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

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.

Study Overview

• Status: Completed
• Conditions: HIV Immune Restoration

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.

• Study Type: Observational
• Enrollment (Actual): 53

Contacts and Locations

Study Locations

• Thailand
  • Bangkok, Thailand
    • HIV-NAT

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Longitudnal Changes in CD4+ T-cell with combination antiretoviral therapy	2-3 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Longitudinal changes in T-cell subsets with combination antiretroviral therapy	2-3 years
Longitudinal changes in CD4+ T-cell immune responses to common pathogens during combination antiretroviral therapy	2-3 years

Collaborators and Investigators

• Sponsor: Kirby Institute
• Collaborators: Chulalongkorn University; St Vincent's Hospital, Sydney; HIV Netherlands Australia Thailand Research Collaboration
• 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

Publications and helpful links

General Publications

• 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. eCollection 2013.

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (ACTUAL): March 1, 2013
• Study Completion (ACTUAL): September 1, 2013

Study Registration Dates

• First Submitted: February 13, 2011
• First Submitted That Met QC Criteria: February 14, 2011
• First Posted (ESTIMATE): February 15, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): December 18, 2013
• Last Update Submitted That Met QC Criteria: December 17, 2013
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Keywords: HIV-1; immune; observational; restoration
• Additional Relevant MeSH Terms: Infections
• Other Study ID Numbers: HIVNAT 136