Biomarkers for Post-treatment Control in HIV: International Study of the EU2Cure Research Consortium (Phase I)

Официальное название

Biomarkers for Post-treatment Control in HIV: International Multicenter Study of the EU2Cure Research Consortium (EU2Control)

Обзор

Antiretroviral therapy (ART) has transformed HIV from a deadly disease into a lifelong infection that can be controlled. Nevertheless, in the majority of people living with HIV (PWH), discontinuation of ART results in viral rebound due to a latent proviral reservoir. Rarely, individuals known as post-treatment controllers (PTC) demonstrate prolonged viral control even after ceasing ART. Investigating the underlying mechanisms driving this sustained viral control has been a goal for the HIV research community. However, previous studies have been hindered by the scarcity of PTC cases, thereby restricting the potential for associative and translational research. Consequently, the aim of this study is to collect and meta-analyse the data from prior trials where PTC have been identified, as well as to retrospectively identify PTC from the routine care outside trials in a multicentre, multinational study called EU2Control. The aggregated clinical data, and the already collected material from trials where PWH consented for use in additional studies on HIV, will be analyzed with the goal to identify predictive biomarkers for sustained viral control. This study will be part of the research line on HIV cure from an ongoing collaborative consortium (EU2Cure). The first phase of this research line involves a retrospective cohort for meta-analysis and establishment of a biobank.

Подробное описание

Baseline demographic and categorical clinical characteristics of PTC and PIC (sex, ART regimen type, early ART initiation) will be summarized as proportions. Continuous variables (age \[years\], ART duration \[years\], plasma HIV-1 RNA \[copies/mL\], leukocyte counts \[cells/µL\], biochemical parameters) will be summarized separately using descriptive statistics.

Вмешательства

• Другое No Intervention: Observational Cohort
  No intervention (observational cohort)

Первичные конечные точки

• Intact proviral HIV DNA reservoir size in PTC and PIC before and during ATI [Срок оценки: 1 year]
• Total integrated HIV DNA reservoir size in PTC and PIC before and during ATI [Срок оценки: 1 year]
• Inducible HIV reservoir size in PTC and PIC before and during ATI [Срок оценки: 1 year]
• Time from the start of ATI until first measurement of HIV RNA >50 copies/mL in PTC and PIC. [Срок оценки: 1 year]
• Time from the start of ATI until first measurement of HIV RNA >400 copies/mL in PTC and PIC. [Срок оценки: 1 year]
• Time from the start of ATI until first measurement of HIV RNA > 1000 copies/mL in PTC and PIC. [Срок оценки: 1 year]
• Number and severity of adverse events during and after ATI. [Срок оценки: 1 year]
• Biobank with samples from PTC, PIC and NC including sampling time points and material available. [Срок оценки: 1 year from screening]

Критерии участия

Критерии включения

• PTC: Viremic people living with HIV (HIV-RNA >1000c/mL) before ART initiation. Plasma HIV-RNA off ART ≤400c/mL at least 2 times at ≥24weeks apart and at ≥2/3rds of HIV-RNA measurements. Elite PTC with ≤50c/mL will be identified.
• Post intervention controller (PIC): People living with HIV from ATI or MAP studies who meet the PTC criteria as per ATI/MAP study defined. Additional stratification occurs according to the duration of and level of suppressed plasma HIV-RNA (e.g. ≤400c/mL off ART at least 2 times for ≥8 weeks apart). This is done to streamline PIC definitions and capture PIC inMAP studies with an ART pause of less than 24 weeks.
• Controls: non-controllers (NC) with plasma HIV-RNA >1000 c/mL after ART interruption.
• Suppressors: viremic people living with HIV (HIV-RNA >1000c/mL) before ART initiation who became HIV-RNA <50c/mL suppressed on ART, remained on ART, and never had viral rebound.

Критерии исключения

• 1.Documented refusal of data use for research

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07692295 · MEC-2024-0338 · CO-US-985-7598

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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