Ignite Creation Date:
2024-05-06 @ 7:00 PM
Last Modification Date:
2024-10-26 @ 2:58 PM
Study NCT ID:
NCT05852301
Status:
RECRUITING
Last Update Posted:
2023-05-10
First Post:
2023-04-17
Brief Title:
Optimising Cohorts for HIV Cure Interventions
Sponsor:
Bayside Health
Organization:
Bayside Health
Study Overview
Official Title:
Optimising Cohorts for HIV Cure Interventions the Role of Very High CD4 T Cell Counts HI-ART Study
Status:
RECRUITING
Status Verified Date:
2023-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
HI-ART
Brief Summary:
In a recent international substudy of START Study of Initiation of ART in Early HIV Infection we found that people with HIV PHIV who initiate ART with CD4 T cells 800 cellsμL achieve a substantially smaller HIV reservoir on ART as measured by the frequency of CD4 T cells containing HIV DNA compared to individuals who commence ART with CD4 counts between 500-599 and 600-799 cellsµL We have termed these individuals HI-ARTs very High CD4 prior to ART
Smaller reservoirs have also been noted in PHIV who achieve a CD4 count greater than 1000 cellsµL within 48 months of initiation of ART who are referred to as Hypers
This study will establish a prospective cohort of HI-ARTs and Hypers at Alfred Health and our clinical partners It will characterise the HIV reservoir and HIV-specific immune responses in these individuals and compare these to age-matched HIV positive controls from the Alfred HIV clinic who have CD4 T cells between 500-800 cellsuL or who do not reconstitute their CD4 T cells to greater than 1000 cellsuL within 48 months
Participants will be asked to donate a blood sample at baseline and pending initial analyses again at month 12 and 24
Smaller reservoirs have also been noted in PHIV who achieve a CD4 count greater than 1000 cellsµL within 48 months of initiation of ART who are referred to as Hypers
This study will establish a prospective cohort of HI-ARTs and Hypers at Alfred Health and our clinical partners It will characterise the HIV reservoir and HIV-specific immune responses in these individuals and compare these to age-matched HIV positive controls from the Alfred HIV clinic who have CD4 T cells between 500-800 cellsuL or who do not reconstitute their CD4 T cells to greater than 1000 cellsuL within 48 months
Participants will be asked to donate a blood sample at baseline and pending initial analyses again at month 12 and 24
Detailed Description:
In individuals who commence ART in early HIV infection within 6 months of acquiring HIV compared to those who initiate ART in later infection the frequency of cells containing intact and replication competent HIV DNA is reduced and HIV-specific immune responses are better preserved
Previous studies in humans and infected macaque models have demonstrated that smaller reservoirs measured by HIV DNA levels predicted a longer time to viral rebound when ART was interrupted These individuals are difficult to identify and specialist research laboratories are required to conduct HIV DNA assays There is therefore an urgent need to develop simple and efficient processes to identify PHIV with small HIV reservoirs who may best respond to cure interventions aiming to control virus without the need for regular ART
In a recent international substudy of the START study Initiation of ART in Early HIV Infection our group showed that PHIV who initiate ART with CD4 T cells 800 cellsμL achieve a substantially smaller HIV reservoir on ART compared to individuals who commence ART with CD4 counts between 500-800 cellsμL We have termed these individuals Hi-ARTs High CD4 prior to ART Smaller reservoirs have also been noted in PHIV who reach a CD4 count above 1000 cellsμL within 48 months of ART initiation who are referred to as Hypers
The immunological mechanisms by which latently infected cells are more efficiently eliminated or diluted by uninfected CD4 T cells in these patient groups are not understood It is also unclear whether cells containing genetically-intact or replication competent HIV are eliminated at the same rate as cells harbouring HIV with extensive mutationsdeletions defective The distinction between cells harbouring intact or defective HIV is important as only intact virus can cause viral rebound in the absence of ART and there are now assays to distinguish between the two
Blood on enrolment and yearly for 2 years Plasma and peripheral blood mononuclear cells PBMC will be assessed to determine the reservoir size and HIV-specific immune responses using validated assays including total HIV DNA and Intact Proviral DNA IPDA cell associated unspliced HIV-RNA transcriptional activity plasma HIV RNA and intracellular cytokine staining in response to Gag and Nef stimulation using antibodies against IFN-g TNF-a and CD107a Outcome measures will be compared and age- and sex- matched controls from The Alfred Hospital HIV clinic
Previous studies in humans and infected macaque models have demonstrated that smaller reservoirs measured by HIV DNA levels predicted a longer time to viral rebound when ART was interrupted These individuals are difficult to identify and specialist research laboratories are required to conduct HIV DNA assays There is therefore an urgent need to develop simple and efficient processes to identify PHIV with small HIV reservoirs who may best respond to cure interventions aiming to control virus without the need for regular ART
In a recent international substudy of the START study Initiation of ART in Early HIV Infection our group showed that PHIV who initiate ART with CD4 T cells 800 cellsμL achieve a substantially smaller HIV reservoir on ART compared to individuals who commence ART with CD4 counts between 500-800 cellsμL We have termed these individuals Hi-ARTs High CD4 prior to ART Smaller reservoirs have also been noted in PHIV who reach a CD4 count above 1000 cellsμL within 48 months of ART initiation who are referred to as Hypers
The immunological mechanisms by which latently infected cells are more efficiently eliminated or diluted by uninfected CD4 T cells in these patient groups are not understood It is also unclear whether cells containing genetically-intact or replication competent HIV are eliminated at the same rate as cells harbouring HIV with extensive mutationsdeletions defective The distinction between cells harbouring intact or defective HIV is important as only intact virus can cause viral rebound in the absence of ART and there are now assays to distinguish between the two
Blood on enrolment and yearly for 2 years Plasma and peripheral blood mononuclear cells PBMC will be assessed to determine the reservoir size and HIV-specific immune responses using validated assays including total HIV DNA and Intact Proviral DNA IPDA cell associated unspliced HIV-RNA transcriptional activity plasma HIV RNA and intracellular cytokine staining in response to Gag and Nef stimulation using antibodies against IFN-g TNF-a and CD107a Outcome measures will be compared and age- and sex- matched controls from The Alfred Hospital HIV clinic
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None