Clinical trial NCT00188851: Structured Treatment Interruption for HIV Patients With Virologic Failure
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV
Keywords: HIV
salvage regimen
virologic failure
treatment interruption
ARV experienced
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
name: CIHR Canadian HIV Trials Network
First posted: 2005-09-16
Enrollment: 196
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: 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 outcomes:
measure: 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.
measure: 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.
measure: 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
measure: 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).
measure: 5. To determine the impact of the STI on quality of life measures.
measure: 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.
Other outcomes:
Locations:
Study officials:
affiliation: University Health Network, Toronto, On
name: Mona Loutfy, MD
role: STUDY_CHAIR
affiliation: Canadian Trials Network, Vancouver, B.C.
name: Joel Singer, MD
role: STUDY_DIRECTOR
affiliation: Univeristy Health Network, Toronto, On
name: Janet Raboud, Dr.
role: STUDY_DIRECTOR
affiliation: University of Alberta, Edmonton, Alberta
name: Stephen Shafran, MD
role: STUDY_DIRECTOR
affiliation: Ottawa Hospital, Ottawa, On
name: Bill Cameron, MD
role: STUDY_DIRECTOR
affiliation: Clinique Medicale L'Actuel, Montreal, Quebec
name: Sylvie Trottier, MD
role: STUDY_DIRECTOR
affiliation: B.C. Centre of Excellence, Vancouver, B.C.
name: Richard Harrigan, MD
role: STUDY_DIRECTOR
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