Ignite Creation Date:
2024-05-06 @ 6:37 PM
Last Modification Date:
2024-10-26 @ 2:51 PM
Study NCT ID:
NCT05728996
Status:
RECRUITING
Last Update Posted:
2023-02-15
First Post:
2023-02-06
Brief Title:
Netherlands Cohort Study on Acute HIV Infection
Sponsor:
Prof Jan Prins
Organization:
Academisch Medisch Centrum - Universiteit van Amsterdam AMC-UvA
Study Overview
Official Title:
Netherlands Cohort Study on Acute HIV Infection
Status:
RECRUITING
Status Verified Date:
2023-02
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:
NOVA
Brief Summary:
Investigation of the size variability and localization of the pro viral reservoir and the properties of HIV-specific immune response related to post-treatment viral remission achievement and or duration In addition we will study the factors that determine latency in the different host cells their sensitivity to induction of replication competent virus by various agents and the potential application of these agents in post-treatment viral remission
This all will be studied in patients included during acute phase of the infection who start antiretroviral therapy immediately upon diagnosis
This all will be studied in patients included during acute phase of the infection who start antiretroviral therapy immediately upon diagnosis
Detailed Description:
Rationale There is renewed interest in finding a cure for HIV infection Recent studies show that in a select group of individuals the initiation of combination anti-retroviral therapy cART during the early phase of infection results in long-term absence of viremia following treatment interruption after prolonged treatment These patients are described as having achieved a post-treatment viral remission There are many unsolved issues regarding the question which virological and immunological factors determine which individuals achieve a post-treatment viral remission First studies suggest that the early reduction of viral reservoir size and potential accompanying preservation of immune function may be important factors Furthermore patients that initiate cART during acute infection are potential candidates for additional therapeutic strategies such as latency reversing agents LRAs or therapeutic vaccination
Objectives The primary objective of the NOVA study is the establishment of a prospective cohort study of patients that initiate cART during the acute infection phase aiming at achieving post-treatment viral remission The secondary objective is to characterize the viro-immunological factors that correlate with achievement of post-treatment viral remission for several years in these patients
Study design Prospective cohort study Study population The study population includes patients diagnosed with an AHI Fiebig stage I-V 20 in each stage As a control group only for comparison of the lymph node viral reservoir and immune responses after 3 years of cART 20 age-matched patients will be included who start cART in the chronic phase of infection This control group is recruited to provide PBMCs and a LN sample for comparison purposes Patients will be recruited over a period of 5 consecutive years
Intervention Patients diagnosed with an acute HIV infection AHI are offered immediate standard first-line cART In consenting patients at several time points samples will be obtained to analyze the size and characteristics of the viral reservoir and the accompanying immune function Three groups are assembled based on the preparedness of individual patients to participate in the extensiveness of sampling Patients that accept early treatment and follow-up but decline additional blood and tissue sampling lymph node GALT and cerebral spinal fluid CSF are included in group 1 standard and only routine diagnostic procedures are performed Patients willing to undergo in addition to routine monitoring leukapheresis semen and blood sampling for PBMC and virological analyses are included in group 2 less-invasive In group 3 extended additional tissue and CSF sampling will be performed for the proposed viro-immunological analyses
Main study parameters endpoints We will investigate the size variability and localization of the pro viral reservoir and the properties of HIV-specific immune response and relate these to post-treatment viral remission achievement and or duration In addition we will study the factors that determine latency in the different host cells their sensitivity to induction of replication competent virus by various agents and the potential application of these agents in post-treatment viral remission
This set up allows to guide the duration of cART based on viro-immunological parameters and to adjust cART in case better cART strategies may become available in the future Furthermore based on the available data that show preservation of immunity and reduction in viral reservoir size the AHI patients that start therapy early may have better responses to future cure strategies such as therapeutic vaccination or LRAs
Nature and extent of the burden and risks associated with participation benefit and group relatedness Offering treatment in early HIV infection is currently recommended in clinical guidelines for treatment of HIV infection 1 This recommendation is based on studies showing improvement of markers of disease progression 23 decrease of severity of acute disease lowering of the viral setpoint associated with disease progression 456 and a reduction in size of the viral reservoir 7 The burden and risks associated with study participation are related to tissue sampling lymph node excision biopsies sigmoid biopsies and lumbar puncture at three and leukapheresis at two timepoints during the study week 0 baseline week 24 and 3 years The risks of sampling are considered minimal see also section on sampling Furthermore since potential discontinuation of cART in future can only be guided by size of tissue viral reservoir the sampling is considered to be necessary for treatment guidance In order to minimize burden associated with study visits we aim to combine visits for routine clinical care with routine clinical visits
Objectives The primary objective of the NOVA study is the establishment of a prospective cohort study of patients that initiate cART during the acute infection phase aiming at achieving post-treatment viral remission The secondary objective is to characterize the viro-immunological factors that correlate with achievement of post-treatment viral remission for several years in these patients
Study design Prospective cohort study Study population The study population includes patients diagnosed with an AHI Fiebig stage I-V 20 in each stage As a control group only for comparison of the lymph node viral reservoir and immune responses after 3 years of cART 20 age-matched patients will be included who start cART in the chronic phase of infection This control group is recruited to provide PBMCs and a LN sample for comparison purposes Patients will be recruited over a period of 5 consecutive years
Intervention Patients diagnosed with an acute HIV infection AHI are offered immediate standard first-line cART In consenting patients at several time points samples will be obtained to analyze the size and characteristics of the viral reservoir and the accompanying immune function Three groups are assembled based on the preparedness of individual patients to participate in the extensiveness of sampling Patients that accept early treatment and follow-up but decline additional blood and tissue sampling lymph node GALT and cerebral spinal fluid CSF are included in group 1 standard and only routine diagnostic procedures are performed Patients willing to undergo in addition to routine monitoring leukapheresis semen and blood sampling for PBMC and virological analyses are included in group 2 less-invasive In group 3 extended additional tissue and CSF sampling will be performed for the proposed viro-immunological analyses
Main study parameters endpoints We will investigate the size variability and localization of the pro viral reservoir and the properties of HIV-specific immune response and relate these to post-treatment viral remission achievement and or duration In addition we will study the factors that determine latency in the different host cells their sensitivity to induction of replication competent virus by various agents and the potential application of these agents in post-treatment viral remission
This set up allows to guide the duration of cART based on viro-immunological parameters and to adjust cART in case better cART strategies may become available in the future Furthermore based on the available data that show preservation of immunity and reduction in viral reservoir size the AHI patients that start therapy early may have better responses to future cure strategies such as therapeutic vaccination or LRAs
Nature and extent of the burden and risks associated with participation benefit and group relatedness Offering treatment in early HIV infection is currently recommended in clinical guidelines for treatment of HIV infection 1 This recommendation is based on studies showing improvement of markers of disease progression 23 decrease of severity of acute disease lowering of the viral setpoint associated with disease progression 456 and a reduction in size of the viral reservoir 7 The burden and risks associated with study participation are related to tissue sampling lymph node excision biopsies sigmoid biopsies and lumbar puncture at three and leukapheresis at two timepoints during the study week 0 baseline week 24 and 3 years The risks of sampling are considered minimal see also section on sampling Furthermore since potential discontinuation of cART in future can only be guided by size of tissue viral reservoir the sampling is considered to be necessary for treatment guidance In order to minimize burden associated with study visits we aim to combine visits for routine clinical care with routine clinical visits
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None