Ignite Creation Date:
2024-05-05 @ 11:53 AM
Last Modification Date:
2024-10-26 @ 9:15 AM
Study NCT ID:
NCT00160329
Status:
COMPLETED
Last Update Posted:
2011-07-21
First Post:
2005-09-08
Brief Title:
Atazanavir or Boosted Atazanavir Substitution for Ritonavir Boosted PI in Patients With Hyperlipidemia
Sponsor:
Stanford University
Organization:
Stanford University
Study Overview
Official Title:
The De-Escalate Trial Atazanavir or AtazanavirRitonavir Substitution for Ritonavir Boosted PI Therapy in HIV-Infected Individuals Experiencing Ongoing HIV Viremia and Hyperlipidemia A Randomized Controlled Pilot Study
Status:
COMPLETED
Status Verified Date:
2011-07
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:
None
Brief Summary:
The study is looking to compare the impact of lipid levels and HIV viral loads between three different drug regimens Continuing current regimen ritonavir boosted regimen Switching to Atazanavir or Switching to Atazanavir in combination to Ritonavir
Detailed Description:
Study Overview
This is a randomized controlled pilot study to compare the safety and efficacy of substitution of atazanavir ATV or ATVRTV for ritonavir boosted PI in patients with ongoing viremia who are experiencing hyperlipidemia andor requiring treatment with lipid lowering agents In this study 60 subjects on a ritonavir boosted PI-containing antiretroviral regimen who are experiencing hyperlipidemia and ongoing HIV viremia will be randomized in a 111 ratio to either switch the ritonavir boosted PI component of the antiretroviral regimen to ATV or ATVRTV or continue the ritonavir boosted PI-based regimen
No other changes in the antiretroviral regimen will be allowed for the first 12 weeks Thereafter the investigator may change background ARVs based on the results of the screening resistance test No new class of antiretrovirals will be allowed to be added through 48 weeks Subjects will be monitored closely over 48 weeks with careful assessment of CD4 profile viral loads and lipid profiles as well as drug resistance and replication capacity Stopping rules will be implemented based on CD4 and viral load profile to ensure subject safety The objective of this study is to determine whether protease inhibitor regimens that have less of an adverse impact on lipid profiles can maintain a stable CD4 profile compared to standard ritonavir boosted PI regimens
Background
Antiretroviral regimens that include ritonavir-boosted protease inhibitors are commonly recommended and prescribed particularly in patients with some degree of drug resistance Despite the potency of boosted regimens many HIV-infected patients receiving these regimens have incomplete viral suppression and yet maintain clinical stability and CD4 counts above nadir levels the so called CD4HIV disconnect state It is likely that this state of CD4HIV discordance is due in part to the maintenance of drug resistant HIV virus that is relatively unfit that is its replication capacity and ability to infect and destroy CD4 cells is compromised The selective pressure exerted by antiretroviral therapy appears to be important in maintaining these drug resistant but relatively unfit quasispecies It has been shown that even patients with CD4 counts below 50 cellscc and ongoing viremia maintain a clinical benefit from continued therapy
Unfortunately lipid abnormalities are commonly seen in patients receiving boosted PI regimens For example in a clinical trial in which lopinavirritonavir LPVr was given to treatment naïve subjects approximately 13 developed grade 2 or higher lipid abnormalities over 48 weeks There is a growing concern that these lipid abnormalities will increase the risk of cardiovascular morbidity and mortality In fact recent data suggest an increased risk of cardiovascular morbidity and mortality related to HIV infection andor antiretroviral therapy There are increasing efforts directed at minimizing long-term toxicities of antiretroviral therapy while maintaining its clinical benefit Witness the high degree of interest in treatment interruptions as a strategy to limit toxicities associated with long-term antiretroviral therapy
Atazanavir ATV a recently approved PI appears to have little to no impact on the lipid profile in subjects enrolled in clinical trials Other advantages with atazanavir are its dosing schedule and overall tolerability Furthermore recent studies using ritonavir-boosted ATV also show favorable lipid effects compared to LPVr Ritonavir boosting provides higher drug levels and therefore may improve the potency of ATV especially against PI-resistant virus
This is a randomized controlled pilot study to compare the safety and efficacy of substitution of atazanavir ATV or ATVRTV for ritonavir boosted PI in patients with ongoing viremia who are experiencing hyperlipidemia andor requiring treatment with lipid lowering agents In this study 60 subjects on a ritonavir boosted PI-containing antiretroviral regimen who are experiencing hyperlipidemia and ongoing HIV viremia will be randomized in a 111 ratio to either switch the ritonavir boosted PI component of the antiretroviral regimen to ATV or ATVRTV or continue the ritonavir boosted PI-based regimen
No other changes in the antiretroviral regimen will be allowed for the first 12 weeks Thereafter the investigator may change background ARVs based on the results of the screening resistance test No new class of antiretrovirals will be allowed to be added through 48 weeks Subjects will be monitored closely over 48 weeks with careful assessment of CD4 profile viral loads and lipid profiles as well as drug resistance and replication capacity Stopping rules will be implemented based on CD4 and viral load profile to ensure subject safety The objective of this study is to determine whether protease inhibitor regimens that have less of an adverse impact on lipid profiles can maintain a stable CD4 profile compared to standard ritonavir boosted PI regimens
Background
Antiretroviral regimens that include ritonavir-boosted protease inhibitors are commonly recommended and prescribed particularly in patients with some degree of drug resistance Despite the potency of boosted regimens many HIV-infected patients receiving these regimens have incomplete viral suppression and yet maintain clinical stability and CD4 counts above nadir levels the so called CD4HIV disconnect state It is likely that this state of CD4HIV discordance is due in part to the maintenance of drug resistant HIV virus that is relatively unfit that is its replication capacity and ability to infect and destroy CD4 cells is compromised The selective pressure exerted by antiretroviral therapy appears to be important in maintaining these drug resistant but relatively unfit quasispecies It has been shown that even patients with CD4 counts below 50 cellscc and ongoing viremia maintain a clinical benefit from continued therapy
Unfortunately lipid abnormalities are commonly seen in patients receiving boosted PI regimens For example in a clinical trial in which lopinavirritonavir LPVr was given to treatment naïve subjects approximately 13 developed grade 2 or higher lipid abnormalities over 48 weeks There is a growing concern that these lipid abnormalities will increase the risk of cardiovascular morbidity and mortality In fact recent data suggest an increased risk of cardiovascular morbidity and mortality related to HIV infection andor antiretroviral therapy There are increasing efforts directed at minimizing long-term toxicities of antiretroviral therapy while maintaining its clinical benefit Witness the high degree of interest in treatment interruptions as a strategy to limit toxicities associated with long-term antiretroviral therapy
Atazanavir ATV a recently approved PI appears to have little to no impact on the lipid profile in subjects enrolled in clinical trials Other advantages with atazanavir are its dosing schedule and overall tolerability Furthermore recent studies using ritonavir-boosted ATV also show favorable lipid effects compared to LPVr Ritonavir boosting provides higher drug levels and therefore may improve the potency of ATV especially against PI-resistant virus
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
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| IRB 79603 | OTHER | None | None |
| Spo 29750 | OTHER | Stanford University | None |