A prospective cohort for ex vivo cure studies with chronic HIV infected patients in the Netherlands: The CHRONO project

A prospective cohort for ex vivo cure studies with chronic HIV infected patients in the Netherlands: The CHRONO project - CHRONO

Status

Recruiting

Phases

Unknown

Study type

Observational

Source

NL-OMON

Registry ID

NL-OMON49028

Enrollment

Registered

2020-09-25

Start date

2021-05-14

Completion date

Unknown

Last updated

2024-04-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

AIDS HIV

Interventions

None listed

Eligibility

Age

18 Years to 99 Years

Inclusion criteria

Inclusion criteria: Adult chronic HIV infected patients of >=18 years of age who initiate antiretroviral therapy in routine care.

Exclusion criteria

Exclusion criteria: A potential subject who meets any of the following criteria will be excluded from participation in this study: 1. Inability to place venous catheters to draw blood. 2. Major comorbidities: a. Severe symptomatic anemia or recent symptomatic cardiovascular event (unstable angina pectoris, decompensated heart failure, myocardial infarction). b. The inability to participate due to any other relevant social, environmental, psychological, factors or according to the HIV treating physician*s judgement.

Design outcomes

Primary

Measure	Time frame
1. The evolution in reservoir size ex vivo as assessed as the number of cells expressing viral RNA and viral protein Gag (vRNA/prGag +/+) in HIV patients on cART at week 24 and 48 after treatment initiation.	—

Secondary

Measure	Time frame
1. The evolution in reservoir size ex vivo as assessed as the number of cells expressing viral RNA and viral protein Gag (vRNA/prGag +/+) in HIV patients on cART at week 24, 48 and 156, and later, after treatment initiation. 2. The evolution of cytotoxic T-lymphocyte responses and inflammatory environment (cell subpopulations, phenotypical cell characterization, pro-inflammatory cytokines), and its relation to the reservoir (endpoint 1.1 and 2.1) and viral load setpoints pre-cART. 3. Assessment of additive, synergistic, or antagonistic effects of (combinations of) established and novel LRA ex vivo as determined by increase in cellular HIV-RNA, protein production and cell decay. 4. Assessment of the underlying mechanisms to explain observed differences in reservoir size and LRA effects, e.g. chromatin accessibility, transcription factor binding, HIV promotor sequencing, or transcriptomics. 5. Differences in the reservoir size and activity, and immune responses (immune activation, cytokines, T/B/NK cell phenotype and functionality) between the HIV subtypes. 6. Evaluation of clinical parameters with reservoir size, activity and host immune responses, including sex, ethnicity, INSTI pharmacokinetics, and HIV clinical characteristics (CD4+T-cell and HIVRNA pre-cART, comedication, HIV center for disease control (CDC) A/B/C events) 7. Correlation between established and future assays of the reservoir*s size and activity.	—

Measure

Time frame

1. The evolution in reservoir size ex vivo as assessed as the number of cells expressing viral RNA and viral protein Gag (vRNA/prGag +/+) in HIV patients on cART at week 24, 48 and 156, and later, after treatment initiation. 2. The evolution of cytotoxic T-lymphocyte responses and inflammatory environment (cell subpopulations, phenotypical cell characterization, pro-inflammatory cytokines), and its relation to the reservoir (endpoint 1.1 and 2.1) and viral load setpoints pre-cART. 3. Assessment of additive, synergistic, or antagonistic effects of (combinations of) established and novel LRA ex vivo as determined by increase in cellular HIV-RNA, protein production and cell decay. 4. Assessment of the underlying mechanisms to explain observed differences in reservoir size and LRA effects, e.g. chromatin accessibility, transcription factor binding, HIV promotor sequencing, or transcriptomics. 5. Differences in the reservoir size and activity, and immune responses (immune activation, cytokines, T/B/NK cell phenotype and functionality) between the HIV subtypes. 6. Evaluation of clinical parameters with reservoir size, activity and host immune responses, including sex, ethnicity, INSTI pharmacokinetics, and HIV clinical characteristics (CD4+T-cell and HIVRNA pre-cART, comedication, HIV center for disease control (CDC) A/B/C events) 7. Correlation between established and future assays of the reservoir*s size and activity.

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Countries

Netherlands

Outcome results