NCT01610427

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

Completed NA Results posted Last updated 24 April 2020

What this trial tests

NA trial testing Blood sample collection in AIDS in 22 participants. Completed in 30 October 2012.

Timeline

25 June 2012

Primary endpoint
30 October 2012

30 October 2012

Quick facts

Lead sponsor	GlaxoSmithKline
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	basic science
Enrollment	22
Start date	25 June 2012
Primary completion	30 October 2012
Estimated completion	30 October 2012
Sites	1 location across Belgium

Drugs / interventions tested

• Blood sample collection — full drug profile →

Conditions studied

• AIDS — all drugs for AIDS →
• AIDS Vaccines — all drugs for AIDS Vaccines →

Sponsor

GlaxoSmithKline — full company profile →

Who can join

Adults 18 to 55, any sex, with AIDS or AIDS Vaccines. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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 Primary · 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 pa

Group	Value	95% CI
HIV-1 Group	0.6490	± 0.06989

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 Primary · 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" ar

TP

Group	Value	95% CI
HIV-1 Group	0.1724	± 0.1152

RT

Group	Value	95% CI
HIV-1 Group	0.9578	± 0.1342

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 Primary · 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" ar

TP*RT

Group	Value	95% CI
HIV-1 Group	0.1120	± 0.05041

TP*TP

Group	Value	95% CI
HIV-1 Group	-0.2934	± 0.06426

RT*RT

Group	Value	95% CI
HIV-1 Group	-0.9364	± 0.08133

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 Primary · 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" ar

Group	Value	95% CI
HIV-1 Group	89.69

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 Primary · 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 an

Group	Value	95% CI
HIV-1 Group	0.8145	± 0.03753

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 Primary · 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 an

TP

Group	Value	95% CI
HIV-1 Group	-0.01853	± 0.001194

RT

Group	Value	95% CI
HIV-1 Group	0.04616	± 0.005642

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 Primary · 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 an

TP*RT

Group	Value	95% CI
HIV-1 Group	0.000588	± 0.000121

RT*RT

Group	Value	95% CI
HIV-1 Group	-0.00367	± 0.000284

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. Primary · 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 an

Group	Value	95% CI
HIV-1 Group	89.49

Percentage of Viable Lymphocytes in the CMI Samples, Post-overnight Incubation (Classic) Before ICS and Post-6 Hour Incubation Before ICS Secondary · 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.

TP=2h; RT=18h; post 6h incubation

Group	Value	95% CI
HIV-1 Group	82.30	79.57 – 84.74

TP=2h; RT=18h; classic incubation

Group	Value	95% CI
HIV-1 Group	72.72	69.07 – 76.09

TP=7h; RT=18h; post 6h incubation

Group	Value	95% CI
HIV-1 Group	82.49	76.09 – 84.97

TP=7h; RT=18h; classic incubation

Group	Value	95% CI
HIV-1 Group	73.65	70.00 – 77.01

TP=24h; RT=18h; post 6h incubation

Group	Value	95% CI
HIV-1 Group	72.64	68.83 – 76.15

TP=24h; RT=18h; classic incubation

Group	Value	95% CI
HIV-1 Group	64.60	60.41 – 68.58

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 Secondary · 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.

TP 2h RT 0h post-overnight ICS

Group	Value	95% CI
HIV-1 Group	0.257075	0.165275 – 0.492275

TP 2h RT 2h post-overnight ICS

Group	Value	95% CI
HIV-1 Group	0.2757	0.193275 – 0.56075

TP 2h RT 6h post-overnight ICS

Group	Value	95% CI
HIV-1 Group	0.3059	0.122015 – 0.465168

TP 2h RT 18h post-overnight ICS

Group	Value	95% CI
HIV-1 Group	0.3114	0.1855 – 0.946325

TP 7h RT 0h post-overnight ICS

Group	Value	95% CI
HIV-1 Group	0.23485	0.10595 – 0.44535

TP 7h RT 2h post-overnight ICS

Group	Value	95% CI
HIV-1 Group	0.2761	0.16446 – 0.54085

TP 7h RT 6h post-overnight ICS

Group	Value	95% CI
HIV-1 Group	0.2615	0.141975 – 0.6853

TP 7h RT 18h post-overnight ICS

Group	Value	95% CI
HIV-1 Group	0.35455	0.220358 – 0.8207

Number of Subjects With Serious Adverse Events (SAEs) Secondary · 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.

Group	Value	95% CI
HIV-1 Group	0

Sponsor's own description

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.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Processing of blood samples influences PBMC viability and outcome of cell-mediated immune responses in antiretroviral therapy-naïve HIV-1-infected patients.
   Bourguignon P, Clément F, Renaud F, Le Bras V, et al · · 2014 · cited 16× · PMID 25224748 · DOI 10.1016/j.jim.2014.09.001
2. Post-Immune Antibodies in HIV-1 Infection in the Context of Vaccine Development: A Variety of Biological Functions and Catalytic Activities.
   Timofeeva A, Sedykh S, Nevinsky G. · · 2022 · cited 12× · PMID 35335016 · DOI 10.3390/vaccines10030384