HIV-1-infectionHI-ARTNCT05852301
Optimising Cohorts for HIV Cure Interventions
An observational study of HIV-1-infection, run by Bayside Health at 1 site in Australia.
Trial 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 cells/μL achieve a substantially smaller HIV reservoir on ART, as measured by the frequency of CD4+ T cells containing HIV DNA, compared to… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- HIV-1-infection
- How many people
- 112 participants
- Where
- 1 siteAustralia
- Study dates
- 16 Mar 2023to 31 Dec 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Individuals who are HIV antibody positive; have very high CD4 counts on ART initiation (>800 cells/uL , known as HI-ARTs), or reconstitute their CD4 counts to >1000 cells/μL within 48 months of commencing ART (Hypers) will be eligible for inclusion. The study will recruit people with HIV into 4 cohorts based on CD4+ T cell criteria. * CD4+ T cells > 800 c/uL on ART initiation (HI-ARTs) * CD4+ T cells between 350-800 c/uL on ART initiation (HI-ART controls) * CD4+ T cells <800 c/μL on ART initiation, but increase to >1000c/μL within 48 months of ART initiation (Hypers) * CD4+ T cells reconstituted to 500-1000c/μL within 48 months (Hyper controls) The study consists of three study visits over 24 months with study visits and blood sampling at months 0, 12 and 24.
Who may be able to join
- Aged 18 years or older
- Able to give written informed consent;
- Documented HIV infection (antibody positive);
- Taking continuous ART for at least 2 years prior to study enrolment;
Who cannot join
- Unwillingness to follow protocol requirements;
- HIV negative;
- Not meeting study definition for HI-ART or Hyper (except for control group);
- Medicare ineligible
Trial locations and contacts
1 site in 1 country.
Australia1 site, 1 recruiting
- Recruiting
Alfred Health
Prahran, Victoria, 3181
Jillian Lau
About this study
Official title: Optimising Cohorts for HIV Cure Interventions: the Role of Very High CD4 T Cell Counts: HI-ART Study
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 cells/μL 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 cells/µL. 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 cells/µL within 48 months of initiation of ART who are referred to as 'Hypers'.
Read more
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 cells/uL, or who do not reconstitute their CD4+ T cells to greater than 1000 cells/uL within 48 months.
Participants will be asked to donate a blood sample at baseline, and pending initial analyses, again at month 12 and 24.
Read the 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 cells/μL achieve a substantially smaller HIV reservoir on ART compared to individuals who commence ART with CD4 counts between 500-800 cells/μL. 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 cells/μL 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 mutations/deletions ('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.
- Conditions
- HIV-1-infection
- Being tested
- no intervention
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
no interventionOther
no intervention, observational study only
| Study group | Role | What they receive |
|---|---|---|
| HI-ART | People living with HIV with CD4+ T cells > 800 c/uL on ART initiation Receives: Other: no intervention | |
| HI-ART control | People living with HIV with CD4+ T cells between 500-800 c/uL on ART initiation Receives: Other: no intervention | |
| Hyper | People living with HIV with CD4+ T cells >800 c/μL on ART initiation, but increase to >1000c/μL within 48 months of ART initiation Receives: Other: no intervention | |
| Hyper control | People living with HIV with CD4+ T cells <500 c/μL on ART initiation and reconstituted to 500-1000c/μL within 48 months of ART initiation Receives: Other: no intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
HIV-DNA
Quantitative DNA measurements in CD4+ T cells by PCR
Measured: at baseline
Secondary outcomes (6)
Reservoir measurements
Quantitative HIV RNA/DNA measurements in CD4+ T cells by PCR
Measured: at baseline
Reservoir measurements
flow cytometry
Measured: at baseline
Reservoir measurements
proviral sequencing
Measured: at baseline
HIV-specific T-cell responses
HIV-specific T-cell immunity by intracellular cytokine staining (ICS) to measure the frequency of responding cells producing multiple effector cytokines including IFN-γ, TNF-α, and IL-2.
Measured: at baseline
Decay of reservoir
Compare changes in intact/defective HIV DNA by PCR from baseline
Measured: at 12 months
Decay of reservoir
Compare changes in intact/defective HIV DNA by PCR from baseline
Measured: at 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 May 2023
- Study start16 Mar 2023
- Primary completion30 Jun 2025 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIV-1-infectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 112 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Bayside Health
- Sponsor type
- Other government
- Collaborators
- The Peter Doherty Institute for Infection and Immunity
- Responsible party
- Sponsor
- Investigators
- Jillian Lau, MBBS, Principal investigator, The Alfred
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05852301
- Sponsor's protocol ID
- 413.22
- Acronym
- HI-ART
- Status last verified
- Apr 2023
- First submitted
- 17 Apr 2023
- Last updated
- 10 May 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 10 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Optimising Cohorts for HIV Cure Interventions: the Role of Very High CD4 T Cell Counts: HI-ART Study
- ClinicalTrials.gov ID
- NCT05852301
- Acronym / sponsor ID
- HI-ART / 413.22
- Conditions
- HIV-1-infection
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 112 participants (estimated)
- Lead sponsor
- Bayside HealthOther government
- Collaborators
- The Peter Doherty Institute for Infection and Immunity
- Study start
- 16 Mar 2023 (actual)
- Primary completion
- 30 Jun 2025 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 10 May 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 cells/μL 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 cells/µL. 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 cells/µL 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 cells/uL, or who do not reconstitute their CD4+ T cells to greater than 1000 cells/uL 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 cells/μL achieve a substantially smaller HIV reservoir on ART compared to individuals who commence ART with CD4 counts between 500-800 cells/μL. 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 cells/μL 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 mutations/deletions ('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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| HI-ART | – | Other: no interventionPeople living with HIV with CD4+ T cells > 800 c/uL on ART initiation |
| HI-ART control | – | Other: no interventionPeople living with HIV with CD4+ T cells between 500-800 c/uL on ART initiation |
| Hyper | – | Other: no interventionPeople living with HIV with CD4+ T cells >800 c/μL on ART initiation, but increase to >1000c/μL within 48 months of ART initiation |
| Hyper control | – | Other: no interventionPeople living with HIV with CD4+ T cells <500 c/μL on ART initiation and reconstituted to 500-1000c/μL within 48 months of ART initiation |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Individuals who are HIV antibody positive; have very high CD4 counts on ART initiation (>800 cells/uL , known as HI-ARTs), or reconstitute their CD4 counts to >1000 cells/μL within 48 months of commencing ART (Hypers) will be eligible for inclusion. The study will recruit people with HIV into 4 cohorts based on CD4+ T cell criteria. * CD4+ T cells > 800 c/uL on ART initiation (HI-ARTs) * CD4+ T cells between 350-800 c/uL on ART initiation (HI-ART controls) * CD4+ T cells <800 c/μL on ART initiation, but increase to >1000c/μL within 48 months of ART initiation (Hypers) * CD4+ T cells reconstituted to 500-1000c/μL within 48 months (Hyper controls) The study consists of three study visits over 24 months with study visits and blood sampling at months 0, 12 and 24.
Key inclusion criteria (4 listed)
- Aged 18 years or older
- Able to give written informed consent;
- Documented HIV infection (antibody positive);
- Taking continuous ART for at least 2 years prior to study enrolment;
Key exclusion criteria (4 listed)
- Unwillingness to follow protocol requirements;
- HIV negative;
- Not meeting study definition for HI-ART or Hyper (except for control group);
- Medicare ineligible
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| no interventionno intervention, observational study only | Other | HI-ART, HI-ART control, Hyper, Hyper control |
Primary outcome
HIV-DNA
Time frame: at baseline
Quantitative DNA measurements in CD4+ T cells by PCR
6 secondary outcomes
Reservoir measurements
Time frame: at baseline
Reservoir measurements
Time frame: at baseline
Reservoir measurements
Time frame: at baseline
HIV-specific T-cell responses
Time frame: at baseline
Decay of reservoir
Time frame: at 12 months
Decay of reservoir
Time frame: at 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2023.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jillian Lau, MBBS principal investigator
The Alfred
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of HIV-1-infection, run by Bayside Health at 1 site in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 10 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jillian Lau, MBBS (613 90766908, Jillian.Lau@monash.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
HIV-DNA (time frame: at baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 May 2023.