Study to Optimize the Quality of Samples for Cell-mediated Immunity (CMI) in ART-naïve HIV-1-infected Subjects

NCT01610427 | Completed Results

• 1 other identifier: 116329
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

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.

Conditions

AIDS; AIDS Vaccines

Keywords

CMI; Antiretroviral therapy-naïve; HIV

Outcome Measures

Primary Outcomes (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

  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)

• 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)

Secondary Outcomes (4)

• 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)

• 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)

Study Arms (1)

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.

Procedure: Blood sample collection

Interventions

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)

HIV-1 Group

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Ghent, 9000, Belgium

Location

Related Publications (1)

• 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.

  PMID: 25224748 DERIVED

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 31, 2012
• First Posted: June 4, 2012
• Study Start: June 25, 2012
• Primary Completion: October 30, 2012
• Study Completion: October 30, 2012
• Last Updated: April 24, 2020
• Results First Posted: April 24, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)