Trial Outcomes & Findings for LoViReT (Low Viral Reservoir Treated Patients) (NCT NCT02972931)
NCT ID: NCT02972931
Last Updated: 2024-09-19
Results Overview
To address this objective, a longitudinal analysis of proviral HIV DNA for each patient will be performed, including time points previous to cART. In total, 200 samples will be analyzed and dynamic models will be built for the two different levels of reservoir establishment. General immune phenotype of cellular populations, including also activation markers, will be also assessed in all time points.
Recruitment status
COMPLETED
Target enrollment
62 participants
Primary outcome timeframe
The time frame for the outcome measure is an average of 5 years. Including a baseline, 18 months, and 5 years post cART initiation.
Results posted on
2024-09-19
Participant Flow
Reanalysis of total HIV DNA in 30 LoViReT and 32 control patients of the cohort was made, and 22 LoViReT patients and 22 controls were finally selected for the study (the ones still fulfilling criteria). In terms of apheresis and tissue samples of the LoViReT patients, we finally collected: 14 apheresis, 8 lymph node FNB and 8 rectal biopsies.
Participant milestones
| Measure |
LoViReT
HIV-infected subjects with extremely low or undetectable HIV-1 DNA levels in peripheral blood despite having initiated cART during chronic HIV-1 infection
|
Standard Reservoir Level
HIV-infected subjects who initiated cART during chronic HIV-1 infection and that show standard HIV-1 DNA levels in peripheral blood
|
|---|---|---|
|
Overall Study
STARTED
|
30
|
32
|
|
Overall Study
COMPLETED
|
22
|
22
|
|
Overall Study
NOT COMPLETED
|
8
|
10
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
LoViReT (Low Viral Reservoir Treated Patients)
Baseline characteristics by cohort
| Measure |
LoViReT
n=22 Participants
HIV-infected subjects with extremely low or undetectable HIV-1 DNA levels in peripheral blood despite having initiated cART during chronic HIV-1 infection
|
Standard Reservoir Level
n=22 Participants
HIV-infected subjects who initiated cART during chronic HIV-1 infection and that show standard HIV-1 DNA levels in peripheral blood
|
Total
n=44 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
50.70 years
n=99 Participants
|
51.01 years
n=107 Participants
|
50.70 years
n=206 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
7 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
17 Participants
n=99 Participants
|
20 Participants
n=107 Participants
|
37 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Race · Caucasian
|
20 Participants
n=99 Participants
|
17 Participants
n=107 Participants
|
37 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Race · Non caucasian
|
0 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
5 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Race · Not available
|
2 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
|
Region of Enrollment
Spain
|
22 Participants
n=99 Participants
|
22 Participants
n=107 Participants
|
44 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: The time frame for the outcome measure is an average of 5 years. Including a baseline, 18 months, and 5 years post cART initiation.Population: The participants analyzed correspond to a subgroup of participants with sample availability for all the timepoints analyzed, and started cART during chronic HIV-1 infection.
To address this objective, a longitudinal analysis of proviral HIV DNA for each patient will be performed, including time points previous to cART. In total, 200 samples will be analyzed and dynamic models will be built for the two different levels of reservoir establishment. General immune phenotype of cellular populations, including also activation markers, will be also assessed in all time points.
Outcome measures
| Measure |
LoViReT
n=12 Participants
HIV-infected subjects with extremely low or undetectable HIV-1 DNA levels in peripheral blood despite having initiated cART during chronic HIV-1 infection
|
Standard Reservoir Level
n=13 Participants
HIV-infected subjects who initiated cART during chronic HIV-1 infection and that show standard HIV-1 DNA levels in peripheral blood
|
|---|---|---|
|
Longitudinal Analysis of Total HIV DNA and Immune-phenotype by Digital Droplet Polymerase Chain Reaction (PCR) and Flow Cytometry, Respectively, Comparing This Outcome Before and After cART (Evaluation of cART Effect on This Parameters)
Baseline
|
812 DNA copies/milion of CD4 T cells
Interval 485.0 to 1392.0
|
5062 DNA copies/milion of CD4 T cells
Interval 2649.0 to 8943.0
|
|
Longitudinal Analysis of Total HIV DNA and Immune-phenotype by Digital Droplet Polymerase Chain Reaction (PCR) and Flow Cytometry, Respectively, Comparing This Outcome Before and After cART (Evaluation of cART Effect on This Parameters)
Last sample
|
54 DNA copies/milion of CD4 T cells
Interval 38.0 to 67.0
|
714 DNA copies/milion of CD4 T cells
Interval 517.0 to 1462.0
|
PRIMARY outcome
Timeframe: The time frame for the outcome measure is on patients on cART for at least 5 years.Population: The participants analyzed correspond to a subgroup LoVireT who agreed to have a phlebotomy. No results for control group because de phlebotomy was not indicated.
Replication competent reservoir will be analyzed with the gold standard quantitative viral outgrowth assay (qVOA).
Outcome measures
| Measure |
LoViReT
n=14 Participants
HIV-infected subjects with extremely low or undetectable HIV-1 DNA levels in peripheral blood despite having initiated cART during chronic HIV-1 infection
|
Standard Reservoir Level
HIV-infected subjects who initiated cART during chronic HIV-1 infection and that show standard HIV-1 DNA levels in peripheral blood
|
|---|---|---|
|
Replication Competent Reservoir in Patients With Low (LoViReT) Normal (Controls) Levels of Total HIV DNA
Positive
|
4 Participants
|
—
|
|
Replication Competent Reservoir in Patients With Low (LoViReT) Normal (Controls) Levels of Total HIV DNA
Negative
|
10 Participants
|
—
|
PRIMARY outcome
Timeframe: The time frame for the outcome measure is on samples before initiation of cART and after 5 years on cARTPopulation: 11 LoViReT and 11 controls with available samples before initiation of cART and after 5 years on cART were analyzed
Functional T-cell response will be measured isolating CD8 T and Nk cells and measuring the inhibition capacity for HIV replication in each patient.
Outcome measures
| Measure |
LoViReT
n=11 Participants
HIV-infected subjects with extremely low or undetectable HIV-1 DNA levels in peripheral blood despite having initiated cART during chronic HIV-1 infection
|
Standard Reservoir Level
n=11 Participants
HIV-infected subjects who initiated cART during chronic HIV-1 infection and that show standard HIV-1 DNA levels in peripheral blood
|
|---|---|---|
|
Evaluation and Comparison of CD8 T-cell Responses by Inhibition Assays, Between Patients With Low (LoViReT) and Normal (Controls) Levels of Total HIV DNA
CD8 T cells pre cART
|
27.05 percentage of inhibition
Interval 0.0 to 39.37
|
57.33 percentage of inhibition
Interval 52.77 to 81.36
|
|
Evaluation and Comparison of CD8 T-cell Responses by Inhibition Assays, Between Patients With Low (LoViReT) and Normal (Controls) Levels of Total HIV DNA
CD8 T cells 5 years on cART
|
28.09 percentage of inhibition
Interval 0.0 to 57.05
|
41.21 percentage of inhibition
Interval 0.0 to 76.25
|
|
Evaluation and Comparison of CD8 T-cell Responses by Inhibition Assays, Between Patients With Low (LoViReT) and Normal (Controls) Levels of Total HIV DNA
NK cells pre cART
|
57.52 percentage of inhibition
Interval 14.54 to 77.36
|
50.17 percentage of inhibition
Interval 10.56 to 69.53
|
|
Evaluation and Comparison of CD8 T-cell Responses by Inhibition Assays, Between Patients With Low (LoViReT) and Normal (Controls) Levels of Total HIV DNA
NK cells 5 years on cART
|
38.61 percentage of inhibition
Interval 5.71 to 54.2
|
42.77 percentage of inhibition
Interval 0.88 to 63.51
|
PRIMARY outcome
Timeframe: The time frame for the outcome measure is on patients on cART for at least 5 years.Different progression-associated genetic factors, such as HLA type, and CCR5, CCR2 and SIGLEC-1 single nucleotide polymorphisms (SNPs) will be also explored.
Outcome measures
| Measure |
LoViReT
n=22 Participants
HIV-infected subjects with extremely low or undetectable HIV-1 DNA levels in peripheral blood despite having initiated cART during chronic HIV-1 infection
|
Standard Reservoir Level
n=22 Participants
HIV-infected subjects who initiated cART during chronic HIV-1 infection and that show standard HIV-1 DNA levels in peripheral blood
|
|---|---|---|
|
Analysis and Comparison of Progression-associated Genetic Factors, Between Patients With Low (LoViReT) and Normal (Controls) Levels of Total HIV DNA
Siglec-1 genotype · heterozygous
|
1 Participants
|
1 Participants
|
|
Analysis and Comparison of Progression-associated Genetic Factors, Between Patients With Low (LoViReT) and Normal (Controls) Levels of Total HIV DNA
Siglec-1 genotype · mutated homozygous
|
0 Participants
|
0 Participants
|
|
Analysis and Comparison of Progression-associated Genetic Factors, Between Patients With Low (LoViReT) and Normal (Controls) Levels of Total HIV DNA
Siglec-1 genotype · Not available
|
0 Participants
|
0 Participants
|
|
Analysis and Comparison of Progression-associated Genetic Factors, Between Patients With Low (LoViReT) and Normal (Controls) Levels of Total HIV DNA
CCR5 genotype · wild type homozygous
|
16 Participants
|
11 Participants
|
|
Analysis and Comparison of Progression-associated Genetic Factors, Between Patients With Low (LoViReT) and Normal (Controls) Levels of Total HIV DNA
CCR5 genotype · heterozygous
|
6 Participants
|
3 Participants
|
|
Analysis and Comparison of Progression-associated Genetic Factors, Between Patients With Low (LoViReT) and Normal (Controls) Levels of Total HIV DNA
CCR5 genotype · mutated homozygous
|
0 Participants
|
0 Participants
|
|
Analysis and Comparison of Progression-associated Genetic Factors, Between Patients With Low (LoViReT) and Normal (Controls) Levels of Total HIV DNA
CCR5 genotype · Not available
|
0 Participants
|
8 Participants
|
|
Analysis and Comparison of Progression-associated Genetic Factors, Between Patients With Low (LoViReT) and Normal (Controls) Levels of Total HIV DNA
Siglec-1 genotype · wild type homozygous
|
21 Participants
|
21 Participants
|
PRIMARY outcome
Timeframe: The time frame for the outcome measure is on patients on cART for at least 5 years.Population: Loviret and controls were analyzed for virus tropism
Genotypic HIV tropism and the full viral genome will be analyzed through sequencing from DNA of patients' peripheral blood mononuclear cells (PBMC).
Outcome measures
| Measure |
LoViReT
n=22 Participants
HIV-infected subjects with extremely low or undetectable HIV-1 DNA levels in peripheral blood despite having initiated cART during chronic HIV-1 infection
|
Standard Reservoir Level
n=22 Participants
HIV-infected subjects who initiated cART during chronic HIV-1 infection and that show standard HIV-1 DNA levels in peripheral blood
|
|---|---|---|
|
Measurement of Genotypic Tropism in Patients With Low (LoViReT) and Normal (Controls) Levels of Total HIV DNA
CCR5
|
12 Participants
|
18 Participants
|
|
Measurement of Genotypic Tropism in Patients With Low (LoViReT) and Normal (Controls) Levels of Total HIV DNA
CXCR4
|
1 Participants
|
3 Participants
|
|
Measurement of Genotypic Tropism in Patients With Low (LoViReT) and Normal (Controls) Levels of Total HIV DNA
Not determined
|
9 Participants
|
1 Participants
|
Adverse Events
LoViReT
Serious events: 1 serious events
Other events: 4 other events
Deaths: 0 deaths
Standard Reservoir Level
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
LoViReT
n=22 participants at risk
HIV-infected subjects with extremely low or undetectable HIV-1 DNA levels in peripheral blood despite having initiated cART during chronic HIV-1 infection
|
Standard Reservoir Level
n=22 participants at risk
HIV-infected subjects who initiated cART during chronic HIV-1 infection and that show standard HIV-1 DNA levels in peripheral blood
|
|---|---|---|
|
Nervous system disorders
Saddle dermatoma
|
4.5%
1/22 • Number of events 1 • 1 year
The clinical investigators were responsible for detecting and documenting any event that meets the criteria and definitions of adverse event (AE) or serious adverse event (SAE) for this protocol. Adverse events occurred during the visit were recorded in the database and included in the final report.
|
0.00%
0/22 • 1 year
The clinical investigators were responsible for detecting and documenting any event that meets the criteria and definitions of adverse event (AE) or serious adverse event (SAE) for this protocol. Adverse events occurred during the visit were recorded in the database and included in the final report.
|
Other adverse events
| Measure |
LoViReT
n=22 participants at risk
HIV-infected subjects with extremely low or undetectable HIV-1 DNA levels in peripheral blood despite having initiated cART during chronic HIV-1 infection
|
Standard Reservoir Level
n=22 participants at risk
HIV-infected subjects who initiated cART during chronic HIV-1 infection and that show standard HIV-1 DNA levels in peripheral blood
|
|---|---|---|
|
General disorders
Swelling
|
9.1%
2/22 • Number of events 2 • 1 year
The clinical investigators were responsible for detecting and documenting any event that meets the criteria and definitions of adverse event (AE) or serious adverse event (SAE) for this protocol. Adverse events occurred during the visit were recorded in the database and included in the final report.
|
0.00%
0/22 • 1 year
The clinical investigators were responsible for detecting and documenting any event that meets the criteria and definitions of adverse event (AE) or serious adverse event (SAE) for this protocol. Adverse events occurred during the visit were recorded in the database and included in the final report.
|
|
Infections and infestations
Acute bronchitis
|
9.1%
2/22 • Number of events 2 • 1 year
The clinical investigators were responsible for detecting and documenting any event that meets the criteria and definitions of adverse event (AE) or serious adverse event (SAE) for this protocol. Adverse events occurred during the visit were recorded in the database and included in the final report.
|
0.00%
0/22 • 1 year
The clinical investigators were responsible for detecting and documenting any event that meets the criteria and definitions of adverse event (AE) or serious adverse event (SAE) for this protocol. Adverse events occurred during the visit were recorded in the database and included in the final report.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60