Ignite Creation Date:
2025-12-25 @ 2:13 AM
Ignite Modification Date:
2026-01-03 @ 11:55 PM
Study NCT ID:
NCT01232660
Status:
UNKNOWN
Last Update Posted:
2014-02-11
First Post:
2010-10-29
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Hydroxychloroquine for Discordant CD4 Responders on Highly Active Antiretroviral Therapy (HAART)
Sponsor:
St Stephens Aids Trust
Organization:
Study Overview
Official Title:
The Immunological Impact of Adding Hydroxychloroquine in Patients With Discordant CD4+ Cell Responses to Suppressive HAART: A Phase I Pilot Study.
Status:
UNKNOWN
Status Verified Date:
2014-02
Last Known Status:
RECRUITING
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:
SSAT039
Brief Summary:
The purpose of the study is to examine the effects of adding a drug called hydroxychloroquine, usually used to treat rheumatoid arthritis, to patients' usual antiretroviral combination. HIV causes activation of some parts of the immune system and this immune activation may persist despite effective antiretroviral therapy. Ongoing activation may be responsible for poor CD4 rise on antiretroviral therapy and for some HIV-related complications. Drugs like hydroxychloroquine work by inhibiting immune activation.
The study will primarily investigate the effect of adding this medication on immunological parameters (particularly CD4 count), on other safety parameters (such as cholesterol), patients' side effects and viral load.
If you decide to take part, the duration of your involvement in the study will be 24 weeks plus two screening visits up to 84 days prior to the start of the study and a follow up visit.
The study will primarily investigate the effect of adding this medication on immunological parameters (particularly CD4 count), on other safety parameters (such as cholesterol), patients' side effects and viral load.
If you decide to take part, the duration of your involvement in the study will be 24 weeks plus two screening visits up to 84 days prior to the start of the study and a follow up visit.
Detailed Description:
Studies exploring changes in antiretrovirals or addition of antiretrovirals from new classes in patients with discordant immune response to suppressive HAART have, in general, yielded disappointing results.
The addition of the antiretroviral maraviroc (a CCR5 antagonist) in patients who had been on suppressive HAART for at least a year but with a CD4 count less than 250 (and not rising) yielded no improvement in CD4 counts in 6 individuals after approximately 5 months.
A small study investigating the benefit of switching to lopinavir/ritonavir (predominantly from NNRTI-based therapy) showed a significant improvement in CD4 cell count with a reduction in cell apoptosis at 6 months.However, data for other switches are lacking and lopinavir/ritonavir may not be a preferred switch option due to gastrointestinal tolerability and an increased risk of myocardial infarction in cohort analyses.
Chronic HIV infection is characterised by gradual loss of CD4 T-cells by direct (virus mediated CD4 death) and indirect mechanisms. Increased immune activation is an indirect mechanism that is central to CD4 T-cell loss. In observational studies, the level of immune activation is associated with the rate of CD4 decline and in patients taking antiretroviral therapy (with or without complete viral suppression) the extent of CD4 recovery is associated with the degree of immune activation.
Immune activation has also been shown to correlate with disease progression and survival. The causes of generalized immune activation in HIV are not fully understood but may be related to nef or gp120.
Hydroxychloroquine \[Plaquanil®\] is licensed to treat rheumatoid arthritis and other inflammatory conditions; it is related to the antimalarial chloroquine.
Hydroxychloroquine and chloroquine have long been used as immunomodulatory therapies for T-cell mediated disorders. The exact mechanisms of hydroxychloroquine are not fully understood, but the agent appears to affect T-cell proliferation and signalling. Hydroxychloroquine also inhibits T-cell proliferative responses and production of pro-inflammatory cytokines IL-1 and IL-6.
Hydroxychloroquine and chloroquine have been shown to inhibit HIV replication, regardless of viral clade or co-receptor tropism, and promote CD4 immune protection.
Three small clinical trials of hydroxychloroquine have been reported in HIV-infected patients. Hydroxychloroquine was associated with small to modest reductions in viral load both as monotherapy and as part of combination therapy. In one of these studies, hydroxychloroquine was compared with zidovudine in HIV-infected patients and patients in both groups had reduced levels of plasma HIV-1 RNA and serum p24 antigen after 16 weeks. Interleukin-6 (an inflammatory cytokine associated with increased risk of mortality in cohort studies of HIV) levels were significantly reduced in the hydroxychloroquine group but not in the zidovudine group.
The usual minimum effective dose of hydroxychloroquine is 400mg once daily (administered as two 200mg film-coated tablets) administered orally. This is also the dose selected for an ongoing Medical Research Council study investigating the immune benefits of hydroxychloroquine in treatment-naive patients not needing to start antiretrovirals. Hydroxychloroquine is cumulative in action and requires several weeks to exert its beneficial effects; for rheumatic disease, treatment should be discontinued if there is no improvement by 6 months. On this basis we feel that 3 months is sufficient time to detect most improvement in immune activation and 6 months sufficient time to observe any benefits if they occur. The maximum recommended dose of hydroxychloroquine is 6.5mg/kg/day.
The addition of the antiretroviral maraviroc (a CCR5 antagonist) in patients who had been on suppressive HAART for at least a year but with a CD4 count less than 250 (and not rising) yielded no improvement in CD4 counts in 6 individuals after approximately 5 months.
A small study investigating the benefit of switching to lopinavir/ritonavir (predominantly from NNRTI-based therapy) showed a significant improvement in CD4 cell count with a reduction in cell apoptosis at 6 months.However, data for other switches are lacking and lopinavir/ritonavir may not be a preferred switch option due to gastrointestinal tolerability and an increased risk of myocardial infarction in cohort analyses.
Chronic HIV infection is characterised by gradual loss of CD4 T-cells by direct (virus mediated CD4 death) and indirect mechanisms. Increased immune activation is an indirect mechanism that is central to CD4 T-cell loss. In observational studies, the level of immune activation is associated with the rate of CD4 decline and in patients taking antiretroviral therapy (with or without complete viral suppression) the extent of CD4 recovery is associated with the degree of immune activation.
Immune activation has also been shown to correlate with disease progression and survival. The causes of generalized immune activation in HIV are not fully understood but may be related to nef or gp120.
Hydroxychloroquine \[Plaquanil®\] is licensed to treat rheumatoid arthritis and other inflammatory conditions; it is related to the antimalarial chloroquine.
Hydroxychloroquine and chloroquine have long been used as immunomodulatory therapies for T-cell mediated disorders. The exact mechanisms of hydroxychloroquine are not fully understood, but the agent appears to affect T-cell proliferation and signalling. Hydroxychloroquine also inhibits T-cell proliferative responses and production of pro-inflammatory cytokines IL-1 and IL-6.
Hydroxychloroquine and chloroquine have been shown to inhibit HIV replication, regardless of viral clade or co-receptor tropism, and promote CD4 immune protection.
Three small clinical trials of hydroxychloroquine have been reported in HIV-infected patients. Hydroxychloroquine was associated with small to modest reductions in viral load both as monotherapy and as part of combination therapy. In one of these studies, hydroxychloroquine was compared with zidovudine in HIV-infected patients and patients in both groups had reduced levels of plasma HIV-1 RNA and serum p24 antigen after 16 weeks. Interleukin-6 (an inflammatory cytokine associated with increased risk of mortality in cohort studies of HIV) levels were significantly reduced in the hydroxychloroquine group but not in the zidovudine group.
The usual minimum effective dose of hydroxychloroquine is 400mg once daily (administered as two 200mg film-coated tablets) administered orally. This is also the dose selected for an ongoing Medical Research Council study investigating the immune benefits of hydroxychloroquine in treatment-naive patients not needing to start antiretrovirals. Hydroxychloroquine is cumulative in action and requires several weeks to exert its beneficial effects; for rheumatic disease, treatment should be discontinued if there is no improvement by 6 months. On this basis we feel that 3 months is sufficient time to detect most improvement in immune activation and 6 months sufficient time to observe any benefits if they occur. The maximum recommended dose of hydroxychloroquine is 6.5mg/kg/day.
Study Oversight
Has Oversight DMC:
False
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?: