Clinical trial NCT01610427: Study to Optimize the Quality of Samples for Cell-mediated Immunity (CMI) in ART-naïve HIV-1-infected Subjects
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: AIDS
AIDS Vaccines
Keywords: CMI
Antiretroviral therapy-naïve
HIV
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2012-06-04
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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 \["resting -time"\].

Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: At Day 15 (sample collection visit)
measure: 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
timeFrame: At Day 15 (sample collection visit)
measure: 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
timeFrame: At Day 15 (sample collection visit)
measure: 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
timeFrame: At Day 15 (sample collection visit)
measure: 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
timeFrame: At Day 15 (sample collection visit)
measure: 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
timeFrame: At Day 15 (sample collection visit)
measure: 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
timeFrame: At Day 15 (sample collection visit)
measure: 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.
timeFrame: At Day 15 (sample collection visit)
Secondary outcomes:
measure: Percentage of Viable Lymphocytes in the CMI Samples, Post-overnight Incubation (Classic) Before ICS and Post-6 Hour Incubation Before ICS
timeFrame: A Day 15 (sample collection visit)
measure: 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
timeFrame: At Day 15 (sample collection visit)
measure: 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
timeFrame: At Day 15 (sample collection visit)
measure: Number of Subjects With Serious Adverse Events (SAEs)
timeFrame: During the whole study period (From Day 0 to Day 15)
Other outcomes:
Locations:
city: Gent
country: Belgium
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.