Structured Treatment Interruption for HIV Patients With Virologic Failure

Not Applicable

Completed

• Conditions: HIV

• Registration Number: NCT00188851
• Lead Sponsor: University Health Network, Toronto

Brief 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.

Detailed 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.

Study Timeline

• Study Start: 2001-01
• Status Verified: 2005-09
• Study First Submitted: 2005-09-12
• Study First Submitted QC: 2005-09-12
• Last Update Submitted: 2005-09-12
• Study First Posted: 2005-09-16
• Last Update Posted: 2005-09-16
• Study Completion: 2005-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 196

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.

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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)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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.
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
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).
5. To determine the impact of the STI on quality of life measures.
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.