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

HIV Immune Restoration Clinical Trial

— RESTORE  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01296373
• Other study ID #: HIVNAT 136
• Status: Completed
• Phase: N/A
• First received: February 13, 2011
• Last updated: December 17, 2013
• Start date: September 2010
• Est. completion date: September 2013

Study information

• Verified date: December 2013
• Source: Kirby Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: Thailand: Ministry of Public Health
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 53
• Est. completion date: September 2013
• Est. primary completion date: March 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• HIV Immune Restoration

Locations

Country	Name	City	State
Thailand	HIV-NAT	Bangkok

Sponsors (4)

Lead Sponsor	Collaborator
Kirby Institute	Chulalongkorn University, HIV Netherlands Australia Thailand Research Collaboration, St Vincent's Hospital, Sydney

Country where clinical trial is conducted

Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Longitudnal Changes in CD4+ T-cell with combination antiretoviral therapy		2-3 years	No
Secondary	Longitudinal changes in T-cell subsets with combination antiretroviral therapy		2-3 years	No
Secondary	Longitudinal changes in CD4+ T-cell immune responses to common pathogens during combination antiretroviral therapy		2-3 years	No