Ignite Creation Date:
2024-05-05 @ 4:59 PM
Last Modification Date:
2024-10-26 @ 9:26 AM
Study NCT ID:
NCT00362687
Status:
COMPLETED
Last Update Posted:
2009-03-31
First Post:
2006-08-09
Brief Title:
GMB Study of Truvada TDFFTC or Emtricitabine FTC Alone Versus HAART Interruption in HIV-Infected Patients With Resistance
Sponsor:
Gilead Sciences
Organization:
Gilead Sciences
Study Overview
Official Title:
GMB Phase IV Multicenter Randomized Open-Label Pilot Study of Truvada TDFFTC or Emtricitabine FTC Alone Versus HAART Interruption in HIV-Infected Patients Who Need to Interrupt HAART and Who Are Infected With HIV Isolates Containing at Least 2 TAMs or K65R and M184V
Status:
COMPLETED
Status Verified Date:
2009-03
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:
Many patients who already harbor drug-resistant HIV require interruption of HAART due to poor compliance poor quality of life toxicity or development of resistance In these patients interruption of HAART has a negative impact on patient immune status due to the reemergence of wild-type virus which is in general more pathogenic than HIV isolates containing resistance mutations There is a need for bridging antiretroviral regimens that might prolong time off conventional HAART whilst waiting for a new regimen that is either fully suppressive or less toxic or less demanding for the patient
Detailed Description:
Virological failure associated with the appearance of resistant mutations is still common in patients receiving HAART When HAART fails patients and clinicians can chose from three different courses of action
1 Switch therapy to a new salvage regimen based on the results of resistance testing
Success of the new salvage regimen is maximized if the new regimen includes antiretroviral drugs without cross-resistance with previous failed drugs or preferablynew classes of drugs In general rescue regimens are more complicated for patients due to its higher pill burden more frequent dosing and sometimes need for parenteral therapy Enfuvirtide
2 Stop therapy This strategy is feasible in patient with relatively preserved immune function Time off antiretroviral therapy would be highly dependent on previous nadir CD4 cell count the lowest the nadir the more rapidly patients loses CD4 cells In patients with multidrug resistant virus this strategy is used with the goal of achieving virus reversion towards wild-type forms Reversion towards wild-type virus would theoretically resensitize HIV to prior failed drugs Unfortunately a number of investigations have suggested that the loss of CD4 cell count occurred during the time off therapy might not be regained after starting rescue therapy In addition reversion towards wild type virus does not appear to be associated with a more favourable outcome of rescue therapy
3 Maintain failing therapy This strategy has the potential advantage of decreasing the rate of CD4 cell loss It is known that certain mutations of HIV decrease viral fitness and produce a less pathogenic virus Consequently compared to wild-type virus CD4 destruction is decreased in the presence of resistance mutations The very important risk inherent to this strategy is the accumulation of new antiretroviral mutations if the regimen is maintained Due to cross-resistance among antiretroviral drugs accumulation of new mutations decreases the chances of success of a new salvage regimen
Choosing among these three different strategies depends on a number of important factors
1 Availability of antiretroviral drugs active against resistant HIV isolates Clinicians would be more prone to switch to a new salvage regimen if the new regimen contains a new class of drugs andor at least three drugs without cross resistance with the antiretroviral included in the failing regimen This scenario is very likely after first or second regimen failure However after third regimen failure the possibilities of including at least three active drugs dramatically decrease For deep salvage the possibilities of constructing a viable rescue regimen often depends on enrolling the patient in a clinical trial of a new antiretroviral for example CCR5 inhibitors Enrolment in the trial very often implies that patients have to wait for an undefined period of time until the trial starts
2 Willingness of patient to switch to a more complicated regimen After second regimen failure rescue therapies involve a higher pill burden more frequent dosing and in a substantial number of cases the need of parenteral therapy with enfuvirtide In this situation it is possible that the patient prefer not to start the new therapy due to the negative impact of the new regimen in his quality of life
3 Immune status of the patient In patients with low CD4 cell count stopping therapy can put the patient at risk of developing an opportunistic disease In general patients and clinicians are reluctant to stop therapy if the current CD4 cell count is below 200-250 cellsmL
Apart from the setting of virological failure HAART interruption might be needed in patients with well controlled viral replication HIV viremia persistently below 50 copies mL Possible reasons for HAART interruption in this scenario are
1 Toxicity of current regimen
2 Patient desire for example travel abroad
3 Poor quality of life related to treatment issues
4 Poor adherence to current HAART regimen and an impending risk of developing resistance mutations When a patient stop HAART due to these reasons wild-type HIV re-emerges with the consequent loss of CD4 cells Depending on the immune status of the patient and prior CD4 cell nadir time off therapy might be quite limited
1 Switch therapy to a new salvage regimen based on the results of resistance testing
Success of the new salvage regimen is maximized if the new regimen includes antiretroviral drugs without cross-resistance with previous failed drugs or preferablynew classes of drugs In general rescue regimens are more complicated for patients due to its higher pill burden more frequent dosing and sometimes need for parenteral therapy Enfuvirtide
2 Stop therapy This strategy is feasible in patient with relatively preserved immune function Time off antiretroviral therapy would be highly dependent on previous nadir CD4 cell count the lowest the nadir the more rapidly patients loses CD4 cells In patients with multidrug resistant virus this strategy is used with the goal of achieving virus reversion towards wild-type forms Reversion towards wild-type virus would theoretically resensitize HIV to prior failed drugs Unfortunately a number of investigations have suggested that the loss of CD4 cell count occurred during the time off therapy might not be regained after starting rescue therapy In addition reversion towards wild type virus does not appear to be associated with a more favourable outcome of rescue therapy
3 Maintain failing therapy This strategy has the potential advantage of decreasing the rate of CD4 cell loss It is known that certain mutations of HIV decrease viral fitness and produce a less pathogenic virus Consequently compared to wild-type virus CD4 destruction is decreased in the presence of resistance mutations The very important risk inherent to this strategy is the accumulation of new antiretroviral mutations if the regimen is maintained Due to cross-resistance among antiretroviral drugs accumulation of new mutations decreases the chances of success of a new salvage regimen
Choosing among these three different strategies depends on a number of important factors
1 Availability of antiretroviral drugs active against resistant HIV isolates Clinicians would be more prone to switch to a new salvage regimen if the new regimen contains a new class of drugs andor at least three drugs without cross resistance with the antiretroviral included in the failing regimen This scenario is very likely after first or second regimen failure However after third regimen failure the possibilities of including at least three active drugs dramatically decrease For deep salvage the possibilities of constructing a viable rescue regimen often depends on enrolling the patient in a clinical trial of a new antiretroviral for example CCR5 inhibitors Enrolment in the trial very often implies that patients have to wait for an undefined period of time until the trial starts
2 Willingness of patient to switch to a more complicated regimen After second regimen failure rescue therapies involve a higher pill burden more frequent dosing and in a substantial number of cases the need of parenteral therapy with enfuvirtide In this situation it is possible that the patient prefer not to start the new therapy due to the negative impact of the new regimen in his quality of life
3 Immune status of the patient In patients with low CD4 cell count stopping therapy can put the patient at risk of developing an opportunistic disease In general patients and clinicians are reluctant to stop therapy if the current CD4 cell count is below 200-250 cellsmL
Apart from the setting of virological failure HAART interruption might be needed in patients with well controlled viral replication HIV viremia persistently below 50 copies mL Possible reasons for HAART interruption in this scenario are
1 Toxicity of current regimen
2 Patient desire for example travel abroad
3 Poor quality of life related to treatment issues
4 Poor adherence to current HAART regimen and an impending risk of developing resistance mutations When a patient stop HAART due to these reasons wild-type HIV re-emerges with the consequent loss of CD4 cells Depending on the immune status of the patient and prior CD4 cell nadir time off therapy might be quite limited
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