Download and Clinical Context: HIV/AIDS in Practice Expert

HIV/AIDS in Practice
An Expert Commentary With
Carl Dieffenbach, PhD
A Clinical Context Report
Clinical Context: HIV/AIDS in Practice
Expert Commentary
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.
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.
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
CME Information: Physicians
• 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
• 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: 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.
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-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: Pharmacists
• 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.
Discussant
Carl W. Dieffenbach, PhD
Director
Division of AIDS (DAIDS)
National Institute of Allergy & Infectious
Diseases (NIAID)
National Institutes of Health (NIH)
Bethesda, Maryland
Disclosure Information
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.
Seminal/Vaginal FluidSSe
Prevent contact with HIV
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
Acute HIV-1 Infection
Virus Concentration in Extracellular Fluid
or
Plasma (Copies/ml)
plasma gp41 Antibody, Day 13 (Non-Neutralizing)
108
Autologous gp120
Neutralizing Antibody
11 Weeks
? Delay
107
106
105
104
eclipse
103
102
CD8 T Cell
Responses
101
0
10-1
10-2
Transit
10-3
T0
Autologous
Neutralizing
Antibody
Escape (new
Plasma virus mutants)
Virus
(new virus mutants)
dissemination
10-4
10-5
0
Transmission
5
10
15
20
25
30
35
40
45
50
55
60
65
70
Time Post Exposure (days)
T Cell Induced Mutations
No Antibody Induced Mutations
First Definite Antibody
Induced Mutations
Establishment of a
Pool of LatentlyInfected, Resting
CD4+ T Cells During
Primary HIV
Infection
HIV Replication Cycle
fusion
binding
core and
preintegration
complex
reverse transcription
APOBEC
uncoating
TRIM5α
nuclear import
transcription
mRNA
translation
integration
assembly
coreceptor
CD4
APOBEC
Vif
budding
HIV Replication Cycle
fusion
binding
core and
preintegration
complex
reverse transcription
APOBEC
uncoating
TRIM5α
nuclear import
transcription
mRNA
translation
integration
assembly
coreceptor
CD4
APOBEC
Vif
budding
A Cure for HIV Infection
 The problem: current HIV therapy, while effective, is
merely suppressive
Summary
At the end of this activity, participants should understand:
• 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
• 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