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

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

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.

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

Activity Learning Objective

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

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

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

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

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

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

Recommended Third Agents Efavirenz Atazanavir/ritonavir Darunavir/ritonavir Raltegravir

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

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

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

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

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

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

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:

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