2. Jointly Sponsored by: and Clinical Context: HIV/AIDS in Practice Expert Commentary

3. This activity is supported by an independent educational grant from Bristol-Myers Squibb. Clinical Context: HIV/AIDS in Practice Expert Commentary

4. HIV/AIDS in Practice Clinical Context Series The goal of this series is to provide up-to- date information and multiple perspectives on the pathogenesis, symptoms, risk factors, and complications of HIV/AIDS, as well as current and emerging treatments and best practices in the management of HIV/AIDS.

5. HIV/AIDS in Practice Clinical Context Series Target Audience HIV/AIDS specialists, virologists, infectious disease specialists, primary care physicians, nurses, nurse practitioners, physician assistants, pharmacists, and other healthcare professionals involved in the management of HIV/AIDS

6. Activity Learning Objective

7. Statement of Accreditation Statement of Accreditation This activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of Projects In Knowledge and MedPage Today. Projects In Knowledge is accredited by the ACCME to provide continuing medical education for physicians. CME Information: Physicians

8. Credit Designation Credit Designation Projects In Knowledge designates this educational activity for a maximum of 0.5 AMA PRA Category 1 Credits.™ Physicians should claim only the credit commensurate with the extent of their participation in the activity. CME Information

9. Credit for Family Physicians Credit for Family Physicians MedPage Today "News-Based CME" has been reviewed and is acceptable for up to 2098 Elective credits by the American Academy of Family Physicians. AAFP accreditation begins January 1, 2011. Term of approval is for one year from this date. Each article is approved for 0.5 Elective credits. Credit may be claimed for one year from the date of each article. CME Information: Physicians

10. Statement of Accreditation Statement of Accreditation –Projects In Knowledge, Inc. (PIK) is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center’s Commission on Accreditation. –Projects In Knowledge is also an approved provider by the California Board of Registered Nursing, Provider Number CEP-15227. –This activity is approved for 0.50 nursing contact hours. –There is no fee for this activity. DISCLAIMER: Accreditation refers to educational content only and does not imply ANCC, CBRN, or PIK endorsement of any commercial product or service. CE Information: Nurses

11. Projects In Knowledge ® is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education. This program has been planned and implemented in accordance with the ACPE Criteria for Quality and Interpretive Guidelines. This activity is worth up to 0.5 contact hours (0.05 CEUs). The ACPE Universal Activity Number assigned to this knowledge-type activity is 0052-9999-11-2342-H01-P. Projects In Knowledge ® is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education. This program has been planned and implemented in accordance with the ACPE Criteria for Quality and Interpretive Guidelines. This activity is worth up to 0.5 contact hours (0.05 CEUs). The ACPE Universal Activity Number assigned to this knowledge-type activity is 0052-9999-11-2342-H01-P. CE Information: Pharmacists

12. Calvin J. Cohen, MD, MSc Research Director, CRI New England Clinical Research Director, Harvard Vanguard Medical Associates Boston, Massachusetts Discussant

13. Calvin J. Cohen, MD, MSc has disclosed the following relevant financial relationships: Consulting fees, fees for non-CME services, Contracting research (including PI): Bristol-Myers Squibb, Janssen Pharmaceuticals, Inc., Merck & Co., Inc. Consulting fees: ViiV Healthcare Disclosure Information

14. and have disclosed that they have no relevant financial relationships or conflicts of interest with commercial interests related directly or indirectly to this educational activity. Dori F. Zaleznik, MD, Associate Clinical Professor of Medicine, Harvard Medical School, Boston; Michael Smith; and Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner, have disclosed that they have no relevant financial relationships or conflicts of interest with commercial interests related directly or indirectly to this educational activity. The staffs of Projects In Knowledge and M have no relevant financial relationships or conflicts of interest with commercial interests related directly or indirectly to this educational activity. The staffs of Projects In Knowledge and MedPage Today have no relevant financial relationships or conflicts of interest with commercial interests related directly or indirectly to this educational activity. Disclosure Information

16. Recommended Initial Regimen Two nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) A third agent, from another class: A non-nucleoside reverse transcriptase inhibitor A boosted protease inhibitor An integrase inhibitor

17. Recommended NRTI Backbone Tenofovir/emtricitabine Fixed-dose, single-pill combination. Is also combined with efavirenz in a single-pill combination Once daily Renal dysfunction may influence tenofovir choice

18. Alternative NRTI Backbone Abacavir/lamivudine Available as fixed-dose combination Once daily Weaker efficacy in treatment-naive patients with baseline HIV-1 RNA greater than 100,000 copies/mL than tenofovir/emtricitabine Need to screen for HLA-B*5701b to reduce risk of abacavir hypersensitivity Abacavir may be associated with increased cardiovascular risk

19. Recommended Third Agents Efavirenz Atazanavir/ritonavir Darunavir/ritonavir Raltegravir

20. Efavirenz NNRTI Extensive experience Available in single-pill fixed-dose combination with tenofovir/emtricitabine Low genetic barrier to resistance, so must be taken consistently Choice can be influenced by major psychiatric illness, first trimester of pregnancy, or the intention to become pregnant

21. Atazanavir/ritonavir Boosted PI Once daily Forgiving of missed doses Choice may be influenced by hyperbilirubinemia, the patient’s need for acid-reducing agents, and risk of nephrolithiasis

22. Darunavir/ritonavir Boosted PI Once daily in treatment-naive patients Forgiving of missed doses Experience is limited in treatment-naive patients and there are other options Pill burden higher than atazanavir/ritonavir

23. Raltegravir Only approved integrase inhibitor Twice daily Few toxicities Experience limited in naive patients and there are other options

24. Alternative Key Agents Lopinavir/ritonavir Boosted PI Once daily in naive patients Extensive clinical experience Fosamprenavir/ritonavir Boosted PI Maraviroc CCR5 antagonist/entry inhibitor

25. New Combination: Rilpivirine (NNRTI) with tenofovir/emtricitabine Recently approved, so experience limited Once daily Single pill Lack of teratogenicity may influence regimen choice Pill burden higher than atazanavir/ritonavir

26. The recommended and alternative pairs of NRTIs that form the backbone of a regimen for most treatment-naive patients Potential toxicities and other factors that might influence the choice of NRTI backbone Benefits, such as ease of compliance, that might influence the choice Summary At the end of this activity, participants should understand:

27. The four recommended key third agents and their classes Potential toxicities and other factors that might influence the choice of a key third agent Other key third agents are available as alternatives The elements of the two available single-pill triple-drug combinations Summary