART early (CD4+ count 350-550 cells/mm 3 ) or defer until CD4+ count < 250 cells/mm 3 6. DHHS Guidelines for Antiretroviral Therapy in Adults and Adolescents. March 2012. 7. Cohen M, et al. N Engl J Med. 2011;365:493-505. Type of EventEvent Rate/100 PY (95% CI)HR (95% CI) P Value Early ARTDeferred ART Transmission0.3 (0.1-0.6) 2.2 (1.6-3.1) 0.11 (0.04-0.32) <.001 Clinical event2.4 (1.7-3.3) 4.0 (3.5-5.0) 0.59 (0.40-0.88) <.001 When to Start: Treatment as Prevention

11. Clinical Focus: 2012 DHHS Guideline Update clinicaloptions.com/hiv 9. DHHS Guidelines for Antiretroviral Therapy in Adults and Adolescents. March 2012. 10. DHHS Panel Statement. September 18, 2012. DHHS Recommended Regimens [9] NNRTI based  EFV/TDF/FTC Boosted PI based  ATV/RTV + TDF/FTC  DRV/RTV + TDF/FTC INSTI based  RAL + TDF/FTC DHHS Alternative Regimens [9] NNRTI based  EFV + ABC/3TC  ‡  RPV/TDF/FTC or RPV + ABC/3TC* Boosted PI based  DRV/RTV + ABC/3TC  FPV/RTV + (TDF/FTC or ABC/3TC]  LPV/RTV ‡ + (TDF/FTC or ABC/3TC  ) INSTI based  RAL + ABC/3TC  ‡  EVG/COBI/TDF/FTC §[10] *ZDV/3TC is an alternative NRTI component of NNRTI-, PI/RTV-, and RAL-based regimens, but the toxicity profile of ZDV reduces its utility. † In HLA-B*5701–negative patients with baseline HIV-1 RNA < 100,000 copies/mL. ‡ Avoiding the use of ABC or LPV/RTV might be considered for patients with or at high risk of cardiovascular disease. § In patients with creatinine clearance > 70 mL/min. DHHS Guidelines, 2012: What to Start

12. Clinical Focus: 2012 DHHS Guideline Update clinicaloptions.com/hiv  EVG/COBI/TDF/FTC recommended as “alternative” regimen in treatment- naive patients with ClCr > 70 mL/min (BI) [13]  Benefits –Noninferior to EFV/TDF/FTC, [14] ATV/RTV + TDF/FTC [15] –1-tablet, once-daily dosing  Limitations –Potential for drug–drug interactions –Limited safety data; limited data in advanced disease, women –Possible increased risk proximal renal tubulopathy –Food requirement 13. DHHS Panel Statement. September 18, 2012. 14. Sax PE, et al. Lancet. 2012;379:2439-2448. 15. DeJesus E, et al. Lancet. 2010;379:2429-2438. EVG/COBI/TDF/FTC: “Alternative” First-line Regimen

13. Clinical Focus: 2012 DHHS Guideline Update clinicaloptions.com/hiv  ART is recommended in patients older than 50 yrs of age, regardless of CD4+ count (BIII) [16]  Older patients more likely to have comorbidities  Higher rates of comorbidities in HIV-infected vs uninfected patients, including [17] –Cardiovascular disease –Diabetes –Bone fractures –Renal failure 16. DHHS Guidelines for Antiretroviral Therapy in Adults and Adolescents. March 2012. 17. Guaraldi G, et al. Clin Infect Dis. 2011;53:1120-1126. HIV and Patients of Advanced Age or With Comorbid Conditions

14. Clinical Focus: 2012 DHHS Guideline Update clinicaloptions.com/hiv ART Considerations in Older Patients or Those With Comorbidities  Comorbidities can affect ART regimen selection and tolerability  Examples –High cholesterol → avoid lipid-elevating regimens –Cardiovascular disease → may consider avoiding abacavir –Diabetes → may avoid tenofovir DF or boosted PIs –Fragile bones → avoid tenofovir DF –Renal failure → avoid fixed-dose combinations; consider avoiding tenofovir DF 18. DHHS Guidelines for Antiretroviral Therapy in Adults and Adolescents. March 2012.

15. Clinical Focus: 2012 DHHS Guideline Update clinicaloptions.com/hiv Preventing HIV Transmission While Attempting Conception  Inform HIV-infected women of options to prevent sexual transmission of HIV while attempting conception  Possible interventions –Start maximally suppressive ART –Consider PrEP in discordant couples –Artificial insemination, including self-insemination  Counsel about reproductive issues on an ongoing basis 24. DHHS Guidelines for Antiretroviral Therapy in Adults and Adolescents. March 2012. 25. DHHS Perinatal Guidelines. July 2012.

16. Clinical Focus: 2012 DHHS Guideline Update clinicaloptions.com/hiv Management of HIV/HCV Coinfection  ART recommended in most HIV/HCV-coinfected pts (BII), including pts with high CD4+ counts or cirrhosis –HIV treatment-naive pts with CD4+ count > 500 cells/mm 3 may defer ART until completion of HCV therapy –Some clinicians defer HCV therapy in coinfected patients with minimal or no liver fibrosis  For pts both HIV and HCV therapy, recommended initial ART usually same as for non-HCV-infected pts –However, interactions among several antiretrovirals and boceprevir, telaprevir –HCV regimen should guide choice of ART regimen 27. DHHS Guidelines for Antiretroviral Therapy in Adults and Adolescents. March 2012.

17. Clinical Focus: 2012 DHHS Guideline Update clinicaloptions.com/hiv Management of HCV Therapy in HIV/HCV-Coinfected Patients  Recommendations still evolving; important to stay up-to- date in the evolving field of HCV therapy 28. DHHS Guidelines for Antiretroviral Therapy in Adults and Adolescents. March 2012. Patient PopulationHCV Therapy Recommendation Patients not on ARTUse either boceprevir or telaprevir Patients receiving RAL + 2 NRTIsUse either boceprevir or telaprevir Patients receiving ATV/RTV + 2 NRTIs Use telaprevir at standard dose. Do not use boceprevir Patients receiving EFV + 2 NRTIs Use telaprevir at increased dose of 1125 mg every 7-9 hrs; do not use boceprevir

18. Clinical Focus: 2012 DHHS Guideline Update clinicaloptions.com/hiv DHHS Guidelines for Initiating ART in TB-Coinfected Patients Clinical ScenarioRecommendation CD4+ count < 50 cells/mm 3 Start ART within 2 wks of starting TB therapy CD4+ count ≥ 50 cells/mm 3 with clinical disease of major severity* Start ART within 2-4 wks of starting TB therapy Other patients with CD4+ count ≥ 50 cells/mm 3 Can delay ART initiation until 8-12 wks after starting TB therapy Drug-resistant TBStart ART within 2-4 wks after confirmation of resistance, initiation of second-line TB therapy HIV-infected pregnant women with active TB Start ART as early as feasible 32. DHHS Guidelines for Antiretroviral Therapy in Adults and Adolescents. March 2012. *Low Karnofsky score, low body mass index, low hemoglobin, low albumin, organ system dysfunction, extent of disease

19. Clinical Focus: 2012 DHHS Guideline Update clinicaloptions.com/hiv Summary: Key Updates to DHHS Treatment Guidelines  Recommendation to treat all HIV-infected pts  Offer treatment to prevent transmission to uninfected partners  EVG/COBI/TDF/FTC added as a “alternative” first-line regimen  Guidance for use of HCV PIs in HIV/HCV-coinfected pts  Update on preventing transmission while attempting conception  Recommendation to start ART early in selected HIV/TB-coinfected pts

20. Go Online for More Information on Putting the 2012 DHHS Guidelines Into Practice Clinical Focus Concise online CME-certified module with large slide thumbnails paired with supporting text discussion by Dr Smith, and interactive polling questions clinicaloptions.com/DHHSguidelines