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

Statement of AccreditationStatement 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

Credit DesignationCredit 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

Credit for Family PhysiciansCredit 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. CME Information: Physicians

Statement of AccreditationStatement 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. CE Information: Nurses

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 H04-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 H04-P. CE Information: Pharmacists

Carl W. Dieffenbach, PhD Director Division of AIDS (DAIDS) National Institute of Allergy & Infectious Diseases (NIAID) National Institutes of Health (NIH) Bethesda, Maryland Discussant

Carl W. Dieffenbach, PhD, has disclosed that he has no relevant financial relationships or conflicts of interest to report. Disclosure Information

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 MedPage Today have no relevant financial relationships or conflicts of interest with commercial interests related directly or indirectly to this educational activity. Disclosure Information

SSe Seminal/Vaginal Fluid

Prevent contact with HIV  Barrier methods Reduce/eliminate infectivity from the source  ART as prevention reduces the amount of virus in secretions Reduce target cell susceptibility  Prophylaxis with ART

Transmission Virus Concentration in Extracellular Fluid or Plasma (Copies/ml) Acute HIV-1 Infection Time Post Exposure (days) Virus dissemination Transit eclipse T0T0 CD8 T Cell Responses plasma gp41 Antibody, Day 13 (Non-Neutralizing) Autologous Neutralizing Antibody Escape (new Plasma virus mutants) Autologous gp120 Neutralizing Antibody 11 Weeks CD8 T Cell Responses (new virus mutants) ? Delay T Cell Induced Mutations No Antibody Induced Mutations First Definite Antibody Induced Mutations

Establishment of a Pool of Latently- Infected, Resting CD4+ T Cells During Primary HIV Infection

HIV Replication Cycle binding CD4 fusion coreceptor uncoating core and preintegration complex integration transcription translation assembly budding mRNA TRIM5α reverse transcription APOBEC Vif APOBEC nuclear import

binding CD4 fusion coreceptor uncoating core and preintegration complex integration transcription translation assembly budding mRNA TRIM5α reverse transcription APOBEC Vif APOBEC nuclear import HIV Replication Cycle

A Cure for HIV Infection  The problem: current HIV therapy, while effective, is merely suppressive

HIV targets activated CD4-positive T cells Transmission is made easier by breaks in the genital and anal mucosa HIV forms a reservoir in lymphoid tissue early in the course of infection Summary At the end of this activity, participants should understand:

The course of untreated infection includes a period of latency of months or years during which a patient may have few or no symptoms The HIV replication cycle offers several targets for intervention, including reverse transcription, maturation, entry, and integration Summary