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UZUCSF ANNUAL RESEARCH DAY 05 MAY 2017 W Samaneka MBChB MSc For ACTG Team Background Current evidence suggests that ART instituted early during acute HIV infection AHI is key to containing HIV reservoir establishment ID: 1032979
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1. A5354/Early ART to Limit Infection and Establishment of Reservoir [EARLIER]UZ-UCSF ANNUAL RESEARCH DAY05 MAY 2017W. SamanekaMBChB, MScFor ACTG Team
2. BackgroundCurrent 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.
3. Natural History of Untreated HIV InfectionAn, Ping et al. Trends in Genetics , Volume 26 , Issue 3 , 119 - 131
4. Clinical Symptoms of AHI Häggström M. Wikiversity Journal of Medicine 1 (2)
5. Usual Course of Treated HIV InfectionStop ARTViral SetpointStart ART
6. Potential Course with InterventionsStop ARTStop ART
7. Stages of Acute HIV Infection(Fiebig Staging)YYPlasma Viral RNA (copies/mL)Days following HIV TransmissionRNAP24 AntigenSpecific EIAPossible presenceof P24 AntigenPresent on Western BlotY 1 2 34Adapted from CUREiculum
8. Establishing the Latent ReservoirResting Memory CD4+ T cellActivated CD4+ T cellHIVCellDeathLatent ReservoirNaïve CD4+ T cellCellSurvivalAdapted from D. Persaud and CUREiculum
9. HIV ReservoirsStevenson. Scientific American 299, 78 - 83 (2008)
10. Why is Early ART Important?One of the most effective ways to contain the HIV reservoir, preserve immunity and reduce immune activationMay optimize responses to immune-based interventions aimed at achieving HIV remissionIs essential to prevent sexual transmission of HIV during acute infectionMay be a critical step in clinical research towards HIV cureAdapted from CUREiculum
11. A5354:Early 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 V
12. 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.
13. ObjectivesTo 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 ARTTo assess how early treatment for HIV affects the numbers of HIV-1 infection fighting cells (CD4+ and CD8+ T-cells) in blood
14. Eligibility Criteria18 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.
15. Important Exclusion CriteriaPositive 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 AHI
16. Study StatusEnrolling (Jan 27, 2017)27/150 enrolledPari CRS target enrolment 15 participants.
17. Site readinessJREC, MRCZ and MCAZ approvalsAwaiting RCZ approvalWebinar training doneTarget activation date May 2017
18. AcknowledgementsNIAIDGilead SciencesUZ-UCSF leadershipProf JG Hakim CABACTG Team
19. THANK YOU