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.
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.
Study Type
OBSERVATIONAL
Enrollment
200
No intervention (observational cohort)
Intact proviral HIV DNA reservoir size in PTC and PIC before and during ATI
Reservoir size will be measured as intact proviral HIV DNA and reported as log copies per 10\^6 CD4+ cells. Reservoir size in PTC, PIC, and NC before and after ATI will be described according to data distribution.
Time frame: 1 year
Total integrated HIV DNA reservoir size in PTC and PIC before and during ATI
Reservoir size will be measured as total integrated HIV DNA and reported as log copies per 10\^6 PBMC. Reservoir size in PTC, PIC, and NC before and after ATI will be described according to data distribution.
Time frame: 1 year
Inducible HIV reservoir size in PTC and PIC before and during ATI
Reservoir size will be measured as inducible HIV and reported as log HIV RNA or HIV DNA copies. Reservoir size in PTC, PIC, and NC before and after ATI will be described according to data distribution.
Time frame: 1 year
Time from the start of ATI until first measurement of HIV RNA >50 copies/mL in PTC and PIC.
A survival analysis will be done for all PTC, PIC and NC who have been sourced from ATI trials. Baseline will be set as the start of the treatment interruption. Time will be noted in weeks until first measurement of HIV-RNA \>50 copies/mL for all study participants. Levels correspond to elite controller definition (Deeks \& Walker, 2007), PTC definition, and level below which HIV onward transmission rarely occurs (Gray et al., 2001). Analysis is by Kaplan Meier and Cox Proportional Hazard models with loss of viral control as event. Independent variables can be timing of ART initiation, duration of ART, HIV cure intervention (if any), demographic parameters (sex, age, place of birth, country of residence), viral dynamics (subtype, reservoir size) and immune characteristics (cd4+ count, cd8+ count, cd4/cd8 ratio).
Time frame: 1 year
Time from the start of ATI until first measurement of HIV RNA >400 copies/mL in PTC and PIC.
A survival analysis will be done for all PTC, PIC and NC who have been sourced from ATI trials. Baseline will be set as the start of the treatment interruption. Time will be noted in weeks until first measurement of HIV-RNA \>400 copies/mL for all study participants. Levels correspond to elite controller definition (Deeks \& Walker, 2007), PTC definition, and level below which HIV onward transmission rarely occurs (Gray et al., 2001). Analysis is by Kaplan Meier and Cox Proportional Hazard models with loss of viral control as event. Independent variables can be timing of ART initiation, duration of ART, HIV cure intervention (if any), demographic parameters (sex, age, place of birth, country of residence), viral dynamics (subtype, reservoir size) and immune characteristics (cd4+ count, cd8+ count, cd4/cd8 ratio).
Time frame: 1 year
Time from the start of ATI until first measurement of HIV RNA > 1000 copies/mL in PTC and PIC.
A survival analysis will be done for all PTC, PIC and NC who have been sourced from ATI trials. Baseline will be set as the start of the treatment interruption. Time will be noted in weeks until first measurement of HIV-RNA \>1000 copies/mL for all study participants. Levels correspond to elite controller definition (Deeks \& Walker, 2007), PTC definition, and level below which HIV onward transmission rarely occurs (Gray et al., 2001). Analysis is by Kaplan Meier and Cox Proportional Hazard models with loss of viral control as event. Independent variables can be timing of ART initiation, duration of ART, HIV cure intervention (if any), demographic parameters (sex, age, place of birth, country of residence), viral dynamics (subtype, reservoir size) and immune characteristics (cd4+ count, cd8+ count, cd4/cd8 ratio).
Time frame: 1 year
Number and severity of adverse events during and after ATI.
Medical events in PTC, PIC and NC recorded in the clinical file will be described using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. If medical events have been reported using varied terminology in the ATI trials, two separate evaluators will reclassify them using CTCAE v5.0 terminology. In instances of conflicting classifications, an impartial researcher will make the final determination.
Time frame: 1 year
Biobank with samples from PTC, PIC and NC including sampling time points and material available.
Available samples will be indexed from previously performed ATI trials. An inventory will be made of the number of samples, type, volume, time of sampling, sampling technique and storage medium.
Time frame: 1 year from screening
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.