HIV/AIDS in Practice

An Expert Commentary With Carl Dieffenbach, PhD

A Clinical Context Report

Jointly Sponsored by:

and

Clinical Context: HIV/AIDS in PracticeExpert Commentary

This activity is supported by an independent educational grant from

Bristol-Myers Squibb.

Clinical Context: HIV/AIDS in PracticeExpert Commentary

HIV/AIDS in PracticeClinical 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 PracticeClinical 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

Upon successful completion of this educational program, participants should be able to:

Review the relevance and significance of the activity in the broader context of clinical care.

Activity Learning Objective

• Statement of AccreditationThis 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 DesignationProjects 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 PhysiciansMedPage 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

• 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

• 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 0052-9999-11-2108-H04-P.

CE Information: Pharmacists

Carl W. Dieffenbach, PhDDirector

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

SSeSeminal/Vaginal Fluid

Prevent contact with HIV

Prevent contact with HIV Barrier methodsReduce/eliminate infectivity from the sourceART as prevention reduces the amount of virus in secretionsReduce target cell susceptibility Prophylaxis with ART

10-510-4

10-3

10-2

10-10

101

102

103

104105

106

107

108

Transmission

Viru

s Con

cent

ratio

n in

Ext

race

llula

r Fl

uid

or

Plas

ma

(Cop

ies/

ml)

Acute HIV-1 Infection

Time Post Exposure (days)

0 5 10 15 20 30 3525 40 45 50 55 60 65 70

Virus dissemination Transi

t

eclipse

T0

CD8 T CellResponses

plasma gp41 Antibody, Day 13 (Non-Neutralizing)

AutologousNeutralizing

Antibody Escape (new

Plasma virus mutants)

Autologous gp120Neutralizing Antibody

11 Weeks

CD8 T CellResponses

(new virus mutants)

? Delay

T Cell Induced MutationsNo 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 andpreintegrationcomplex

integration

transcription

translation

assembly

budding

mRNA

TRIM5α

reverse transcription

APOBEC

Vif

APOBEC

nuclear import

binding

CD4

fusion

coreceptor

uncoating

core andpreintegrationcomplex

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

SummaryAt 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