Structured Treatment Interruption for HIV Patients With Virologic Failure

HIV Clinical Trial

Official title:

A Prospective Randomized Trial of Structured Treatment Interruption(STI) Followed by Initiation of a New Antiretroviral Regimen(ARV) Versus Immediate Switching to a New ARV in HIV-Infected Patients Experiencing Virologic Failure on HAART

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00188851
• Other study ID #: CIHR82716
• Status: Completed
• Phase: N/A
• First received: September 12, 2005
• Last updated: September 12, 2005
• Start date: January 2001
• Est. completion date: November 2005

Study information

• Verified date: September 2005
• Source: University Health Network, Toronto
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the virologic impact of switching treatment-experienced HIV-infected patients with virologic failure to a salvage regimen with or without a 12 week STI prior to the switch.

Hypothesis: A STI prior to starting a salvage regimen will result in an improved virologic response.

Description:

To prospectively determine the virologic impact of switching treatment-experienced HIV-infected patients with virologic failure to a salvage regimen with or without a 12 week STI prior to the switch.

Hypothesis: By withdrawing ARV drug pressure, resistant HIV virus will revert to wild-type. In treatment-experienced HIV patients who experience virologic failure, a STI prior to starting a salvage regimen will result in an improved virologic response and more prolonged vral suppression compared to immediate switching to a new regime.

Interventions:

Immediate Switch to Salvage Therapy: Patients randomized to the control arm will be switched immediately to a salvage regimen using the information from the treatment history and genotype results.

Structured Treatment Interruption: Patients randomized to the STI arm will have their present regimen stopped for 12 weeks and will have a genotype repeated in the 12th week. A salvage regimen will be started at week 12 using the information from the treatment history and baseline genotype results.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 196
• Est. completion date: November 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age > 18 years.

• On therapy with a triple ARV that includes a protease inhibitor and/or non-nucleoside reverse transcriptase inhibitor for the past 3 months with no changes in any agent of the combination in the past 14 days.

• Virologic failure while on the combination as defined by a plasma HIV RNA > 1000 copies/mL measured on 2 occasions at least 4 weeks apart.

• HIV RNA <500,000 copies/mL.

• CD4 cell count must be > 50/mm3

• Patients must not have a present history of opportunistic infections or acute illness requiring treatment within the preceding 30 days.

• The patient has at least two new ARV available based on history, and at least two of these new agents will be included in the new salvage regimen.

Exclusion Criteria:

• Active substance abuse which would interfere with the patient's ability to participate in this trial, or declared non-compliance.

• Pregnancy or breast feeding.

• Patients with any of the following abnormal laboratory test results at screening:· Hemoglobin<80 g/L, neutrophil count<750 cells/mL, Platelet<20,000 /mL· AST or ALT > 5X Upper Limit of Normal (ULN)· Creatinine > 250 umol/L

• End stage organ disease

• Patient with malignancy receiving systemic chemotherapy

• Patient has need for immune modulators (interleukin, interferon, GMCSF etc) or prednisone. This excludes a short course of inhaled or oral steroids for asthma exacerbation)

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV

Intervention

Drug:
• therapeutic management strategy

Locations

Country	Name	City	State
n/a

Sponsors (3)

Lead Sponsor	Collaborator
University Health Network, Toronto	Canadian Institutes of Health Research (CIHR), CIHR Canadian HIV Trials Network

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To prospectively determine the virologic impact of switching treatment-experienced HIV-infected patients with virologic failure to a salvage regimen with or without a 12 week STI prior to the switch.
Secondary	1. To prospectively determine differences in other virologic parameters through follow up between patients being switched to a salvage regimen with or without a STI.
Secondary	2. To prospectively determine differences in change in CD4 count through follow up and at 24, 48 and 60 weeks following randomization between patients being switched to a salvage regimen with or without a STI.
Secondary	3. To prospectively determine differences in the development or reactivation of opportunistic infections and survival between patients being switched to a salvage regimen with or without a STI at 60 weeks following randomization
Secondary	4. To determine the proportion of virus of patients being treated with a STI that converts to wild-type and how that relates to the virologic response (% of patients with undetectable viral load sustained for 3 months).
Secondary	5. To determine the impact of the STI on quality of life measures.
Secondary	6. To determine the genotypic resistance pattern of virus from patients who fail treatment after suppression to <50 copies/mL on the salvage regimen and to compare results in those who do and do not receive an STI.