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
  Purpose

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.


Condition
HIV Immune Restoration

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: An Observational Study to Explore Reconstitution of Immunity in Patients With Advanced HIV-1-infection Commencing Combination Antiretroviral Therapy (HIVNAT 136 RESTORE Study:Thailand)

Resource links provided by NLM:


Further study details as provided by Kirby Institute:

Primary Outcome Measures:
  • Longitudnal Changes in CD4+ T-cell with combination antiretoviral therapy [ Time Frame: 2-3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Biospecimen Retention:   Samples With DNA

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


Enrollment: 53
Study Start Date: September 2010
Study Completion Date: September 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts
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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

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

Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01296373

Locations
Thailand
HIV-NAT
Bangkok, Thailand
Sponsors and Collaborators
Kirby Institute
Chulalongkorn University
HIV Netherlands Australia Thailand Research Collaboration
St Vincent's Hospital, Sydney
Investigators
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
  More Information

No publications provided by Kirby Institute

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Kirby Institute
ClinicalTrials.gov Identifier: NCT01296373     History of Changes
Other Study ID Numbers: HIVNAT 136
Study First Received: February 13, 2011
Last Updated: December 17, 2013
Health Authority: Thailand: Ministry of Public Health

Keywords provided by Kirby Institute:
HIV-1
immune
restoration
observational

ClinicalTrials.gov processed this record on September 15, 2014