Ignite Creation Date:
2024-05-06 @ 7:54 AM
Last Modification Date:
2024-10-26 @ 11:54 AM
Study NCT ID:
NCT02628340
Status:
COMPLETED
Last Update Posted:
2016-08-02
First Post:
2015-02-04
Brief Title:
Comprehensive Analysis of HIV Reservoirs in Chronically Infected HIV-1 Treated Patients
Sponsor:
Centre de Recherches et dEtude sur la Pathologie Tropicale et le Sida
Organization:
Centre de Recherches et dEtude sur la Pathologie Tropicale et le Sida
Study Overview
Official Title:
Comprehensive Analysis of HIV Reservoirs in Chronically Infected HIV-1 Treated Patients With a Low Total Cell-associated Blood HIV-DNA
Status:
COMPLETED
Status Verified Date:
2016-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
RESACHRON
Brief Summary:
HIV infection can be efficiently controlled by antiretroviral therapy ART with in 2013 nearly 85 of patients having a suppressed viremia but HIV cannot however be eradicated with ART alone 1 Overall HIV has moved from a fatal to a chronic disease provided treatment is maintained life-long Despite major improvement in antiretroviral drugs in terms of efficacy tolerability and simplicity life-long therapy is still associated with drug toxicity Several drugs or drug classes which have historically saved lives since 1996 and are currently widely used such as protease inhibitors and nucleosides analogues are associated with long-term toxicities and increased incidence of comorbidities
Currently worldwide there is an approximated 10 millions of HIV infected patients under cART This number should increase in the next years as most recent guidelines recommend earlier therapy given the benefits in terms of disease progression and prevention of transmission Because of the increasing number of patients who will be under cART in the future the cumulative ART toxicity the difficulties to access ART in some areas of the world the fatigue expressed by patients about ART and the cost issues there is an urgent need to search for HIV CURE To date only two cases of sterilizing HIV cure were reported so far the famous Berlin Patient after two homozygous Delta32-CCR5 bone-marrow grafts for an acute leukemia 2 and the Mississipi baby after very early initiation of cART 31 hours after delivery 3 However those cases of sterilizing HIV cure remain exceptional and the alternative objective of a functional HIV cure appears to be more realistic though still described in rare groups of patients like Elite controllers EC and post treatment controllers PTC patients In addition new and complex therapeutic strategies are currently proposed to try purging the HIV reservoirs but none of them proved so far able to reach this goal
Therefore the objective of finding a Cure to HIV 4 requires first to better understand the basic mechanisms of the persistence of HIV reservoirs in the population of chronically-infected fully-suppressed HIV patients in order to define future therapeutic strategies
Currently worldwide there is an approximated 10 millions of HIV infected patients under cART This number should increase in the next years as most recent guidelines recommend earlier therapy given the benefits in terms of disease progression and prevention of transmission Because of the increasing number of patients who will be under cART in the future the cumulative ART toxicity the difficulties to access ART in some areas of the world the fatigue expressed by patients about ART and the cost issues there is an urgent need to search for HIV CURE To date only two cases of sterilizing HIV cure were reported so far the famous Berlin Patient after two homozygous Delta32-CCR5 bone-marrow grafts for an acute leukemia 2 and the Mississipi baby after very early initiation of cART 31 hours after delivery 3 However those cases of sterilizing HIV cure remain exceptional and the alternative objective of a functional HIV cure appears to be more realistic though still described in rare groups of patients like Elite controllers EC and post treatment controllers PTC patients In addition new and complex therapeutic strategies are currently proposed to try purging the HIV reservoirs but none of them proved so far able to reach this goal
Therefore the objective of finding a Cure to HIV 4 requires first to better understand the basic mechanisms of the persistence of HIV reservoirs in the population of chronically-infected fully-suppressed HIV patients in order to define future therapeutic strategies
Detailed Description:
Extremely low levels of HIV reservoirs are achievable in some chronically-infected patients durably controlled with cART Despite the multiplicity and heterogeneity of factors governing the persistence of HIV reservoirs such low levels of HIV reservoirs seem necessary though probably not sufficient to reach the status of functional cure defined by virus control in the absence of treatment The mechanisms associated with these low HIV reservoirs in chronic treated infection are unknown but might involve a low immune activation and inflammatory environment and deleterious HIV mutations Understanding those mechanisms will provide novel clues for future strategies aiming at obtaining an HIV Cure
The main objective of RESACHRON Study is to define in chronically infected patients with suppressed viremia cART and extremely low levels of HIV reservoirs the viral and cellular mechanisms underlying the persistence the size and the distribution of these HIV reservoirs among the various CD4 T cell-subpopulations via a comprehensive analysis using innovative highly miniaturized and complementary immunological and virological assays
Our first hypothesis is that HIV reservoirs persist even in patients with low to undetectable HIV-DNA in the total PBMCs and can be detected ex vivo or give rise to HIV production in some CD4 T cells subsets due to the mean 10-fold enrichment in peripheral blood TCM and TTM cells The sorting of the various sorted CD4 TN TCM TTM TEM and other key subsets will thus allow to test whether and in which subset
1 the virus genome is intact or contains deletions interfering with its replicative capacity
2 HIV production can be induced in vitro after distinct activation signals
3 HIV transcripts are detectable ex-vivo
4 Low immune activation and inflammatory environment is associated with these extremely low HIV reservoirs levels by testing a series of plasma pro-inflammatory molecules together with cell surface activation markers and intra-cellular transcriptional signatures
The main objective of RESACHRON Study is to define in chronically infected patients with suppressed viremia cART and extremely low levels of HIV reservoirs the viral and cellular mechanisms underlying the persistence the size and the distribution of these HIV reservoirs among the various CD4 T cell-subpopulations via a comprehensive analysis using innovative highly miniaturized and complementary immunological and virological assays
Our first hypothesis is that HIV reservoirs persist even in patients with low to undetectable HIV-DNA in the total PBMCs and can be detected ex vivo or give rise to HIV production in some CD4 T cells subsets due to the mean 10-fold enrichment in peripheral blood TCM and TTM cells The sorting of the various sorted CD4 TN TCM TTM TEM and other key subsets will thus allow to test whether and in which subset
1 the virus genome is intact or contains deletions interfering with its replicative capacity
2 HIV production can be induced in vitro after distinct activation signals
3 HIV transcripts are detectable ex-vivo
4 Low immune activation and inflammatory environment is associated with these extremely low HIV reservoirs levels by testing a series of plasma pro-inflammatory molecules together with cell surface activation markers and intra-cellular transcriptional signatures
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None