A5354/Early ART to Limit Infection and Establishment of Res - PowerPoint Presentation

Slide1

A5354/Early ART to Limit Infection and Establishment of Reservoir [EARLIER]

UZ-UCSF ANNUAL RESEARCH DAY05 MAY 2017W. SamanekaMBChB, MScFor ACTG TeamSlide2

Background

Current evidence suggests that ART instituted early during acute HIV infection (AHI) is key to containing HIV reservoir establishment --its critical role in achieving HIV remission

(

Ananworanich

et al 2015)ART initiation at different stages of AHI could predict magnitude and characteristics of HIV-reservoirs, quality and quantity of HIV specific immune responses. This knowledge will inform future immune -based strategies to eliminate latently infected cells.Slide3

Natural History of Untreated HIV Infection

An, Ping et al. Trends in Genetics , Volume 26 , Issue 3 , 119 - 131Slide4

Clinical Symptoms of AHI

Häggström M. Wikiversity Journal of Medicine 1 (2)Slide5

Usual Course of Treated HIV Infection

Stop

ART

Viral

Setpoint

Start

ARTSlide6

Potential Course with Interventions

Stop

ART

Stop

ARTSlide7

Stages of Acute HIV Infection(

Fiebig Staging)

Y

Y

Plasma Viral RNA (copies/mL)

Days following HIV Transmission

RNA

P24 Antigen

Specific EIA

Possible presence

of P24 Antigen

Present on

Western Blot

Y

1

2

3

4

Adapted from

CUREiculumSlide8

Establishing the Latent Reservoir

Resting Memory

CD4+ T cell

Activated CD4+ T cell

HIV

Cell

Death

Latent Reservoir

Naïve CD4+ T cell

Cell

Survival

Adapted from D.

Persaud

and

CUREiculumSlide9

HIV Reservoirs

Stevenson. Scientific American 299, 78 - 83 (2008)Slide10

Why is Early ART Important?

One of the most effective ways to contain the HIV reservoir, preserve immunity and reduce immune activation

May optimize responses to immune-based interventions aimed at achieving HIV remission

Is essential to prevent sexual transmission of HIV during acute infection

May be a critical step in clinical research towards HIV cure

Adapted from

CUREiculumSlide11

A5354:E

arly ART to Limit Infection and Establishment of Reservoir (EARLIER)

Will enroll 150 participants identified during acute HIV infection at ACTG sites.

Fiebig

stage-classification to characterize the progression from HIV-1 exposure to seroconversion at time of ART initiation.50 Fiebig I/II50 Fiebig III/IV50 Fiebig

VSlide12

A5354/EARLIER

Participants will be offered immediate ART (within 48hr)Single tablet regimen (EVG/COB/FTC/TAF)Will evaluate reservoir size after 1 year of ART across a variety of body compartments.Slide13

Objectives

To assess how starting ART as soon as the infection is found affects the amount of HIV-1 in blood and how well the body fights the HIV-1 infection.To measure the amount of HIV-1 DNA (genetic material for HIV-1) seen in CD4+ T-cells (infection-fighting cells in blood) after 48 weeks of ART

To assess

how early treatment for HIV affects the numbers of HIV-1 infection fighting cells (CD4+ and CD8+ T-cells) in bloodSlide14

Eligibility Criteria

18 years and aboveAppropriate documentation from medical records of diagnosis of acute HIV-1 infection (AHI) within 7 days prior to enrollment.[Referrals from prevention trials]Ability and willingness to initiate ART at enrollment.Slide15

Important Exclusion Criteria

Positive HIV-1 antibody test ≥90 days prior to study entry.(outreach.. CAB)AHI diagnosis within 60 days after receiving any investigational ARV or HIV-1 vaccine or immune prophylaxis for HIV-1 infectionInitiation of ARVs for PREP and PEP within 60 days prior to diagnosis of AHISlide16

Study Status

Enrolling (Jan 27, 2017)27/150 enrolledPari CRS target enrolment 15 participants.Slide17

Site readiness

JREC, MRCZ and MCAZ approvalsAwaiting RCZ approvalWebinar training doneTarget activation date May 2017Slide18

Acknowledgements

NIAIDGilead SciencesUZ-UCSF leadershipProf JG Hakim CABACTG TeamSlide19

THANK YOU