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

NCT ID: NCT01296373

Last Updated: 2013-12-18

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 53 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2010-09-30
• Study Completion Date: 2013-09-30

Brief Summary

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.

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.

Conditions

HIV Immune Restoration

Keywords

HIV-1; immune; restoration; observational

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

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

No interventions assigned to this group

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chulalongkorn University

OTHER

Sponsor Role: collaborator

HIV Netherlands Australia Thailand Research Collaboration

NETWORK

Sponsor Role: collaborator

St Vincent's Hospital, Sydney

OTHER

Sponsor Role: collaborator

Kirby Institute

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sarah L Pett, MD

Role: STUDY_DIRECTOR

National Centre in HIV Epidemiology and Clinical Research.

David A Cooper, MD

Role: STUDY_CHAIR

National Centre in HIV Epidemiology and Clinical Research.

Anthony D Kelleher, MD

Role: STUDY_CHAIR

St Vincent's Hospital, Sydney

Denise Hsu, MD

Role: PRINCIPAL_INVESTIGATOR

The HIV Netherlands Australia Thailand Research Collaboration

Jintanat Ananworanich, MD

Role: PRINCIPAL_INVESTIGATOR

The HIV Netherlands Australia Thailand Research Collaboration

Locations

HIV-NAT

Bangkok, , Thailand

Countries

Thailand

References

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.

Reference Type: DERIVED

PMID: 24130889 (View on PubMed)

Other Identifiers

HIVNAT 136

Identifier Type: -

Identifier Source: org_study_id