HIV Immune Restoration Clinical Trial
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)
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 Model: Cohort, Time Perspective: Prospective