Efficacy and Safety of GSK Biologicals HIV Vaccine in Antiretroviral Therapy (ART)-naïve HIV-1 Infected Persons

Efficacy and Safety of HIV Vaccine 732462 in ART-naïve HIV-1 Infected Persons

This study is designed to determine whether administration of the GSK Biologicals HIV vaccine 732462 can lead to a reduction in viral load, and impact on the course of human immunodeficiency virus type 1 (HIV-1) infection. In HIV-1 infected persons who have not yet started antiretroviral therapy (ART), such a vaccine would potentially lead to a delay in the initiation of treatment.

Study Overview

• Status: Completed
• Conditions: AIDS
• Intervention / Treatment: Biological: GSK Biologicals HIV Vaccine 732462; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 191
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Bobigny, France, 93009
    • GSK Investigational Site
  • Créteil, France, 94010
    • GSK Investigational Site
  • Nantes, France, 44093
    • GSK Investigational Site
  • Paris, France, 75018
    • GSK Investigational Site
  • Paris, France, 75679
    • GSK Investigational Site
  • Paris Cedex 10, France, 75475
    • GSK Investigational Site
  • Paris Cedex 12, France, 75571
    • GSK Investigational Site
  • Paris Cedex 13, France, 75651
    • GSK Investigational Site
  • Paris Cedex 20, France, 75970
    • GSK Investigational Site
  • Paris cedex 15, France, 75908
    • GSK Investigational Site
• Germany
  • Berlin, Germany, 13353
    • GSK Investigational Site
  • Baden-Wuerttemberg
    • Freiburg, Baden-Wuerttemberg, Germany, 79106
      • GSK Investigational Site
  • Bayern
    • Erlangen, Bayern, Germany, 91054
      • GSK Investigational Site
    • Muenchen, Bayern, Germany, 80331
      • GSK Investigational Site
    • Muenchen, Bayern, Germany, 80801
      • GSK Investigational Site
    • Muenchen, Bayern, Germany, 81371
      • GSK Investigational Site
  • Nordrhein-Westfalen
    • Bochum, Nordrhein-Westfalen, Germany, 44791
      • GSK Investigational Site
    • Essen, Nordrhein-Westfalen, Germany, 45122
      • GSK Investigational Site
• Spain
  • Badalona, Spain, 08916
    • GSK Investigational Site
  • Barcelona, Spain, 08036
    • GSK Investigational Site
  • Barcelona, Spain, 08907
    • GSK Investigational Site
  • Madrid, Spain, 28041
    • GSK Investigational Site
  • Madrid, Spain, 28034
    • GSK Investigational Site
  • Móstoles, Madrid, Spain, 28935
    • GSK Investigational Site
  • Valencia, Spain, 46014
    • GSK Investigational Site
• United States
  • California
    • Bakersfield, California, United States, 93301
      • GSK Investigational Site
    • Long Beach, California, United States, 90813
      • GSK Investigational Site
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • GSK Investigational Site
  • Florida
    • Fort Lauderdale, Florida, United States, 33308
      • GSK Investigational Site
    • Jacksonville, Florida, United States, 32216
      • GSK Investigational Site
    • Orlando, Florida, United States, 32804
      • GSK Investigational Site
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • GSK Investigational Site
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • GSK Investigational Site
    • Newark, New Jersey, United States, 07102
      • GSK Investigational Site
    • Somers Point, New Jersey, United States, 08244
      • GSK Investigational Site
  • Ohio
    • Columbus, Ohio, United States, 43210
      • GSK Investigational Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • GSK Investigational Site
    • Philadelphia, Pennsylvania, United States, 19104
      • GSK Investigational Site
  • Tennessee
    • Johnson City, Tennessee, United States, 37604
      • GSK Investigational Site
  • Texas
    • Dallas, Texas, United States, 75246
      • GSK Investigational Site
  • Virginia
    • Annandale, Virginia, United States, 22003
      • GSK Investigational Site
  • Washington
    • Seattle, Washington, United States, 98122-4299
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 18-55 years at the time of first vaccination.
• Known to be HIV-1 infected and under the care of an HIV physician for a minimum of 6 months. However, subjects who initially presented with a clinical diagnosis of primary HIV infection need to have been diagnosed and under care for at least 12 months.
• ART-naïve. Individuals must never have received ART after HIV diagnosis, including lamivudine used for chronic hepatitis B infection, with the exception of short-term ART for prevention of mother-to-child transmission (PMTCT) at least 12 months prior to enrollment.
• Commencement of ART is not expected, based on current assessment, within the next 12 months.
• Viral load level of 2,000-80,000 copies/mL at screening.
• CD4 count >= 500 cells per 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 screening and before vaccination. If ANY exclusion criterion applies, the subject must not be included in the study:

• Infection with HIV-2. This includes patients with dual infection with HIV-1/HIV-2.
• Had an Acquired Immune Deficiency Syndrome (AIDS) defining clinical illness.
• Use of any investigational or non-registered product within 4 weeks preceding the first dose of study vaccine/placebo, or planned use of any investigational or non-registered product other than the study vaccine during the study period.
• Drug therapy with immunomodulators or steroids within the 12 weeks preceding the first dose of study vaccine/placebo or planned administration during the study period. Acute use of steroids up to 4 weeks preceding the first dose for treatment of hypersensitivity reactions is not an exclusion criterion. Inhaled and topical steroids are allowed.
• Administration of immunoglobulins and/ or any blood products within the 12 weeks preceding the first dose of study vaccine/placebo or planned administration during the study period.

• Planned administration of a vaccine not foreseen by the study protocol during

  • the period starting 2 weeks before the first dose of study vaccine/placebo and ending at Visit 3 (Week 6) (after blood sampling),
  • the period starting from 2 weeks prior to Visit 5 (Week 28) and ending at Visit 6 (Week 30) (after blood sampling)
  • the period starting from 2 weeks prior to Visit 8 (Week 48) and ending at Visit 8 (Week 48) (after blood sampling), with the exception of non-adjuvanted influenza vaccine.
• Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product.
• Any previous vaccination or immunotherapy against HIV.
• A family history of hereditary immunodeficiency.
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
• Acute or chronic infective hepatitis.
• Acute or chronic, clinically relevant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination and/or medical history at screening.
• Grade 3 or grade 4 laboratory abnormality, as defined by Division od AIDS (DAIDS) grading table, at screening
• Pregnant or lactating female.
• Any condition which, in the opinion of the investigator, could compromise the subject's safety or adherence to the study protocol.
• History of medically confirmed autoimmune disease.
• History of malignancy, other than squamous cell or basal cell skin cancer, unless there has been surgical excision that is considered to have achieved cure.
• Unstable asthma
• Food or wine induced asthma.
• Known sensitivity to sulfites or aspirin.
• Known sensitivity to aminoglycoside antibiotics.
• Contraindication to intramuscular injection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 3D_HIV Group; HIV-1 infected male and female subjects, between and including 18 to 55 years of age at the time of first vaccination, who received 3 doses of the HIV Vaccine 732462 at Weeks 0, 4 and 28, administered intramuscularly in the deltoid of the non-dominant arm.	Biological: GSK Biologicals HIV Vaccine 732462; 2 or 3 doses according to protocol schedule
EXPERIMENTAL: 2D_HIV Group; HIV-1 infected male and female subjects, between and including 18 to 55 years of age at the time of first vaccination, who received 2 doses of the HIV Vaccine 732462 at Weeks 0 and 4 and one dose of placebo (saline solution) at Week 28, administered intramuscularly in the deltoid of the non-dominant arm.	Biological: GSK Biologicals HIV Vaccine 732462; 2 or 3 doses according to protocol schedule; Drug: Placebo; 1 or 3 doses according to protocol schedule
PLACEBO_COMPARATOR: Control Group; HIV-1 infected male and female subjects, between and including 18 to 55 years of age at the time of first vaccination, who received 3 doses of placebo (saline solution) at Weeks 0, 4 and 28, administered intramuscularly in the deltoid of the non-dominant arm.	Drug: Placebo; 1 or 3 doses according to protocol schedule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Change in Human Immunodeficiency Virus Type 1 (HIV-1) Viral Load (VL) From Baseline	Changes from baseline in HIV-1 viral load (ratio of each value over baseline value) were obtained using crude values and expressed in RNA copies/milliliter [copies/mL]. Baseline of HIV-1 viral load was defined as geometric mean of values measured in blood samples taken at Screening and at Week 0. The HIV type 1, represents the more aggressive virus form, largely responsible for the AIDS pandemic.	At Week 48, post-Dose 3
Geometric Mean Change in HIV-1 VL From Baseline	Changes from baseline in HIV-1 viral load (difference of each value minus baseline value) were obtained using log10-transformed values and expressed in log10-RNA copies/mL. Baseline of HIV-1 viral load was defined as geometric mean of values measured in blood samples taken at Screening and at Week 0. The HIV type 1, represents the more aggressive virus form, largely responsible for the AIDS pandemic.	At Week 48, post-Dose 3
Number of Subjects With Solicited Local Symptoms	Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of symptom regardless of intensity. Grade 3 Pain = pain that prevented normal every day activities. Grade 3 Redness/Swelling = redness or swelling associated with ulceration or secondary infection/phlebitis/sterile abscess/drainage. Medically attended (MA) Pain = pain causing inability to perform basic self-care function or Hospitalization indicated for management of pain. Medically attended Redness/Swelling = redness or swelling associated with necrosis.	During the 7-day (Days 0-6) period following Dose 1
Number of Subjects With Solicited Local Symptoms	Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of symptom regardless of intensity. Grade 3 Pain = pain that prevented normal every day activities. Grade 3 Redness/Swelling = redness or swelling associated with ulceration or secondary infection/phlebitis/sterile abscess/drainage. Medically attended (MA) Pain = pain causing inability to perform basic self-care function or Hospitalization indicated for management of pain. Medically attended Redness/Swelling = redness or swelling associated with necrosis.	During the 7-day (Days 0-6) period following Dose 2
Number of Subjects With Solicited Local Symptoms	Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of symptom regardless of intensity. Grade 3 Pain = pain that prevented normal every day activities. Grade 3 Redness/Swelling = redness or swelling associated with ulceration or secondary infection/phlebitis/sterile abscess/drainage. Medically attended (MA) Pain = pain causing inability to perform basic self-care function or Hospitalization indicated for management of pain. Medically attended Redness/Swelling = redness or swelling associated with necrosis.	During the 7-day (Days 0-6) period following Dose 3
Number of Subjects With Solicited Local Symptoms	Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of symptom regardless of intensity. Grade 3 Pain = pain that prevented normal every day activities. Grade 3 Redness/Swelling = redness or swelling associated with ulceration or secondary infection/phlebitis/sterile abscess/drainage. Medically attended (MA) Pain = pain causing inability to perform basic self-care function or Hospitalization indicated for management of pain. Medically attended Redness/Swelling = redness or swelling associated with necrosis.	During the 7-day (Days 0-6) post-vaccination period, across doses
Number of Subjects With Solicited General Symptoms	Assessed solicited general symptoms(smt.)were abdominalpain,anorexia,diarrhoea,fatigue,headache,myalgia,nausea,sweating,temperature(Temp.)orally=temp.37.7degreesCelsius(°C)&vomiting.Any=occurrene of smt.regardless of intensity.Grade3(G3)Abdominal pain/fatigue/myalgia/sweating/headache=symp.causing inability to perform usual social&functional activities.Medicallyattended(MA)Abdominalpain/fatigue/myalgia/sweating/headache=smt.causing inability to perform basic self-care activities.G3Anorexia=loss of appetite associated with significant weight loss.MAanorexia=aggressive intervention indicated.G3diarrhoea=blood/increased≥7stools per24hours(h)/4fluid replacement.G3nausea=persistent nausea resulting in minimal oral intake for more than48h/with aggressive rehydration indicated.G3vomiting=persistent vomiting resulting in orthostatic hypotension/aggressive.MAdiarrhoea/nausea/vomiting=smt.with life threatening consequences.Related=smt.assessed by the investigator as being related to vaccination	During the 7-day (Days 0-6) period following Dose 1
Number of Subjects With Solicited General Symptoms	Assessed solicited general symptoms(smt.)were abdominalpain,anorexia,diarrhoea,fatigue,headache,myalgia,nausea,sweating,temperature(Temp.)orally=temp.37.7degreesCelsius(°C)&vomiting.Any=occurrene of smt.regardless of intensity.Grade3(G3)Abdominal pain/fatigue/myalgia/sweating/headache=symp.causing inability to perform usual social&functional activities.Medicallyattended(MA)Abdominalpain/fatigue/myalgia/sweating/headache=smt.causing inability to perform basic self-care activities.G3Anorexia=loss of appetite associated with significant weight loss.MAanorexia=aggressive intervention indicated.G3diarrhoea=blood/increased≥7stools per24hours(h)/4fluid replacement.G3nausea=persistent nausea resulting in minimal oral intake for more than48h/with aggressive rehydration indicated.G3vomiting=persistent vomiting resulting in orthostatic hypotension/aggressive.MAdiarrhoea/nausea/vomiting=smt.with life threatening consequences.Related=smt.assessed by the investigator as being related to vaccination	During the 7-day (Days 0-6) period following Dose 2
Number of Subjects With Solicited General Symptoms	Assessed solicited general symptoms(smt.)were abdominalpain,anorexia,diarrhoea,fatigue,headache,myalgia,nausea,sweating,temperature(Temp.)orally=temp.37.7degreesCelsius(°C)&vomiting.Any=occurrene of smt.regardless of intensity.Grade3(G3)Abdominal pain/fatigue/myalgia/sweating/headache=symp.causing inability to perform usual social&functional activities.Medicallyattended(MA)Abdominalpain/fatigue/myalgia/sweating/headache=smt.causing inability to perform basic self-care activities.G3Anorexia=loss of appetite associated with significant weight loss.MAanorexia=aggressive intervention indicated.G3diarrhoea=blood/increased≥7stools per24hours(h)/4fluid replacement.G3nausea=persistent nausea resulting in minimal oral intake for more than48h/with aggressive rehydration indicated.G3vomiting=persistent vomiting resulting in orthostatic hypotension/aggressive.MAdiarrhoea/nausea/vomiting=smt.with life threatening consequences.Related=smt.assessed by the investigator as being related to vaccination	During the 7-day (Days 0-6) period following Dose 3
Number of Subjects With Solicited General Symptoms	Assessed solicited general symptoms(smt.)were abdominalpain,anorexia,diarrhoea,fatigue,headache,myalgia,nausea,sweating,temperature(Temp.)orally=temp.37.7degreesCelsius(°C)&vomiting.Any=occurrene of smt.regardless of intensity.Grade3(G3)Abdominal pain/fatigue/myalgia/sweating/headache=symp.causing inability to perform usual social&functional activities.Medicallyattended(MA)Abdominalpain/fatigue/myalgia/sweating/headache=smt.causing inability to perform basic self-care activities.G3Anorexia=loss of appetite associated with significant weight loss.MAanorexia=aggressive intervention indicated.G3diarrhoea=blood/increased≥7stools per24hours(h)/4fluid replacement.G3nausea=persistent nausea resulting in minimal oral intake for more than48h/with aggressive rehydration indicated.G3vomiting=persistent vomiting resulting in orthostatic hypotension/aggressive.MAdiarrhoea/nausea/vomiting=smt.with life threatening consequences.Related=smt.assessed by the investigator as being related to vaccination	During the 7-day (Days 0-6) post-vaccination period, across doses
Number of Subjects With Unsolicited Adverse Events (AEs)	An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 (G3) AE = an AE which prevented normal, everyday activities. Related = AE assessed by the investigator as related to the vaccination. Unsolicited AEs were tabulated following Dose 1 and Dose 2 vaccinations.	During the 28-Day (Days 0-27) period following Dose 1 and Dose 2
Number of Subjects With Unsolicited AEs	An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 (G3) AE = an AE which prevented normal, everyday activities. Related = AE assessed by the investigator as related to the vaccination. Unsolicited AEs were tabulated following Dose 3 and across doses.	During the 28-Day (Days 0-27) post-vaccination period
Number of Subjects With Serious Adverse Events (SAEs)	Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.	During the entire study period (up to Week 48)
Number of Subjects With Potentially Immune-Mediated Diseases (pIMDs)	Potentially Immune-Mediated Diseases (pIMDs) are a subset of AEs that include both clearly autoimmune diseases and also other inflammatory and/or neurologic disorders which may or may not have an autoimmune etiology.	During the entire study period (up to Week 48)
Number of Subjects With Abnormal Haematological and Biochemical Values	Among the biochemical and haematological parameters with abnormal values were alanine aminotransferase [ALT], albumin [ALB], alkaline phosphatase [ALP], aspartate aminotransferase [AST], bilirubin (total) [BIL], creatinine [CRE], eosinophils [EOS], eosinophils/100 leukocytes [EOS/100LEU], bicarbonate [BIC], haemoglobin [HGB], potassium [PTS], lymphocytes [LYM], lymphocytes/100 leukocytes [LYM/100LEU], sodium [SDI], neutrophils [NEU], neutrophils/100 leukocytes [NEU/100LEU], platelet count [PLC], prothrombin time-international normalized ratio [PTT] and white blood cell count [WBC]. Assessed grades (G) for laboratory parameters were 0, 1 (mild), 2 (moderate), 3 (severe) and 4 (potentially life-threatening), according to DAIDS (division of AIDS table for grading the severity of adult and pediatric adverse events -Version 1.0).	At Screening
Number of Subjects With Abnormal Haematological and Biochemical Values	Among the biochemical and haematological parameters with abnormal values were alanine aminotransferase [ALT], albumin [ALB], alkaline phosphatase [ALP], aspartate aminotransferase [AST], bilirubin (total) [BIL], creatinine [CRE], eosinophils [EOS], eosinophils/100 leukocytes [EOS/100LEU], bicarbonate [BIC], haemoglobin [HGB], potassium [PTS], lymphocytes [LYM], lymphocytes/100 leukocytes [LYM/100LEU], sodium [SDI], neutrophils [NEU], neutrophils/100 leukocytes [NEU/100LEU], platelet count [PLC], prothrombin time-international normalized ratio [PTT] and white blood cell count [WBC]. Assessed grades (G) for laboratory parameters were 0, 1 (mild), 2 (moderate), 3 (severe) and 4 (potentially life-threatening), according to DAIDS (division of AIDS table for grading the severity of adult and pediatric adverse events -Version 1.0).	Pre-vaccination, at Week 0
Number of Subjects With Abnormal Haematological and Biochemical Values	Among the biochemical and haematological parameters with abnormal values were alanine aminotransferase [ALT], albumin [ALB], alkaline phosphatase [ALP], aspartate aminotransferase [AST], bilirubin (total) [BIL], creatinine [CRE], eosinophils [EOS], eosinophils/100 leukocytes [EOS/100LEU], bicarbonate [BIC], haemoglobin [HGB], potassium [PTS], lymphocytes [LYM], lymphocytes/100 leukocytes [LYM/100LEU], sodium [SDI], neutrophils [NEU], neutrophils/100 leukocytes [NEU/100LEU], platelet count [PLC], prothrombin time-international normalized ratio [PTT] and white blood cell count [WBC]. Assessed grades (G) for laboratory parameters were 0, 1 (mild), 2 (moderate), 3 (severe) and 4 (potentially life-threatening), according to DAIDS (division of AIDS table for grading the severity of adult and pediatric adverse events -Version 1.0).	At Week 4
Number of Subjects With Abnormal Haematological and Biochemical Values	Among the biochemical and haematological parameters with abnormal values were alanine aminotransferase [ALT], albumin [ALB], alkaline phosphatase [ALP], aspartate aminotransferase [AST], bilirubin (total) [BIL], creatinine [CRE], eosinophils [EOS], eosinophils/100 leukocytes [EOS/100LEU], bicarbonate [BIC], haemoglobin [HGB], potassium [PTS], lymphocytes [LYM], lymphocytes/100 leukocytes [LYM/100LEU], sodium [SDI], neutrophils [NEU], neutrophils/100 leukocytes [NEU/100LEU], platelet count [PLC], prothrombin time-international normalized ratio [PTT] and white blood cell count [WBC]. Assessed grades (G) for laboratory parameters were 0, 1 (mild), 2 (moderate), 3 (severe) and 4 (potentially life-threatening), according to DAIDS (division of AIDS table for grading the severity of adult and pediatric adverse events -Version 1.0).	At Week 6
Number of Subjects With Abnormal Haematological and Biochemical Values	Among the biochemical and haematological parameters with abnormal values were alanine aminotransferase [ALT], albumin [ALB], alkaline phosphatase [ALP], aspartate aminotransferase [AST], bilirubin (total) [BIL], creatinine [CRE], eosinophils [EOS], eosinophils/100 leukocytes [EOS/100LEU], bicarbonate [BIC], haemoglobin [HGB], potassium [PTS], lymphocytes [LYM], lymphocytes/100 leukocytes [LYM/100LEU], sodium [SDI], neutrophils [NEU], neutrophils/100 leukocytes [NEU/100LEU], platelet count [PLC], prothrombin time-international normalized ratio [PTT] and white blood cell count [WBC]. Assessed grades (G) for laboratory parameters were 0, 1 (mild), 2 (moderate), 3 (severe) and 4 (potentially life-threatening), according to DAIDS (division of AIDS table for grading the severity of adult and pediatric adverse events -Version 1.0).	At Week 16
Number of Subjects With Abnormal Haematological and Biochemical Values	Among the biochemical and haematological parameters with abnormal values were alanine aminotransferase [ALT], albumin [ALB], alkaline phosphatase [ALP], aspartate aminotransferase [AST], bilirubin (total) [BIL], creatinine [CRE], eosinophils [EOS], eosinophils/100 leukocytes [EOS/100LEU], bicarbonate [BIC], haemoglobin [HGB], potassium [PTS], lymphocytes [LYM], lymphocytes/100 leukocytes [LYM/100LEU], sodium [SDI], neutrophils [NEU], neutrophils/100 leukocytes [NEU/100LEU], platelet count [PLC], prothrombin time-international normalized ratio [PTT] and white blood cell count [WBC]. Assessed grades (G) for laboratory parameters were 0, 1 (mild), 2 (moderate), 3 (severe) and 4 (potentially life-threatening), according to DAIDS (division of AIDS table for grading the severity of adult and pediatric adverse events -Version 1.0).	At Week 28
Number of Subjects With Abnormal Haematological and Biochemical Values	Among the biochemical and haematological parameters with abnormal values were alanine aminotransferase [ALT], albumin [ALB], alkaline phosphatase [ALP], aspartate aminotransferase [AST], bilirubin (total) [BIL], creatinine [CRE], eosinophils [EOS], eosinophils/100 leukocytes [EOS/100LEU], bicarbonate [BIC], haemoglobin [HGB], potassium [PTS], lymphocytes [LYM], lymphocytes/100 leukocytes [LYM/100LEU], sodium [SDI], neutrophils [NEU], neutrophils/100 leukocytes [NEU/100LEU], platelet count [PLC], prothrombin time-international normalized ratio [PTT] and white blood cell count [WBC]. Assessed grades (G) for laboratory parameters were 0, 1 (mild), 2 (moderate), 3 (severe) and 4 (potentially life-threatening), according to DAIDS (division of AIDS table for grading the severity of adult and pediatric adverse events -Version 1.0).	At Week 30
Number of Subjects With Abnormal Haematological and Biochemical Values	Among the biochemical and haematological parameters with abnormal values were alanine aminotransferase [ALT], albumin [ALB], alkaline phosphatase [ALP], aspartate aminotransferase [AST], bilirubin (total) [BIL], creatinine [CRE], eosinophils [EOS], eosinophils/100 leukocytes [EOS/100LEU], bicarbonate [BIC], haemoglobin [HGB], potassium [PTS], lymphocytes [LYM], lymphocytes/100 leukocytes [LYM/100LEU], sodium [SDI], neutrophils [NEU], neutrophils/100 leukocytes [NEU/100LEU], platelet count [PLC], prothrombin time-international normalized ratio [PTT] and white blood cell count [WBC]. Assessed grades (G) for laboratory parameters were 0, 1 (mild), 2 (moderate), 3 (severe) and 4 (potentially life-threatening), according to DAIDS (division of AIDS table for grading the severity of adult and pediatric adverse events -Version 1.0).	At Week 38
Number of Subjects With Abnormal Haematological and Biochemical Values	Among the biochemical and haematological parameters with abnormal values were alanine aminotransferase [ALT], albumin [ALB], alkaline phosphatase [ALP], aspartate aminotransferase [AST], bilirubin (total) [BIL], creatinine [CRE], eosinophils [EOS], eosinophils/100 leukocytes [EOS/100LEU], bicarbonate [BIC], haemoglobin [HGB], potassium [PTS], lymphocytes [LYM], lymphocytes/100 leukocytes [LYM/100LEU], sodium [SDI], neutrophils [NEU], neutrophils/100 leukocytes [NEU/100LEU], platelet count [PLC], prothrombin time-international normalized ratio [PTT] and white blood cell count [WBC]. Assessed grades (G) for laboratory parameters were 0, 1 (mild), 2 (moderate), 3 (severe) and 4 (potentially life-threatening), according to DAIDS (division of AIDS table for grading the severity of adult and pediatric adverse events -Version 1.0).	At Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Change in HIV-1 Viral Load (LV) From Baseline	Changes from baseline in HIV-1 viral load (ratio of each value over baseline value) were obtained using crude values and expressed in RNA copies/mL. Baseline of HIV-1 viral load was defined as the geometric mean of values measured in blood samples taken at Screening and at Week 0. The HIV type 1, represents the more aggressive virus form, largely responsible for the AIDS pandemic. Changes from baseline were measured at Week 1 to 28 for the HIV Group, Weeks 30 and 38 for the 3D_HIV Group and 2D_HIV Group and from Week 1 to Week 38 for the Control Group.	At Weeks 1, 4, 6, 16, 28, 30 and 38
Geometric Mean Change in HIV-1 VL From Baseline	Changes from baseline in HIV-1 viral load (difference of each value minus baseline value) were obtained using log10-transformed values and expressed in log10-RNA copies/mL. Baseline of HIV-1 viral load was defined as geometric mean of values measured in blood samples taken at Screening and at Week 0. The HIV type 1, represents the more aggressive virus form, largely responsible for the AIDS pandemic. Changes from baseline were measured at Week 1 to 29 for the HIV Group, Weeks 30 and 38 for the 3D_HIV Group and 2D_HIV Group and from Week 1 to Week 38 for the Control Group.	At Weeks 1, 4, 6, 16, 28, 30 and 38
Levels of HIV-1 Viral Load (VL)	HIV-1 VL, using crude values, was expressed in RNA copies/mL and measured from Screening to Week 28 for the HIV Group, Weeks 30, 38 and 48 for the 3D_HIV Group and 2D_HIV Group and from Screening to Week 48 for the Control Group.	At Screening, Pre-vaccination and at Weeks 1, 4, 6, 16, 28, 30, 38 and 48
Levels of HIV-1 VL	HIV-1 VL, using log10 transformed values, was expressed in log10-RNA copies/mL and measured from Screening to Week 28 for the HIV Group, Weeks 30, 38 and 48 for the 3D_HIV Group and 2D_HIV Group and from Screening to Week 48 for the Control Group.	At Screening, Pre-vaccination and at Weeks 1, 4, 6, 16, 28, 30, 38 and 48
Percentage of Subjects With Plasmatic HIV-1 Viral Load Decrease Higher Than (>) 1	The proportion of subjects with >1 decrease of HIV-1 VL, was determined using log10-transformed values.	At Week 48
Cluster of Differentiation 4 (CD4) Absolute Cell Count	Result determination, using crude values, was done from Screening to Week 28 for the HIV Group, Weeks 30, 38 and 48 for the 3D_HIV Group and 2D_HIV Group and from Screening (SCR) to Week (W) 48 for the Control Group.	At Screening, Pre-vaccination and at Weeks 1, 4, 6, 16, 28, 30, 38 and 48
Mean Change in CD4 Cell Count From Baseline	Baseline for CD4 cell count analysis was defined as the mean of values measured in blood taken at Screening and at pre vaccination (PRE). Result determination, using crude values, was done from week 1 to 28 for the HIV Group, weeks 30, 38 and 48 for the 3D_HIV Group and 2D_HIV Group and from week 1 to week 48 for the Control Group.	At Weeks 1, 4, 6, 16, 28, 30, 38 and 48
Percentage of Subjects With ART (Anti-Retroviral Therapy) Initiation and HIV-related Clinical Events	Only actual ART initiations were reported under the category "ART initiation". HIV-related clinical events were defined as: clinical disease progression, or confirmed VL > 100.000 copies/mL, or confirmed CD4 cell count < 350 cells/ cubic millimeter (mm3).	During the entire study period (up to Week 48)
Magnitude of Antigen Specific Cluster of Differentiation-40 Ligand (CD40L)+CD4+ T-cells Expressing at Least Interleukin-2 (IL-2)	Magnitude was defined as the frequency of proteins 17, 24, Nef, reverse transcriptase (RT) - specific CD40L+CD4+ T-cells and F4co-Computed [frequency of CD4+ T-cells expressing markers in the response to the F4co fusion protein was estimated by adding individual frequencies of CD4+ T-cells to each of the 4 antigens (Nef, p17, p24, RT)] CD40L+CD4+ T-cells expressing at least interleukin- 2 (IL-2), as assessed by Intracellular Cytokine Staining (ICS).	During the entire study period - up to Week 48 (Pre-vaccination, Weeks 6, 28, 30 and 48 for the 3D_HIV Group, 2D_HIV Group and Control Group and at Pre-vaccination, Weeks 6 and 28 for the HIV Group)
Magnitude of Antigen Specific CD40L+CD4+ T-cells Expressing at Least One Cytokine	Magnitude was defined as the frequency of proteins 17, 24, Nef, reverse transcriptase (RT) - specific CD40L+CD4+ T-cells and F4co-Computed [frequency of CD4+ T-cells expressing markers in the response to the F4co fusion protein was estimated by adding individual frequencies of CD4+ T-cells to each of the 4 antigens (Nef, p17, p24, RT)] CD40L+CD4+ T-cells expressing at least interleukin- 2 (IL-2) or another cytokine among interferon-gamma (IFN-γ) and/or tumour necrosis-alpha (TNF-α), as assessed by Intracellular Cytokine Staining (ICS).	During the entire study period - up to Week 48 (Pre-vaccination, Weeks 6, 28, 30 and 48 for the 3D_HIV Group, 2D_HIV Group and Control Group and at Pre-vaccination, Weeks 6 and 28 for the HIV Group)
Magnitude of Antigen Specific CD40L-CD4+ T-cells Expressing at Least One Cytokine.	Magnitude was defined as the frequency of proteins 17, 24, Nef, reverse transcriptase (RT) - specific CD40L-CD4+ T-cells and F4co-Computed [frequency of CD4+ T-cells expressing markers in the response to the F4co fusion protein was estimated by adding individual frequencies of CD4+ T-cells to each of the 4 antigens (Nef, p17, p24, RT)] CD40L-CD4+ T-cells expressing at least interleukin- 2 (IL-2) or another cytokine among interferon-gamma (IFN-γ) and/or tumour necrosis-alpha (TNF-α), as assessed by Intracellular Cytokine Staining (ICS).	During the entire study period - up to Week 48 (Pre-vaccination, Weeks 6, 28, 30 and 48 for the 3D_HIV Group, 2D_HIV Group and Control Group and at Pre-vaccination, Weeks 6 and 28 for the HIV Group)
Magnitude of Antigen Specific CD4+ T-cells Expressing at Least One Cytokine	Magnitude was defined as the frequency of proteins 17, 24, Nef, reverse transcriptase (RT) - specific CD4+ T-cells and F4co-Computed [frequency of CD4+ T-cells expressing markers in the response to the F4co fusion protein was estimated by adding individual frequencies of CD4+ T-cells to each of the 4 antigens (Nef, p17, p24, RT)] CD4+ T-cells expressing at least interleukin- 2 (IL-2) or another cytokine among interferon-gamma (IFN-γ) and/or tumour necrosis-alpha (TNF-α), as assessed by Intracellular Cytokine Staining (ICS).	During the entire study period - up to Week 48 (Pre-vaccination, Weeks 6, 28, 30 and 48 for the 3D_HIV Group, 2D_HIV Group and Control Group and at Pre-vaccination, Weeks 6 and 28 for the HIV Group)
Magnitude of Antigen Specific CD8+ T-cells Expressing at Least One Cytokine	Magnitude was defined as the frequency of proteins 17, 24, Nef, reverse transcriptase (RT) - specific CD8+ T-cells and F4co-Computed [frequency of CD8+ T-cells expressing markers in the response to the F4co fusion protein was estimated by adding individual frequencies of CD8+ T-cells to each of the 4 antigens (Nef, p17, p24, RT)] CD8+ T-cells expressing at least interleukin- 2 (IL-2) or another cytokine among interferon-gamma (IFN-γ) and/or tumour necrosis-alpha (TNF-α), as assessed by Intracellular Cytokine Staining (ICS).	During the entire study period - up to Week 48 (Pre-vaccination, Weeks 6, 28, 30 and 48 for the 3D_HIV Group, 2D_HIV Group and Control Group and at Pre-vaccination, Weeks 6 and 28 for the HIV Group)
Number of Subjects With Response to at Least 1, 2, 3 or 4 Antigens	Breadth was assessed only for the CD4+ T-cells and was measured by evaluating response to at least 1, 2, 3 or all 4 antigens: proteins 17, 24, Nef, reverse transcriptase (RT).	During the entire study period - up to Week 48 (Pre-vaccination, Weeks 6, 28, 30 and 48 for the 3D_HIV Group, 2D_HIV Group and Control Group and at Pre-vaccination, Weeks 6 and 28 for the HIV Group)
Cytokine Expression Profile of F4co-Computed CD4+ T Cells	The cytokine co-expression profile was defined by the frequency of F4co-Computed CD4+ T-cells [frequency of CD4+ T-cells expressing markers in the response to the F4co fusion protein was estimated by adding individual frequencies of CD4+ T-cells to each of the 4 antigens (Nef, p17, p24, RT)] expressing CD40L and/or IL-2 and/or tumour necrosis factor-alpha (TNF-α) and/or interferon-gamma (IFN-γ).	During the entire study period - up to Week 48 (Pre-vaccination, Weeks 6, 28, 30 and 48 for the 3D_HIV Group, 2D_HIV Group and Control Group and at Pre-vaccination, Weeks 6 and 28 for the HIV Group)
Cytokine Expression Profile of Nef Antigen-specific CD4+ T-cells	The cytokine co-expression profile was defined by the frequency of Nef-specific CD4+ T-cells expressing CD40L and/or IL-2 and/or tumour necrosis factor-alpha (TNF-α) and/or interferon-gamma (IFN-γ).	During the entire study period - up to Week 48 (Pre-vaccination, Weeks 6, 28, 30 and 48 for the 3D_HIV Group, 2D_HIV Group and Control Group and at Pre-vaccination, Weeks 6 and 28 for the HIV Group)
Cytokine Expression Profile of P17 Antigen-specific CD4+ T-cells	The cytokine co-expression profile was defined by the frequency of P17-specific CD4+ T-cells expressing CD40L and/or IL-2 and/or tumour necrosis factor-alpha (TNF-α) and/or interferon-gamma (IFN-γ).	During the entire study period - up to Week 48 (Pre-vaccination, Weeks 6, 28, 30 and 48 for the 3D_HIV Group, 2D_HIV Group and Control Group and at Pre-vaccination, Weeks 6 and 28 for the HIV Group)
Cytokine Expression Profile of P24 Antigen-specific CD4+ T-cells	The cytokine co-expression profile was defined by the frequency of P24-specific CD4+ T-cells expressing CD40L and/or IL-2 and/or tumour necrosis factor-alpha (TNF-α) and/or interferon-gamma (IFN-γ).	During the entire study period - up to Week 48 (Pre-vaccination, Weeks 6, 28, 30 and 48 for the 3D_HIV Group, 2D_HIV Group and Control Group and at Pre-vaccination, Weeks 6 and 28 for the HIV Group)
Cytokine Expression Profile of RT Antigen-specific CD4+ T-cells	The cytokine co-expression profile was defined by the frequency of reverse transcriptase (RT)-specific CD4+ T-cells expressing CD40L and/or IL-2 and/or tumour necrosis factor-alpha (TNF-α) and/or interferon-gamma (IFN-γ).	During the entire study period - up to Week 48 (Pre-vaccination, Weeks 6, 28, 30 and 48 for the 3D_HIV Group, 2D_HIV Group and Control Group and at Pre-vaccination, Weeks 6 and 28 for the HIV Group)
Cytokine Expression Profile of F4co-Computed CD8+ T Cells	The cytokine co-expression profile was defined by the frequency of F4co-Computed CD8+ T-cells [Frequency of CD8+ T cells expressing markers in the response to the F4co fusion protein was estimated by adding individual frequencies of CD8+ T-cells to each of the 4 antigens (Nef, p17, p24, RT)] expressing CD40L and/or IL-2 and/or TNF-α and/or IFN-γ.	During the entire study period - up to Week 48 (Pre-vaccination, Weeks 6, 28, 30 and 48 for the 3D_HIV Group, 2D_HIV Group and Control Group and at Pre-vaccination, Weeks 6 and 28 for the HIV Group)
Cytokine Expression Profile of Nef Antigen-specific CD8+ T-cells	The cytokine co-expression profile was defined by the frequency of Nef-specific CD8+ T-cells expressing CD40L and/or IL-2 and/or TNF-α and/or IFN-γ.	During the entire study period - up to Week 48 (Pre-vaccination, Weeks 6, 28, 30 and 48 for the 3D_HIV Group, 2D_HIV Group and Control Group and at Pre-vaccination, Weeks 6 and 28 for the HIV Group)
Cytokine Expression Profile of P17 Antigen-specific CD8+ T-cells	The cytokine co-expression profile was defined by the frequency of P17-specific CD8+ T-cells expressing CD40L and/or IL-2 and/or TNF-α and/or IFN-γ.	During the entire study period - up to Week 48 (Pre-vaccination, Weeks 6, 28, 30 and 48 for the 3D_HIV Group, 2D_HIV Group and Control Group and at Pre-vaccination, Weeks 6 and 28 for the HIV Group)
Cytokine Expression Profile of P24 Antigen-specific CD8+ T-cells	The cytokine co-expression profile was defined by the frequency of P24-specific CD8+ T-cells expressing CD40L and/or IL-2 and/or TNF-α and/or IFN-γ.	During the entire study period - up to Week 48 (Pre-vaccination, Weeks 6, 28, 30 and 48 for the 3D_HIV Group, 2D_HIV Group and Control Group and at Pre-vaccination, Weeks 6 and 28 for the HIV Group)
Cytokine Expression Profile of RT Antigen-specific CD8+ T-cells	The cytokine co-expression profile was defined by the frequency of reverse transcriptase (RT)-specific CD8+ T-cells expressing CD40L and/or IL-2 and/or TNF-α and/or IFN-γ.	During the entire study period - up to Week 48 (Pre-vaccination, Weeks 6, 28, 30 and 48 for the 3D_HIV Group, 2D_HIV Group and Control Group and at Pre-vaccination, Weeks 6 and 28 for the HIV Group)
Number of Seropositive Subjects for Anti-P17 Antibodies	Seropositivity rates for antibodies against P17 antigen were assessed using the Enzyme-Linked Immunosorbent Assay (ELISA), with a reference cut-off value greater than or equal to (≥) 187 milli-ELISA units per milliliter (mEL.U/mL).	During the entire study period - up to Week 48 (Pre-vaccination, Weeks 6, 28, 30 and 48 for the 3D_HIV Group, 2D_HIV Group and Control Group and at Pre-vaccination, Weeks 6 and 28 for the HIV Group)
Number of Seropositive Subjects for Anti-P24 Antibodies	Seropositivity rates for antibodies against P24 antigen were assessed using the Enzyme-Linked Immunosorbent Assay (ELISA), with a reference cut-off value greater than or equal to (≥) 119 milli-ELISA units per milliliter (mEL.U/mL).	During the entire study period - up to Week 48 (Pre-vaccination, Weeks 6, 28, 30 and 48 for the 3D_HIV Group, 2D_HIV Group and Control Group and at Pre-vaccination, Weeks 6 and 28 for the HIV Group)
Number of Seropositive Subjects for Anti-Nef Antibodies	Seropositivity rates for antibodies against Nef antigen were assessed using the Enzyme-Linked Immunosorbent Assay (ELISA), with a reference cut-off value greater than or equal to (≥) 494 milli-ELISA units per milliliter (mEL.U/mL).	During the entire study period - up to Week 48 (Pre-vaccination, Weeks 6, 28, 30 and 48 for the 3D_HIV Group, 2D_HIV Group and Control Group and at Pre-vaccination, Weeks 6 and 28 for the HIV Group)
Number of Seropositive Subjects for Anti-RT Antibodies	Seropositivity rates for antibodies against RT antigen were assessed using the Enzyme-Linked Immunosorbent Assay (ELISA), with a reference cut-off value greater than or equal to (≥) 125 milli-ELISA units per milliliter (mEL.U/mL).	During the entire study period - up to Week 48 (Pre-vaccination, Weeks 6, 28, 30 and 48 for the 3D_HIV Group, 2D_HIV Group and Control Group and at Pre-vaccination, Weeks 6 and 28 for the HIV Group)
Number of Seropositive Subjects for Anti-F4co Antibodies	Seropositivity rates for antibodies against F4co antigen were assessed using the Enzyme-Linked Immunosorbent Assay (ELISA), with a reference cut-off value greater than or equal to (≥) 42 milli-ELISA units per milliliter (mEL.U/mL).	During the entire study period - up to Week 48 (Pre-vaccination, Weeks 6, 28, 30 and 48 for the 3D_HIV Group, 2D_HIV Group and Control Group and at Pre-vaccination, Weeks 6 and 28 for the HIV Group)

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 8, 2010
• Primary Completion (ACTUAL): November 5, 2012
• Study Completion (ACTUAL): November 5, 2012

Study Registration Dates

• First Submitted: October 7, 2010
• First Submitted That Met QC Criteria: October 7, 2010
• First Posted (ESTIMATE): October 11, 2010

Study Record Updates

• Last Update Posted (ACTUAL): May 21, 2018
• Last Update Submitted That Met QC Criteria: April 19, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: safety; vaccine; immunogenicity; HIV infection; reactogenicity; Human Immunodeficiency Virus (HIV)-1
• Other Study ID Numbers: 111679