Optimizing the Quality of Samples Used for the Evaluation of Cell-mediated Immune (CMI) Responses in Antiretroviral Therapy (ART)-naïve Human Deficiency Virus Type 1 (HIV-1)-Infected Subjects
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- 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
研究概览
简要总结
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.
详细描述
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"].
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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-
- •This includes subjects with dual infection with HIV-1/HIV-
- •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
- •Pregnant or lactating female.
研究组 & 干预措施
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.
干预措施: Blood sample collection (Procedure)
结局指标
主要结局
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
时间窗: 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 (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
时间窗: 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 (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
时间窗: 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 (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.
时间窗: 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: TP*RT, TP*TP and RT*RT Parameter Estimates of the Prediction Model - Condition "None" Resting Time Not Included
时间窗: 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.
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
时间窗: 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 (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
时间窗: 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 (Non-transformed Estimate) in CMI Samples Post-overnight Incubation Time Before ICS: "Intercept" Parameter Estimate of the Prediction Model - Condition "None" Resting Time Included
时间窗: 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.
次要结局
- 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))
- Number of Subjects With Serious Adverse Events (SAEs)(During the whole study period (From Day 0 to Day 15))
- 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))
- 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))