A Study to Explore Reconstitution of Immunity in Patients With Advanced HIV-1-infection (RESTORE)

This study has been completed.
Sponsor:
Collaborators:
Chulalongkorn University
HIV Netherlands Australia Thailand Research Collaboration
St Vincent's Hospital, Sydney
Information provided by (Responsible Party):
Kirby Institute
ClinicalTrials.gov Identifier:
NCT01296373
First received: February 13, 2011
Last updated: December 17, 2013
Last verified: December 2013

February 13, 2011
December 17, 2013
September 2010
March 2013   (final data collection date for primary outcome measure)
Longitudnal Changes in CD4+ T-cell with combination antiretoviral therapy [ Time Frame: 2-3 years ] [ Designated as safety issue: No ]
Not Provided
Complete list of historical versions of study NCT01296373 on ClinicalTrials.gov Archive Site
  • Longitudinal changes in T-cell subsets with combination antiretroviral therapy [ Time Frame: 2-3 years ] [ Designated as safety issue: No ]
  • Longitudinal changes in CD4+ T-cell immune responses to common pathogens during combination antiretroviral therapy [ Time Frame: 2-3 years ] [ Designated as safety issue: No ]
Not Provided
Not Provided
Not Provided
 
A Study to Explore Reconstitution of Immunity in Patients With Advanced HIV-1-infection
An Observational Study to Explore Reconstitution of Immunity in Patients With Advanced HIV-1-infection Commencing Combination Antiretroviral Therapy (HIVNAT 136 RESTORE Study:Thailand)

RESTORE study:Thailand is a prospective observational study of HIV-1-infected patients who are either treatment naïve or who have been off anti-retroviral therapy for a ≥12 months, who have a CD4+ T cell count less than or equal to 350 cells/µL and who have been deemed by their treating physician that commencement of combination antiretroviral therapy (cART), which is expected to reduce plasma HIV RNA by ≥1log10 copies/mL, is necessary.

The primary intent of this protocol is to prospectively establish a cohort of patients from whom clinical data and peripheral blood samples (serum, plasma and peripheral blood mononuclear cells) can be stored for substudies examining reconstitution of the immune system and its relationship to disease outcomes.

RESTORE study:Thailand is a prospective observational study of HIV-1-infected patients who are either treatment naïve or who have been off anti-retroviral therapy for a ≥12 months, who have a CD4+ T cell count less than or equal to 350 cells/µL and who have been deemed by their treating physician that commencement of combination antiretroviral therapy (cART) which is expected to reduce plasma HIV RNA by ≥1log10 copies/mL is necessary.

The primary intent of this protocol is to prospectively establish a cohort of patients from whom clinical data and peripheral blood samples (serum, plasma and peripheral blood mononuclear cells) can be stored for substudies examining reconstitution of the immune system and its relationship to disease outcomes.

Patients who have recently had an opportunistic infection (OI) can also be enrolled. Investigators should consider the results of the ACTG A5164 (1), SAPIT (2), and Makadzange and colleagues (3) studies in regard to the timing of cART introduction following the acute OI. This observational protocol does not stipulate the timing of cART introduction, but cART should not normally be delayed beyond 2 months after the diagnosis of an acute OI.

Patients will be commenced on cART regimens as determined by the treating physician. Patients will be observed and pertinent clinical data will be recorded at visits that will coincide with their standard of care visits. The visit schedule in year 1 is as follows: screening/baseline (cART is commenced), week 4, 8, 12, 24 and 48. In year 2 and 3 visits are every 6 months. In those who, in the opinion of the investigator, develop a major clinical manifestation of immune restoration disease (IRD) an extra visit (IRD baseline) will be conducted. If the patient is in the first 12 weeks of study follow-up, this is the only additional visit required. If, however, the major IRD event occurs after the week 12 visit in year 1 or in years 2 and 3, in addition to the IRD baseline visit a second additional visit will be conducted 4 weeks later. It is likely that these extra visits would be required for the management of their clinical disease. Details pertaining to the cause, course and treatment of the IRD event will be recorded. These will include clinical data and pathology results. Prior to starting cART and at each study visit, extra blood samples will be taken for storage and subsequent analysis. It is envisaged that these storage samples will be used for subsequent exploration of aspects of immunity (including but not limited to pathogen specific immune responses including pathogen load; anti-HIV immunity; pathogen specific (and other) clinical syndromes associated with immune reconstitution; B-cell responses); immune activation and HIV viral dynamics. A sample for genetic testing will be obtained at baseline. The rationale for this is to determine host genetic polymorphisms that may predict immune reconstitution with cART and/or predispose to the development of IRD. Patients will be followed for 3 years.

Observational
Observational Model: Cohort
Time Perspective: Prospective
Not Provided
Retention:   Samples With DNA
Description:

serum, plasma, PBMC and DNA will be stored for 10 years total.

Non-Probability Sample

HIV-1-infected adults aged 18 years or older with untreated HIV-1-infection and CD4+ of 350 cells/uL or less who are about to start or recommence combination antiretroviral therapy which is expected to result in a 1 log or greater decline in plasma HIV RNA

HIV Immune Restoration
Not Provided
HIV-1-infected, off ART
HIV-1-infected, antiretroviral naive or off antiretroviral therapy for at least 12 months with CD4+ T-cell counts less than or equal to 350 cells/µL who are about to commence combination antiretroviral therapy
Hsu DC, Kerr SJ, Iampornsin T, Pett SL, Avihingsanon A, Thongpaeng P, Zaunders JJ, Ubolyam S, Ananworanich J, Kelleher AD, Cooper DA. Restoration of CMV-specific-CD4 T cells with ART occurs early and is greater in those with more advanced immunodeficiency. PLoS One. 2013 Oct 10;8(10):e77479. doi: 10.1371/journal.pone.0077479.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
53
September 2013
March 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

. Age ≥18 years;

  • Provision of written, informed consent;
  • Untreated, HIV infected patients with CD4+ T cell counts 350 cells/µL or less;
  • Treatment naïve or off ART for ≥12 months;
  • Intention to commence cART that would be expected to reduce viral load by one log or greater

Exclusion Criteria:

  • Inability to give written informed consent;
  • Any condition which the treating physician feels would compromise the ability of the patient to participate in the study.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Thailand
 
NCT01296373
HIVNAT 136
No
Kirby Institute
Kirby Institute
  • Chulalongkorn University
  • HIV Netherlands Australia Thailand Research Collaboration
  • St Vincent's Hospital, Sydney
Study Director: Sarah L Pett, MD National Centre in HIV Epidemiology and Clinical Research
Study Chair: David A Cooper, MD National Centre in HIV Epidemiology and Clinical Research
Study Chair: Anthony D Kelleher, MD St Vincent's Hospital, Sydney
Principal Investigator: Denise Hsu, MD The HIV Netherlands Australia Thailand Research Collaboration
Principal Investigator: Jintanat Ananworanich, MD The HIV Netherlands Australia Thailand Research Collaboration
Kirby Institute
December 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP