AIDS, AIDS Vaccines
Conditions
Keywords
CMI, Antiretroviral therapy-naïve, HIV
Brief summary
The purpose of this study is to investigate a combined set of parameters deemed to impact the quality of CMI analyses in terms of the proportion of viable lymphocytes in antiretroviral therapy-naïve HIV-1 infected subjects.
Detailed description
This study will address the respective and combined impact of (i) timing between blood collection and peripheral blood mononuclear cells (PBMC) processing \[time-to-process\] and (ii) timing of PBMC resting before stimulation \[resting -time\].
Interventions
PROCEDUREBlood sample collection
Blood samples will be collected in all subjects at two time points, at the Screening Visit (Day 0) and at the Sample Collection Visit (Day 15)
Sponsors
GlaxoSmithKline
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
All subjects must satisfy all the following criteria at study entry: * Subjects who the Investigator believes can and will comply with the requirements of the protocol. * Written informed consent obtained from the subject prior to any study procedure. * A male or female between and including 18 and 55 years of age at the time of enrollment. * Confirmed HIV-1 infection. * ART-naïve and not eligible for ART treatment as per established guidelines. Subjects must never have received ART after HIV diagnosis, including lamivudine used for chronic hepatitis B infection. The exception to this is short-term ART for prevention of mother-to-child transmission (PMTCT) which must have been completed at least 360 days prior to enrollment. * Viral load level between and including 2,000 and 100,000 copies/mL at screening. * CD4+ T cell count \>500 cells/mm3 at screening. * If the subject is female, she must be of non-childbearing potential, i.e., have a current tubal ligation, hysterectomy, ovariectomy or be post-menopausal. Female subjects of childbearing potential may be enrolled in the study, if the subject: * has practiced adequate contraception for 30 days prior to vaccination, and * has a negative pregnancy test at screening, and * has agreed to continue adequate contraception during the entire study period.
Exclusion criteria
The following criteria should be checked at the time of study entry. If any exclusion criterion applies, the subject must not be included in the study: * Infection with HIV-2. This includes subjects with dual infection with HIV-1/HIV-2. * Planned use of any hematotoxic product during the study period. * Planned use of any investigational or non-registered product during the study period. * Acute or chronic, clinically relevant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination, serology and/or medical history at screening. * Grade 3 or grade 4 laboratory abnormalities, as defined by Division of AIDS (DAIDS) grading table, at screening. * Any condition which, in the opinion of the Investigator, could compromise the subject's adherence to the study protocol. * Planned administration of a vaccine not foreseen by the study protocol during the period starting 30 days before the Sample Collection Visit (Visit 2). Vaccine can be administered as after sampling in Visit 2. * Pregnant or lactating female.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Lymphocytes Viability Prediction (Non-transformed Estimate) in CMI Samples Post-overnight Incubation Time Before ICS: Optimum Mean Cell Viability Estimates by the Prediction Model -Condition None Resting Time Included. | At Day 15 (sample collection visit) | The objective was to model lymphocyte viability according to time-to-process (TP=2h, 7h or 24h) and resting time (RT=0h) conditions in order to select the best combination of these two parameters with the aim to maximize the post-ICS viability in CMI samples collected from ART-naïve HIV-1-infected subjects. Viability (%) = 10 \^ P / (1 + 10 \^ P) \* 100 with P for Prediction. The optimum of the viability was predicted as follows. P (LOGIT)= intercept + a\*TP + b\*RT + a\*b\*TP\*RT + + b\*b\*RT\*RT. Where intercept, TP, RT, TP\*RT, TP \*TP, RT\*RT are the parameters evaluated and presented in the primary outcomes 5, 6 and 7. And a and b are parameters (hour) corresponding respectively to the TP and the RT where the prediction has to be done. The optimum predicted mean cell viability of this Design of Experiment is presented in this outcome and expressed as percentage. |
| Lymphocytes Viability Prediction (LOGIT Transformed Estimate) in CMI Samples Post-overnight Incubation Time Before ICS: Optimum Mean Cell Viability Estimate by the Prediction Model - Condition None Resting Time Not Included | At Day 15 (sample collection visit) | The objective was to model lymphocyte viability according to time-to-process (TP=2h, 7h or 24h) and resting time (RT=2h, 6h or 18h \[none resting time not included\]) conditions to select the best combination of these two parameters to maximize the post-ICS viability in CMI samples collected from ART-naïve HIV-1-infected subjects. Viability (%) = 10 \^ P / (1 + 10 \^ P) \* 100 with P for Prediction.The optimum of the viability was predicted as P (LOGIT)= intercept + a\*TP + b\*RT + a\*b\*TP\*RT + a\*a\*TP\*TP + b\*b\*RT\*RT. Where intercept, TP, RT, TP\*RT, TP \*TP, RT\*RT are the parameters evaluated and presented in the 3 first primary outcomes. And a and b are log-transformed parameters corresponding respectively to the TP and the RT where the prediction has to be done. The optimum predicted mean cell viability of this Design of Experiment is presented in this outcome and expressed as percentage. |
| Lymphocytes Viability Prediction (Non-transformed Estimate) in CMI Samples Post-overnight Incubation Time Before ICS: Intercept Parameter Estimate of the Prediction Model - Condition None Resting Time Included | At Day 15 (sample collection visit) | The objective was to model lymphocyte viability according to time-to-process (TP=2h, 7h or 24h) and resting time (RT=0h) conditions in order to select the best combination of these two parameters with the aim to maximize the post-ICS viability in CMI samples collected from ART-naïve HIV-1-infected subjects. Viability (%) = 10 \^ P / (1 + 10 \^ P) \* 100 with P for Prediction. The optimum of the viability was predicted as follows. P (LOGIT)= intercept + a\*TP + b\*RT + a\*b\*TP\*RT + + b\*b\*RT\*RT. Where intercept, TP, RT, TP\*RT, TP \*TP, RT\*RT are the parameters evaluated and presented in the primary outcomes 5, 6 and 7. And a and b are parameters (hour) corresponding respectively to the TP and the RT where the prediction has to be done. This outcome is presenting the intercept i.e. expected mean value of Prediction when TP and RT = 0. The optimum of this Design of Experiment is presented in outcome 8. |
| Lymphocytes Viability Prediction (Non-transformed Estimate) in CMI Samples Post-overnight Incubation Time Before ICS: Time to Process and Resting Time Parameter Estimates of the Prediction Model - Condition None Resting Time Included | At Day 15 (sample collection visit) | The objective was to model lymphocyte viability according to time-to-process (TP=2h, 7h or 24h) and resting time (RT=0h) conditions in order to select the best combination of these two parameters with the aim to maximize the post-ICS viability in CMI samples collected from ART-naïve HIV-1-infected subjects. Viability (%) = 10 \^ P / (1 + 10 \^ P) \* 100 with P for Prediction. The optimum of the viability was predicted as follows. P (LOGIT)= intercept + a\*TP + b\*RT + a\*b\*TP\*RT + + b\*b\*RT\*RT. Where intercept, TP, RT, TP\*RT, TP \*TP, RT\*RT are the parameters evaluated and presented in the primary outcomes 5, 6 and 7. And a and b are parameters (hour) corresponding respectively to the TP and the RT where the prediction has to be done. This outcome is presenting TP and RT estimates expressed as log(hours). The optimum of this Design of Experiment (DOE) is presented in outcome 8. |
| Lymphocytes Viability Prediction (Non-transformed Estimate) in CMI Samples Post-overnight Incubation Time Before ICS: TP*RT and RT*RT Parameter Estimates of the Prediction Model - Condition None Resting Time Included | At Day 15 (sample collection visit) | The objective was to model lymphocyte viability according to time-to-process (TP=2h, 7h or 24h) and resting time (RT=0h) conditions in order to select the best combination of these two parameters with the aim to maximize the post-ICS viability in CMI samples collected from ART-naïve HIV-1-infected subjects. Viability (%) = 10 \^ P / (1 + 10 \^ P) \* 100 with P for Prediction. The optimum of the viability was predicted as follows. P (LOGIT)= intercept + a\*TP + b\*RT + a\*b\*TP\*RT + + b\*b\*RT\*RT. Where intercept, TP, RT, TP\*RT, TP \*TP, RT\*RT are the parameters evaluated and presented in the primary outcomes 5, 6 and 7. And a and b are parameters (hour) corresponding respectively to the TP and the RT where the prediction has to be done. This outcome is presenting TP\*RT and RT\*RT estimates expressed as log(hours\^2). The optimum of this DOE is presented in outcome 8. |
| Lymphocytes Viability Prediction (LOGIT Transformed) in CMI Samples Post-overnight Incubation Time Before Intracellular Cytokine Staining (ICS): Intercept Parameter Estimate of the Prediction Model - Condition None Resting Time Not Included | At Day 15 (sample collection visit) | The objective was to model lymphocyte viability according to time-to-process (TP=2h, 7h or 24h) and resting time (RT=2h, 6h or 18h \[none resting time not included\]) conditions to select the best combination of these two parameters to maximize the post-ICS viability in CMI samples collected from ART-naïve HIV-1-infected subjects. Viability (%) = 10\^P/(1 + 10\^P)\*100 with P for Prediction.The optimum of the viability was predicted as P (LOGIT)= intercept + a\*TP + b\*RT + a\*b\*TP\*RT + a\*a\*TP\*TP + b\*b\*RT\*RT. Where intercept, TP, RT, TP\*RT, TP \*TP, RT\*RT are the parameters evaluated and presented in the 3 first primary outcomes. And a and b are log-transformed parameters corresponding respectively to the TP and the RT where the prediction has to be done. This outcome is presenting the intercept i.e. expected mean value of Prediction when TP and RT = 0. The optimum of this Design of Experiment is presented in outcome 4. |
| Lymphocytes Viability Prediction (LOGIT Transformed Estimate) in CMI Samples Post-overnight Incubation Time Before ICS: Time to Process and Resting Time Parameter Estimates of the Prediction Model - Condition None Resting Time Not Included | At Day 15 (sample collection visit) | The objective was to model lymphocyte viability according to time-to-process (TP=2h, 7h or 24h) and resting time (RT=2h, 6h or 18h \[none resting time not included\]) conditions to select the best combination of these two parameters to maximize the post-ICS viability in CMI samples collected from ART-naïve HIV-1-infected subjects. Viability (%) = 10 \^ P / (1 + 10 \^ P) \* 100 with P for Prediction.The optimum of the viability was predicted as P (LOGIT)= intercept + a\*TP + b\*RT + a\*b\*TP\*RT + a\*a\*TP\*TP + b\*b\*RT\*RT. Where intercept, TP, RT, TP\*RT, TP \*TP, RT\*RT are the parameters evaluated and presented in the 3 first primary outcomes. And a and b are log-transformed parameters corresponding respectively to the TP and the RT where the prediction has to be done. This outcome is presenting TP and RT estimates expressed as log(hours). The optimum of this Design of Experiment (DOE) is presented in outcome 4. |
| Lymphocytes Viability Prediction (LOGIT Transformed Estimate) in CMI Samples Post-overnight Incubation Time Before ICS: TP*RT, TP*TP and RT*RT Parameter Estimates of the Prediction Model - Condition None Resting Time Not Included | At Day 15 (sample collection visit) | The objective was to model lymphocyte viability according to time-to-process (TP=2h, 7h or 24h) and resting time (RT=2h, 6h or 18h \[none resting time not included\]) conditions to select the best combination of these two parameters to maximize the post-ICS viability in CMI samples collected from ART-naïve HIV-1-infected subjects. Viability (%) = 10 \^ P / (1 + 10 \^ P) \* 100 with P for Prediction.The optimum of the viability was predicted as P (LOGIT)= intercept + a\*TP + b\*RT + a\*b\*TP\*RT + a\*a\*TP\*TP + b\*b\*RT\*RT. Where intercept, TP, RT, TP\*RT, TP \*TP, RT\*RT are the parameters evaluated and presented in the 3 first primary outcomes. And a and b are log-transformed parameters corresponding respectively to the TP and the RT where the prediction has to be done. This outcome is presenting TP\*RT, TP\*TP and RT\*RT estimates expressed as log(hours\^2). The optimum of this DOE is presented in outcome 4. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Magnitude of HIV-1 RT Specific Cluster of Differentiation 40 Ligand (CD40L+) CD4+ T Cell Responses in the CMI Samples Post-overnight ICS/Post 6 Hour ICS, Expressing at Least One Cytokine | At Day 15 (sample collection visit) | Data were collected but could not be reported as data were below level of detection. |
| Magnitude of HIV-RT Specific (Background Reduced) CD8+ T Cell Responses in the CMI Samples Post-overnight ICS/Post 6 Hour ICS, Expressing at Least One Cytokine | At Day 15 (sample collection visit) | HIV-RT specific responses of CD8+ T cells expressing at least one cytokine, among: Interleukin-2 (IL-2), Interferon-gamma (IFN-g) and Tumor necrosis factor alpha (TNF-a),after stimulation with HIV-1 peptide pools for time-to-process (TP) (2, 7, 24 hours) and resting time (RT) (0,2,6,18 hours) post-overnight ICS and for time-to-process (7 hours) and resting time (18 hours) post 6 hours ICS. |
| Number of Subjects With Serious Adverse Events (SAEs) | During the whole study period (From Day 0 to Day 15) | Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitali-zation or prolongation of hospitalization or result in disability/incapacity. |
| Percentage of Viable Lymphocytes in the CMI Samples, Post-overnight Incubation (Classic) Before ICS and Post-6 Hour Incubation Before ICS | A Day 15 (sample collection visit) | The percentage of viable lymphocytes was determined by Forward Scatter/Side Scatter (FSC/SSC) and LIVE/DEAD gating during flow cytometry analysis for each incubation of time-to-time process (TP) = 2h, 7h and 24 h and resting time (RT) = 18h for the comparison of resting time = 18h and classic incubation time versus resting time = 18h and post-6h incubation time. |
Countries
Belgium
Participant flow
Pre-assignment details
Of 31 subjects registered in the study, 9 subjects were screen failures and 22 subjects were enrolled in the study.
Participants by arm
| Arm | Count |
|---|---|
| HIV-1 Group Antiretroviral Therapy-naïve HIV1-infected subjects, aged 18 to 55 years, from whom samples for cell-mediated immunity (CMI) were collected. No investigational vaccine was administered. | 22 |
| Total | 22 |
Baseline characteristics
| Characteristic | HIV-1 Group |
|---|---|
| Age, Continuous | 36.8 years STANDARD_DEVIATION 9.05 |
| Race/Ethnicity, Customized Race African heritage / African American | 1 Participants |
| Race/Ethnicity, Customized Race Asian - East Asian heritage | 1 Participants |
| Race/Ethnicity, Customized Race White - Caucasian / European heritage | 20 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 22 |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 0 / 22 |
Outcome results
Primary
Lymphocytes Viability Prediction (LOGIT Transformed Estimate) in CMI Samples Post-overnight Incubation Time Before ICS: Optimum Mean Cell Viability Estimate by the Prediction Model - Condition None Resting Time Not Included
The objective was to model lymphocyte viability according to time-to-process (TP=2h, 7h or 24h) and resting time (RT=2h, 6h or 18h \[none resting time not included\]) conditions to select the best combination of these two parameters to maximize the post-ICS viability in CMI samples collected from ART-naïve HIV-1-infected subjects. Viability (%) = 10 \^ P / (1 + 10 \^ P) \* 100 with P for Prediction.The optimum of the viability was predicted as P (LOGIT)= intercept + a\*TP + b\*RT + a\*b\*TP\*RT + a\*a\*TP\*TP + b\*b\*RT\*RT. Where intercept, TP, RT, TP\*RT, TP \*TP, RT\*RT are the parameters evaluated and presented in the 3 first primary outcomes. And a and b are log-transformed parameters corresponding respectively to the TP and the RT where the prediction has to be done. The optimum predicted mean cell viability of this Design of Experiment is presented in this outcome and expressed as percentage.
Time frame: At Day 15 (sample collection visit)
Population: The analysis was performed on the According to Protocol (ATP) Sample Collection cohort, which included all subjects accepted into the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HIV-1 Group | Lymphocytes Viability Prediction (LOGIT Transformed Estimate) in CMI Samples Post-overnight Incubation Time Before ICS: Optimum Mean Cell Viability Estimate by the Prediction Model - Condition None Resting Time Not Included | 89.69 Percentage of viable lymphocytes |
Primary
Lymphocytes Viability Prediction (LOGIT Transformed Estimate) in CMI Samples Post-overnight Incubation Time Before ICS: Time to Process and Resting Time Parameter Estimates of the Prediction Model - Condition None Resting Time Not Included
The objective was to model lymphocyte viability according to time-to-process (TP=2h, 7h or 24h) and resting time (RT=2h, 6h or 18h \[none resting time not included\]) conditions to select the best combination of these two parameters to maximize the post-ICS viability in CMI samples collected from ART-naïve HIV-1-infected subjects. Viability (%) = 10 \^ P / (1 + 10 \^ P) \* 100 with P for Prediction.The optimum of the viability was predicted as P (LOGIT)= intercept + a\*TP + b\*RT + a\*b\*TP\*RT + a\*a\*TP\*TP + b\*b\*RT\*RT. Where intercept, TP, RT, TP\*RT, TP \*TP, RT\*RT are the parameters evaluated and presented in the 3 first primary outcomes. And a and b are log-transformed parameters corresponding respectively to the TP and the RT where the prediction has to be done. This outcome is presenting TP and RT estimates expressed as log(hours). The optimum of this Design of Experiment (DOE) is presented in outcome 4.
Time frame: At Day 15 (sample collection visit)
Population: The analysis was performed on the According to Protocol (ATP) Sample Collection cohort, which included all subjects accepted into the analysis.
| Arm | Measure | Group | Value (LOG_MEAN) | Dispersion |
|---|---|---|---|---|
| HIV-1 Group | Lymphocytes Viability Prediction (LOGIT Transformed Estimate) in CMI Samples Post-overnight Incubation Time Before ICS: Time to Process and Resting Time Parameter Estimates of the Prediction Model - Condition None Resting Time Not Included | TP | 0.1724 Log(hours) | Standard Error 0.1152 |
| HIV-1 Group | Lymphocytes Viability Prediction (LOGIT Transformed Estimate) in CMI Samples Post-overnight Incubation Time Before ICS: Time to Process and Resting Time Parameter Estimates of the Prediction Model - Condition None Resting Time Not Included | RT | 0.9578 Log(hours) | Standard Error 0.1342 |
Primary
Lymphocytes Viability Prediction (LOGIT Transformed Estimate) in CMI Samples Post-overnight Incubation Time Before ICS: TP*RT, TP*TP and RT*RT Parameter Estimates of the Prediction Model - Condition None Resting Time Not Included
The objective was to model lymphocyte viability according to time-to-process (TP=2h, 7h or 24h) and resting time (RT=2h, 6h or 18h \[none resting time not included\]) conditions to select the best combination of these two parameters to maximize the post-ICS viability in CMI samples collected from ART-naïve HIV-1-infected subjects. Viability (%) = 10 \^ P / (1 + 10 \^ P) \* 100 with P for Prediction.The optimum of the viability was predicted as P (LOGIT)= intercept + a\*TP + b\*RT + a\*b\*TP\*RT + a\*a\*TP\*TP + b\*b\*RT\*RT. Where intercept, TP, RT, TP\*RT, TP \*TP, RT\*RT are the parameters evaluated and presented in the 3 first primary outcomes. And a and b are log-transformed parameters corresponding respectively to the TP and the RT where the prediction has to be done. This outcome is presenting TP\*RT, TP\*TP and RT\*RT estimates expressed as log(hours\^2). The optimum of this DOE is presented in outcome 4.
Time frame: At Day 15 (sample collection visit)
Population: The analysis was performed on the According to Protocol (ATP) Sample Collection cohort, which included all subjects accepted into the analysis.
| Arm | Measure | Group | Value (LOG_MEAN) | Dispersion |
|---|---|---|---|---|
| HIV-1 Group | Lymphocytes Viability Prediction (LOGIT Transformed Estimate) in CMI Samples Post-overnight Incubation Time Before ICS: TP*RT, TP*TP and RT*RT Parameter Estimates of the Prediction Model - Condition None Resting Time Not Included | TP*RT | 0.1120 Log(hours^2) | Standard Error 0.05041 |
| HIV-1 Group | Lymphocytes Viability Prediction (LOGIT Transformed Estimate) in CMI Samples Post-overnight Incubation Time Before ICS: TP*RT, TP*TP and RT*RT Parameter Estimates of the Prediction Model - Condition None Resting Time Not Included | TP*TP | -0.2934 Log(hours^2) | Standard Error 0.06426 |
| HIV-1 Group | Lymphocytes Viability Prediction (LOGIT Transformed Estimate) in CMI Samples Post-overnight Incubation Time Before ICS: TP*RT, TP*TP and RT*RT Parameter Estimates of the Prediction Model - Condition None Resting Time Not Included | RT*RT | -0.9364 Log(hours^2) | Standard Error 0.08133 |
Primary
Lymphocytes Viability Prediction (LOGIT Transformed) in CMI Samples Post-overnight Incubation Time Before Intracellular Cytokine Staining (ICS): Intercept Parameter Estimate of the Prediction Model - Condition None Resting Time Not Included
The objective was to model lymphocyte viability according to time-to-process (TP=2h, 7h or 24h) and resting time (RT=2h, 6h or 18h \[none resting time not included\]) conditions to select the best combination of these two parameters to maximize the post-ICS viability in CMI samples collected from ART-naïve HIV-1-infected subjects. Viability (%) = 10\^P/(1 + 10\^P)\*100 with P for Prediction.The optimum of the viability was predicted as P (LOGIT)= intercept + a\*TP + b\*RT + a\*b\*TP\*RT + a\*a\*TP\*TP + b\*b\*RT\*RT. Where intercept, TP, RT, TP\*RT, TP \*TP, RT\*RT are the parameters evaluated and presented in the 3 first primary outcomes. And a and b are log-transformed parameters corresponding respectively to the TP and the RT where the prediction has to be done. This outcome is presenting the intercept i.e. expected mean value of Prediction when TP and RT = 0. The optimum of this Design of Experiment is presented in outcome 4.
Time frame: At Day 15 (sample collection visit)
Population: The analysis was performed on the According to Protocol (ATP) Sample Collection cohort, which included all subjects accepted into the analysis.
| Arm | Measure | Value (LOG_MEAN) | Dispersion |
|---|---|---|---|
| HIV-1 Group | Lymphocytes Viability Prediction (LOGIT Transformed) in CMI Samples Post-overnight Incubation Time Before Intracellular Cytokine Staining (ICS): Intercept Parameter Estimate of the Prediction Model - Condition None Resting Time Not Included | 0.6490 Unitless assessment of prediction | Standard Error 0.06989 |
Primary
Lymphocytes Viability Prediction (Non-transformed Estimate) in CMI Samples Post-overnight Incubation Time Before ICS: Intercept Parameter Estimate of the Prediction Model - Condition None Resting Time Included
The objective was to model lymphocyte viability according to time-to-process (TP=2h, 7h or 24h) and resting time (RT=0h) conditions in order to select the best combination of these two parameters with the aim to maximize the post-ICS viability in CMI samples collected from ART-naïve HIV-1-infected subjects. Viability (%) = 10 \^ P / (1 + 10 \^ P) \* 100 with P for Prediction. The optimum of the viability was predicted as follows. P (LOGIT)= intercept + a\*TP + b\*RT + a\*b\*TP\*RT + + b\*b\*RT\*RT. Where intercept, TP, RT, TP\*RT, TP \*TP, RT\*RT are the parameters evaluated and presented in the primary outcomes 5, 6 and 7. And a and b are parameters (hour) corresponding respectively to the TP and the RT where the prediction has to be done. This outcome is presenting the intercept i.e. expected mean value of Prediction when TP and RT = 0. The optimum of this Design of Experiment is presented in outcome 8.
Time frame: At Day 15 (sample collection visit)
Population: The analysis was performed on the According to Protocol (ATP) Sample Collection cohort, which included all subjects accepted into the analysis.
| Arm | Measure | Value (LOG_MEAN) | Dispersion |
|---|---|---|---|
| HIV-1 Group | Lymphocytes Viability Prediction (Non-transformed Estimate) in CMI Samples Post-overnight Incubation Time Before ICS: Intercept Parameter Estimate of the Prediction Model - Condition None Resting Time Included | 0.8145 Unitless assessment of prediction | Standard Error 0.03753 |
Primary
Lymphocytes Viability Prediction (Non-transformed Estimate) in CMI Samples Post-overnight Incubation Time Before ICS: Optimum Mean Cell Viability Estimates by the Prediction Model -Condition None Resting Time Included.
The objective was to model lymphocyte viability according to time-to-process (TP=2h, 7h or 24h) and resting time (RT=0h) conditions in order to select the best combination of these two parameters with the aim to maximize the post-ICS viability in CMI samples collected from ART-naïve HIV-1-infected subjects. Viability (%) = 10 \^ P / (1 + 10 \^ P) \* 100 with P for Prediction. The optimum of the viability was predicted as follows. P (LOGIT)= intercept + a\*TP + b\*RT + a\*b\*TP\*RT + + b\*b\*RT\*RT. Where intercept, TP, RT, TP\*RT, TP \*TP, RT\*RT are the parameters evaluated and presented in the primary outcomes 5, 6 and 7. And a and b are parameters (hour) corresponding respectively to the TP and the RT where the prediction has to be done. The optimum predicted mean cell viability of this Design of Experiment is presented in this outcome and expressed as percentage.
Time frame: At Day 15 (sample collection visit)
Population: The analysis was performed on the According to Protocol (ATP) Sample Collection cohort, which included all subjects accepted into the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HIV-1 Group | Lymphocytes Viability Prediction (Non-transformed Estimate) in CMI Samples Post-overnight Incubation Time Before ICS: Optimum Mean Cell Viability Estimates by the Prediction Model -Condition None Resting Time Included. | 89.49 Percentage of viable lymphocytes |
Primary
Lymphocytes Viability Prediction (Non-transformed Estimate) in CMI Samples Post-overnight Incubation Time Before ICS: Time to Process and Resting Time Parameter Estimates of the Prediction Model - Condition None Resting Time Included
The objective was to model lymphocyte viability according to time-to-process (TP=2h, 7h or 24h) and resting time (RT=0h) conditions in order to select the best combination of these two parameters with the aim to maximize the post-ICS viability in CMI samples collected from ART-naïve HIV-1-infected subjects. Viability (%) = 10 \^ P / (1 + 10 \^ P) \* 100 with P for Prediction. The optimum of the viability was predicted as follows. P (LOGIT)= intercept + a\*TP + b\*RT + a\*b\*TP\*RT + + b\*b\*RT\*RT. Where intercept, TP, RT, TP\*RT, TP \*TP, RT\*RT are the parameters evaluated and presented in the primary outcomes 5, 6 and 7. And a and b are parameters (hour) corresponding respectively to the TP and the RT where the prediction has to be done. This outcome is presenting TP and RT estimates expressed as log(hours). The optimum of this Design of Experiment (DOE) is presented in outcome 8.
Time frame: At Day 15 (sample collection visit)
Population: The analysis was performed on the According to Protocol (ATP) Sample Collection cohort, which included all subjects accepted into the analysis.
| Arm | Measure | Group | Value (LOG_MEAN) | Dispersion |
|---|---|---|---|---|
| HIV-1 Group | Lymphocytes Viability Prediction (Non-transformed Estimate) in CMI Samples Post-overnight Incubation Time Before ICS: Time to Process and Resting Time Parameter Estimates of the Prediction Model - Condition None Resting Time Included | TP | -0.01853 Log(hours) | Standard Error 0.001194 |
| HIV-1 Group | Lymphocytes Viability Prediction (Non-transformed Estimate) in CMI Samples Post-overnight Incubation Time Before ICS: Time to Process and Resting Time Parameter Estimates of the Prediction Model - Condition None Resting Time Included | RT | 0.04616 Log(hours) | Standard Error 0.005642 |
Primary
Lymphocytes Viability Prediction (Non-transformed Estimate) in CMI Samples Post-overnight Incubation Time Before ICS: TP*RT and RT*RT Parameter Estimates of the Prediction Model - Condition None Resting Time Included
The objective was to model lymphocyte viability according to time-to-process (TP=2h, 7h or 24h) and resting time (RT=0h) conditions in order to select the best combination of these two parameters with the aim to maximize the post-ICS viability in CMI samples collected from ART-naïve HIV-1-infected subjects. Viability (%) = 10 \^ P / (1 + 10 \^ P) \* 100 with P for Prediction. The optimum of the viability was predicted as follows. P (LOGIT)= intercept + a\*TP + b\*RT + a\*b\*TP\*RT + + b\*b\*RT\*RT. Where intercept, TP, RT, TP\*RT, TP \*TP, RT\*RT are the parameters evaluated and presented in the primary outcomes 5, 6 and 7. And a and b are parameters (hour) corresponding respectively to the TP and the RT where the prediction has to be done. This outcome is presenting TP\*RT and RT\*RT estimates expressed as log(hours\^2). The optimum of this DOE is presented in outcome 8.
Time frame: At Day 15 (sample collection visit)
Population: The analysis was performed on the According to Protocol (ATP) Sample Collection cohort, which included all subjects accepted into the analysis.
| Arm | Measure | Group | Value (LOG_MEAN) | Dispersion |
|---|---|---|---|---|
| HIV-1 Group | Lymphocytes Viability Prediction (Non-transformed Estimate) in CMI Samples Post-overnight Incubation Time Before ICS: TP*RT and RT*RT Parameter Estimates of the Prediction Model - Condition None Resting Time Included | TP*RT | 0.000588 Log(hours^2) | Standard Error 0.000121 |
| HIV-1 Group | Lymphocytes Viability Prediction (Non-transformed Estimate) in CMI Samples Post-overnight Incubation Time Before ICS: TP*RT and RT*RT Parameter Estimates of the Prediction Model - Condition None Resting Time Included | RT*RT | -0.00367 Log(hours^2) | Standard Error 0.000284 |
Secondary
Magnitude of HIV-1 RT Specific Cluster of Differentiation 40 Ligand (CD40L+) CD4+ T Cell Responses in the CMI Samples Post-overnight ICS/Post 6 Hour ICS, Expressing at Least One Cytokine
Data were collected but could not be reported as data were below level of detection.
Time frame: At Day 15 (sample collection visit)
Population: The analysis was to be performed on the According to Protocol (ATP) Sample Collection cohort. Data were collected but could not be reported as data were below the detection level.
Secondary
Magnitude of HIV-RT Specific (Background Reduced) CD8+ T Cell Responses in the CMI Samples Post-overnight ICS/Post 6 Hour ICS, Expressing at Least One Cytokine
HIV-RT specific responses of CD8+ T cells expressing at least one cytokine, among: Interleukin-2 (IL-2), Interferon-gamma (IFN-g) and Tumor necrosis factor alpha (TNF-a),after stimulation with HIV-1 peptide pools for time-to-process (TP) (2, 7, 24 hours) and resting time (RT) (0,2,6,18 hours) post-overnight ICS and for time-to-process (7 hours) and resting time (18 hours) post 6 hours ICS.
Time frame: At Day 15 (sample collection visit)
Population: The analysis was performed on the According to Protocol (ATP) Sample Collection cohort, which included all subjects accepted into the analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| HIV-1 Group | Magnitude of HIV-RT Specific (Background Reduced) CD8+ T Cell Responses in the CMI Samples Post-overnight ICS/Post 6 Hour ICS, Expressing at Least One Cytokine | TP 2h RT 0h post-overnight ICS | 0.257075 Percentage of CD8+ T cells |
| HIV-1 Group | Magnitude of HIV-RT Specific (Background Reduced) CD8+ T Cell Responses in the CMI Samples Post-overnight ICS/Post 6 Hour ICS, Expressing at Least One Cytokine | TP 2h RT 2h post-overnight ICS | 0.2757 Percentage of CD8+ T cells |
| HIV-1 Group | Magnitude of HIV-RT Specific (Background Reduced) CD8+ T Cell Responses in the CMI Samples Post-overnight ICS/Post 6 Hour ICS, Expressing at Least One Cytokine | TP 2h RT 6h post-overnight ICS | 0.3059 Percentage of CD8+ T cells |
| HIV-1 Group | Magnitude of HIV-RT Specific (Background Reduced) CD8+ T Cell Responses in the CMI Samples Post-overnight ICS/Post 6 Hour ICS, Expressing at Least One Cytokine | TP 2h RT 18h post-overnight ICS | 0.3114 Percentage of CD8+ T cells |
| HIV-1 Group | Magnitude of HIV-RT Specific (Background Reduced) CD8+ T Cell Responses in the CMI Samples Post-overnight ICS/Post 6 Hour ICS, Expressing at Least One Cytokine | TP 7h RT 0h post-overnight ICS | 0.23485 Percentage of CD8+ T cells |
| HIV-1 Group | Magnitude of HIV-RT Specific (Background Reduced) CD8+ T Cell Responses in the CMI Samples Post-overnight ICS/Post 6 Hour ICS, Expressing at Least One Cytokine | TP 7h RT 2h post-overnight ICS | 0.2761 Percentage of CD8+ T cells |
| HIV-1 Group | Magnitude of HIV-RT Specific (Background Reduced) CD8+ T Cell Responses in the CMI Samples Post-overnight ICS/Post 6 Hour ICS, Expressing at Least One Cytokine | TP 7h RT 6h post-overnight ICS | 0.2615 Percentage of CD8+ T cells |
| HIV-1 Group | Magnitude of HIV-RT Specific (Background Reduced) CD8+ T Cell Responses in the CMI Samples Post-overnight ICS/Post 6 Hour ICS, Expressing at Least One Cytokine | TP 7h RT 18h post-overnight ICS | 0.35455 Percentage of CD8+ T cells |
| HIV-1 Group | Magnitude of HIV-RT Specific (Background Reduced) CD8+ T Cell Responses in the CMI Samples Post-overnight ICS/Post 6 Hour ICS, Expressing at Least One Cytokine | TP 7h RT 18h post 6h ICS | 0.117 Percentage of CD8+ T cells |
| HIV-1 Group | Magnitude of HIV-RT Specific (Background Reduced) CD8+ T Cell Responses in the CMI Samples Post-overnight ICS/Post 6 Hour ICS, Expressing at Least One Cytokine | TP 24h RT 0h post-overnight ICS | 0.18731 Percentage of CD8+ T cells |
| HIV-1 Group | Magnitude of HIV-RT Specific (Background Reduced) CD8+ T Cell Responses in the CMI Samples Post-overnight ICS/Post 6 Hour ICS, Expressing at Least One Cytokine | TP 24h RT 2h post-overnight ICS | 0.29285 Percentage of CD8+ T cells |
| HIV-1 Group | Magnitude of HIV-RT Specific (Background Reduced) CD8+ T Cell Responses in the CMI Samples Post-overnight ICS/Post 6 Hour ICS, Expressing at Least One Cytokine | TP 24h RT 6h post-overnight ICS | 0.2496 Percentage of CD8+ T cells |
| HIV-1 Group | Magnitude of HIV-RT Specific (Background Reduced) CD8+ T Cell Responses in the CMI Samples Post-overnight ICS/Post 6 Hour ICS, Expressing at Least One Cytokine | TP 24h RT 18h post-overnight ICS | 0.3663 Percentage of CD8+ T cells |
Secondary
Number of Subjects With Serious Adverse Events (SAEs)
Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitali-zation or prolongation of hospitalization or result in disability/incapacity.
Time frame: During the whole study period (From Day 0 to Day 15)
Population: The analysis was performed on the Total eligible cohort which included all subjects in the Total cohort (all enrolled subjects) who fulfilled eligibility criteria.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HIV-1 Group | Number of Subjects With Serious Adverse Events (SAEs) | 0 Participants |
Secondary
Percentage of Viable Lymphocytes in the CMI Samples, Post-overnight Incubation (Classic) Before ICS and Post-6 Hour Incubation Before ICS
The percentage of viable lymphocytes was determined by Forward Scatter/Side Scatter (FSC/SSC) and LIVE/DEAD gating during flow cytometry analysis for each incubation of time-to-time process (TP) = 2h, 7h and 24 h and resting time (RT) = 18h for the comparison of resting time = 18h and classic incubation time versus resting time = 18h and post-6h incubation time.
Time frame: A Day 15 (sample collection visit)
Population: The analysis was performed on the According to Protocol (ATP) Sample Collection cohort, which included all subjects accepted into the analysis.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| HIV-1 Group | Percentage of Viable Lymphocytes in the CMI Samples, Post-overnight Incubation (Classic) Before ICS and Post-6 Hour Incubation Before ICS | TP=2h; RT=18h; post 6h incubation | 82.30 Percentage of viable lymphocytes |
| HIV-1 Group | Percentage of Viable Lymphocytes in the CMI Samples, Post-overnight Incubation (Classic) Before ICS and Post-6 Hour Incubation Before ICS | TP=2h; RT=18h; classic incubation | 72.72 Percentage of viable lymphocytes |
| HIV-1 Group | Percentage of Viable Lymphocytes in the CMI Samples, Post-overnight Incubation (Classic) Before ICS and Post-6 Hour Incubation Before ICS | TP=7h; RT=18h; post 6h incubation | 82.49 Percentage of viable lymphocytes |
| HIV-1 Group | Percentage of Viable Lymphocytes in the CMI Samples, Post-overnight Incubation (Classic) Before ICS and Post-6 Hour Incubation Before ICS | TP=7h; RT=18h; classic incubation | 73.65 Percentage of viable lymphocytes |
| HIV-1 Group | Percentage of Viable Lymphocytes in the CMI Samples, Post-overnight Incubation (Classic) Before ICS and Post-6 Hour Incubation Before ICS | TP=24h; RT=18h; post 6h incubation | 72.64 Percentage of viable lymphocytes |
| HIV-1 Group | Percentage of Viable Lymphocytes in the CMI Samples, Post-overnight Incubation (Classic) Before ICS and Post-6 Hour Incubation Before ICS | TP=24h; RT=18h; classic incubation | 64.60 Percentage of viable lymphocytes |