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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.
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"].
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| HIV-1 Group | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Blood sample collection | Procedure | 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) |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | At Day 15 (sample collection visit) |
| 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. | At Day 15 (sample collection visit) |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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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:
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:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Ghent | 9000 | Belgium |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25224748 | Derived | Bourguignon P, Clement F, Renaud F, Le Bras V, Koutsoukos M, Burny W, Moris P, Lorin C, Collard A, Leroux-Roels G, Roman F, Janssens M, Vandekerckhove L. Processing of blood samples influences PBMC viability and outcome of cell-mediated immune responses in antiretroviral therapy-naive HIV-1-infected patients. J Immunol Methods. 2014 Dec 1;414:1-10. doi: 10.1016/j.jim.2014.09.001. Epub 2014 Sep 16. |
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Of 31 subjects registered in the study, 9 subjects were screen failures and 22 subjects were enrolled in the study.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | The analysis was performed on the According to Protocol (ATP) Sample Collection cohort, which included all subjects accepted into the analysis. | Posted | Log Mean | Standard Error | Unitless assessment of prediction | At Day 15 (sample collection visit) |
SAEs: during the whole study period (From Day 0 to Day 15)
Only All-Cause Mortality and Serious Adverse Events were assessed. Other (Not Including Serious) Adverse Events were not monitored during this study period.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 866-435-7343 |
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| ID | Term |
|---|---|
| D000163 | Acquired Immunodeficiency Syndrome |
| ID | Term |
|---|---|
| D015658 | HIV Infections |
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
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| 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. | At Day 15 (sample collection visit) |
| 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. | At Day 15 (sample collection visit) |
| 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. | At Day 15 (sample collection visit) |
| 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. | At Day 15 (sample collection visit) |
| 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. | At Day 15 (sample collection visit) |
| 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. | At Day 15 (sample collection visit) |
| A Day 15 (sample collection visit) |
| 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. | At Day 15 (sample collection visit) |
| 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. | At Day 15 (sample collection visit) |
| 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. | During the whole study period (From Day 0 to Day 15) |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| 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. | The analysis was performed on the According to Protocol (ATP) Sample Collection cohort, which included all subjects accepted into the analysis. | Posted | Log Mean | Standard Error | Log(hours) | At Day 15 (sample collection visit) |
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| 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. | The analysis was performed on the According to Protocol (ATP) Sample Collection cohort, which included all subjects accepted into the analysis. | Posted | Log Mean | Standard Error | Log(hours^2) | At Day 15 (sample collection visit) |
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| 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. | The analysis was performed on the According to Protocol (ATP) Sample Collection cohort, which included all subjects accepted into the analysis. | Posted | Number | Percentage of viable lymphocytes | At Day 15 (sample collection visit) |
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| 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. | The analysis was performed on the According to Protocol (ATP) Sample Collection cohort, which included all subjects accepted into the analysis. | Posted | Log Mean | Standard Error | Unitless assessment of prediction | At Day 15 (sample collection visit) |
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| 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. | The analysis was performed on the According to Protocol (ATP) Sample Collection cohort, which included all subjects accepted into the analysis. | Posted | Log Mean | Standard Error | Log(hours) | At Day 15 (sample collection visit) |
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| 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. | The analysis was performed on the According to Protocol (ATP) Sample Collection cohort, which included all subjects accepted into the analysis. | Posted | Log Mean | Standard Error | Log(hours^2) | At Day 15 (sample collection visit) |
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| 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. | The analysis was performed on the According to Protocol (ATP) Sample Collection cohort, which included all subjects accepted into the analysis. | Posted | Number | Percentage of viable lymphocytes | At Day 15 (sample collection visit) |
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| 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. | The analysis was performed on the According to Protocol (ATP) Sample Collection cohort, which included all subjects accepted into the analysis. | Posted | Mean | 95% Confidence Interval | Percentage of viable lymphocytes | A Day 15 (sample collection visit) |
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| 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. | 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. | Posted | At Day 15 (sample collection visit) |
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| 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. | The analysis was performed on the According to Protocol (ATP) Sample Collection cohort, which included all subjects accepted into the analysis. | Posted | Median | Inter-Quartile Range | Percentage of CD8+ T cells | At Day 15 (sample collection visit) |
|
|
|
| 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. | The analysis was performed on the Total eligible cohort which included all subjects in the Total cohort (all enrolled subjects) who fulfilled eligibility criteria. | Posted | Count of Participants | Participants | During the whole study period (From Day 0 to Day 15) |
|
|
|
| 0 |
| 22 |
| 0 |
| 22 |
| 0 |
| 0 |
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
| D015229 |
| Sexually Transmitted Diseases, Viral |
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D012897 | Slow Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
| Title | Measurements |
|---|---|
|
|
| TP=7h; RT=18h; classic incubation |
|
| TP=24h; RT=18h; post 6h incubation |
|
| TP=24h; RT=18h; classic incubation |
|
|
| TP 2h RT 18h post-overnight ICS |
|
| TP 7h RT 0h post-overnight ICS |
|
| TP 7h RT 2h post-overnight ICS |
|
| TP 7h RT 6h post-overnight ICS |
|
| TP 7h RT 18h post-overnight ICS |
|
| TP 7h RT 18h post 6h ICS |
|
| TP 24h RT 0h post-overnight ICS |
|
| TP 24h RT 2h post-overnight ICS |
|
| TP 24h RT 6h post-overnight ICS |
|
| TP 24h RT 18h post-overnight ICS |
|