HIV/AIDS in Practice. An Expert Commentary with Nelson Michael, MD, PhD. A Clinical Context Report

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1 HIV/AIDS in Practice An Expert Commentary with Nelson Michael, MD, PhD A Clinical Context Report

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

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

4 HIV/AIDS in Practice Clinical Context Series The goal of this series is to provide up-todate 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 Upon successful completion of this educational program, participants should be able to: l Activity Learning Objective Review the relevance and significance of the activity in the broader context of clinical care

7 CME Information: Physicians l 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.

8 l Credit Designation CME Information 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.

9 CME Information: Physicians l 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, 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.

10 l CE Information: Nurses 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 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.

11 Discussant Nelson Michael, MD, PhD Director, U.S. Military HIV Research Program Walter Reed Army Institute of Research Silver Spring, Maryland

12 Disclosure Information Nelson Michael, MD, PhD, has reported he has no real or apparent conflicts of interest to disclose

13 Disclosure Information Robert Jasmer, Associate Clinical Professor of Medicine, University of California, San Francisco; Michael Smith; and Dorothy Caputo, MA, BSN, RN, 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 MedPage Today have no relevant financial relationships or conflicts of interest with commercial interests related directly or indirectly to this educational activity.

14 HIV and CD4-Positive Cells l HIV targets cells expressing the CD4 receptor l To enter the cell, it also requires a chemokine CCR5 or CXCR4 l CCR5 is usually the first chemokine used by wild-type HIV

15 Role of CCR5 l People naturally lacking CCR5 resist HIV infection l One case known where HIV infection apparently cured, after CCR5-negative stem cell transplant. l Researchers now seeking ways to duplicate the effect without a transplant

16 What About CXCR4? l CXCR4 tropism appears to predict worse outcomes l Concern that blocking CCR5 would make matters worse for patients l CCR5 and CXCR4 form heterodimer l Reducing CCR5 leads to reduction in CXCR4

17 RV144 Vaccine Trial l Randomized placebo-controlled trial with 16,402 volunteers in Thailand l 4 priming injections of canarypox vector vaccine plus 2 booster shots of recombinant glycoprotein 120 subunit vaccine l In modified intent-to-treat population, vaccine efficacy was 31.2%

18 Correlates of Infection Risk l Antibodies to second variable loop of env protein associated with protection l Immune pressure seen in viruses that broke through vaccine protection l Efficacy trials planned to see effect of boosting

19 From STEP to HPTN 505 l STEP vaccine used adenovirus 5 and did not include env l Vaccine appeared to increase risk of infection l HPTN 505 enrolling nearly 2,000 MSM in U.S. l Testing env-containing vaccine with different adenovirus vector

20 Summary At the end of this activity, participants should understand: l l l l The role played in HIV infection by the chemokines CCR5 and CXCR4 The therapeutic possibilities offered by modulation of CCR5 The role of antibodies to the env protein in the RV144 vaccine trial The prospects for a more efficacious vaccine building on RV144 results