HIV InfectionPhase 4SUATNCT01351740
Switch to Unboosted Atazanavir With Tenofovir Study
A Phase 4 study testing atazanavir and atazanavir/ritonavir in people with HIV Infection, run by University of British Columbia at 1 site in Canada.
Trial summary
A drug-drug interaction between the anti-HIV drugs tenofovir DF (TDF) and atazanavir (ATZ) results in lower ATZ plasma levels when the drugs are given together, particularly in patients not taking ritonavir to boost ATZ levels. Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- HIV Infection
- What is being tested?
- atazanavir and atazanavir/ritonavir
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteCanada
- Study dates
- Jul 2011to Dec 2015
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- HIV infected adults at least 19 years of age
- Willing and able to provide informed consent to study participation
- Currently receiving a regimen including atazanavir 300mg/ritonavir 100mg daily with either tenofovir/emtricitabine (FTC) or tenofovir/lamivudine (3TC), for at least 3 months
- Plasma viral load (VL) <40 copies/mL for at least 2 consecutive measurements including the screening value, and < 150 copies/mL continuously for at least 3 months prior to screening
- Current regimen is first antiretroviral regimen, or if not first regimen, no evidence of resistance to any nucleosides (NRTIs) or protease inhibitors (PIs) on previous resistance tests
- Any CD4
Who cannot join
- Clinically significant intolerance or toxicity with current regimen precluding regimen continuation (e.g. intolerance/toxicity to ritonavir necessitating ritonavir discontinuation)
- pregnancy or breast-feeding
- antiretroviral regimen including any nonnucleoside reverse transcriptase inhibitor (nevirapine, efavirenz, or etravirine)
- antiretroviral regimen including any protease inhibitor other than atazanavir and ritonavir
- concomitant treatment with proton pump inhibitors, rifampin, St. John's wort, or garlic supplements. (Antacids and H2 receptor antagonists will be allowed provided their dosing is separated from atazanavir administration by at least 2 and 10 hours, respectively).
Trial locations and contacts
1 site in 1 country.
Canada1 site
Immunodeficiency Clinic, St. Paul's Hospital
Vancouver, British Columbia, V6Z1Y6
About this study
Official title: Switch to Unboosted Atazanavir With Tenofovir (SUAT) Study
A drug-drug interaction between the anti-HIV drugs tenofovir DF (TDF) and atazanavir (ATZ) results in lower ATZ plasma levels when the drugs are given together, particularly in patients not taking ritonavir to boost ATZ levels. Lower plasma drug levels may make the anti-HIV regimen less effective in controlling the HIV virus levels in the blood. For this reason, current treatment guidelines recommend that ATZ always be boosted with ritonavir in regimens also containing TDF. However, withdrawal of ritonavir is often desirable given the tolerability and toxicity issues with this agent, even at the low dose (100 mg daily) used to boost ATZ. For example, ritonavir can cause stomach upset, nausea, diarrhea, high cholesterol levels, and liver enzyme abnormalities.
However, there is evidence that plasma ATZ levels may not predict treatment success on unboosted ATZ regimens, particularly among people whose plasma HIV virus is already under control and unboosted ATZ is being used as a maintenance strategy. In the BC Centre for Excellence in HIV/AIDS Drug Treatment Program (DTP), nearly 100 patients originally treated with ritonavir-boosted ATZ + TDF (+ FTC or 3TC) are receiving successful maintenance therapy with unboosted ATZ and the same TDF-based backbone.
The study will examine the hypothesis that switching to maintenance therapy with unboosted ATZ 400mg daily will have similar 48-week virologic efficacy to continuing ATZ/ritonavir 300/100mg daily among HIV-infected adults with stable viral load suppression on regimens comprising ATZ/ritonavir 300/100mg daily with TDF plus either FTC or 3TC, despite potentially lower ATZ trough levels with the unboosted regimen. In other words, patients whose HIV viral load is undetectable while receiving TDF (+FTC or 3TC) and ATZ/ritonavir will continue to maintain an undetectable viral load after switching to unboosted ATZ without ritonavir, in the same proportions as those continuing on their boosted ATZ/ritonavir regimen.
Read the detailed description
Following a screening visit to establish study eligibility, eligible consenting subjects will be randomized 1:1 to one of the two treatment arms (switch to unboosted ATZ or continue ritonavir-boosted ATZ). Randomized open-label treatment will commence following study procedures at baseline. Participants will be assessed at baseline and at weeks 4, 8, 12, 24, 36, and 48. On-study evaluations will include assessment of adverse clinical events and medication changes; blood tests for HIV viral load, CD4 cell count, standard safety parameters, fasting lipids and glucose, and pregnancy testing (if applicable); and urine tests for urinalysis and albumin to creatinine ratio. In addition, a serum sample will be stored at each visit for possible future testing. A timed plasma sample for measurement of pre-dose trough ATZ levels will be obtained once per subject at 4-8 weeks. Quality of life will be assessed by completion of the MOS-HIV questionnaire at baseline and every 12 weeks. Adherence will be assessed based on prescription refill data.
In case of protocol-defined virologic failure, a plasma sample for ATZ trough level will be collected, and genotypic resistance testing will be performed on plasma samples with viral load >250 copies/mL. Subjects with confirmed virologic failure will be asked to come to the clinic and will have their HIV treatment changed to a more effective regimen, selected based on the results of genotypic testing, as soon as possible.
The anticipated rate of confirmed virologic failure in the control arm is no more than 15% over the 48 weeks of the study. Once at least 20 subjects have been assigned to the experimental (switch) treatment arm, if the observed confirmed virologic failure rate in the experimental arm is greater than twice this rate, i.e. >30%, at any time during the study, the study will be stopped. At this time, subjects in the experimental arm will be reassessed as soon as possible and will resume ritonavir-boosted atazanavir or other effective HIV therapy as appropriate. The failure rate will be reassessed at a minimum after each 20 subjects are enrolled into the experimental (switch) arm.
- Conditions
- HIV Infection
- Being tested
- atazanavir, atazanavir/ritonavir
- Keywords
- HIV, Anti-HIV Agents, HIV Protease Inhibitors
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
atazanavirDrug
switch to unboosted atazanavir 400 mg daily
atazanavir/ritonavirDrug
Continue current regimen of atazanavir 300 mg/ ritonavir 100 mg daily
| Study group | Role | What they receive |
|---|---|---|
| Switch | Experimental | switch to unboosted atazanavir 400mg daily with the same nucleoside (NRTI) backbone Receives: Drug: atazanavir |
| Continuation | Active comparator | continue on current regimen of atazanavir/ritonavir 300mg/100mg with the same nucleoside (NRTI) backbone Receives: Drug: atazanavir/ritonavir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportions of Subjects Experiencing Virologic Failure by Randomized Treatment Arm
For the purposes of the study, virologic failure is defined as either regimen change for any reason, or plasma viral load >400 copies/mL on 2 consecutive measurements >2 weeks apart.
Measured: at or before 48 weeks.
Secondary outcomes (9)
Proportions of Subjects in Each Randomized Treatment Arm With Atazanavir Trough Levels Below 150ng/mL
Therapeutic drug monitoring (TDM) to determine atazanavir trough plasma level will be performed once on all subjects at 4-8 weeks
Measured: 1 month (4-8 weeks)
Proportion of Subjects Experiencing Virologic Failure by Results of 1-month TDM
For the purposes of the study, virologic failure is defined as either regimen change for any reason, or plasma viral load >400 copies/mL on 2 consecutive measurements >2 weeks apart. Comparison will be made between subjects with 1-month (4-8 week) on-study atazanavir trough levels <150ng/mL and those with 1-month (4-8 week) on-study atazanavir trough levels >150ng/mL.
Measured: at or before 48 weeks
Proportions of Subjects Experiencing Virologic Failure by Randomized Treatment Arm
For the purposes of the study, virologic failure is defined as either regimen change for any reason, or plasma viral load >400 copies/mL on 2 consecutive measurements >2 weeks apart.
Measured: at or before 24 weeks.
Proportion of Subjects Experiencing Virologic Failure by Results of 1-month TDM
For the purposes of the study, virologic failure is defined as either regimen change for any reason, or plasma viral load >400 copies/mL on 2 consecutive measurements >2 weeks apart. Comparison will be made between subjects with 1-month (4-8 week) on-study atazanavir trough levels <150ng/mL and those with 1-month (4-8 week) on-study atazanavir trough levels >150ng/mL.
Measured: at or before 24 weeks
CD4 Cell Count Changes (Absolute and Fraction)
Comparison will be made between randomized treatment arms.
Measured: 24 and 48 weeks
Safety (Clinical and Laboratory Adverse Events)
Serious adverse events and discontinuations will be compared between randomized treatment arms
Measured: 24 and 48 weeks
Total Serum Bilirubin Levels
Comparison will be made between randomized treatment arms.
Measured: 24 and 48 weeks
Metabolic Parameters
Comparison will be made between randomized treatment arms with respect to changes in fasting lipids and glucose, highly sensitive C-reactive protein [hsCRP], and apolipoprotein [apo]B, and proportions of subjects developing abnormalities or crossing predefined limits (e.g. NCEP thresholds for lipids)
Measured: 24 and 48 weeks
Quality of Life as Assessed by MOS-HIV
Changes in MOS-HIV scores from baseline will be compared between randomized treatment arms.
Measured: 24 and 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2011 (estimated)
- Study startJul 2011
- Primary completionJan 2015
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionStudies of the same condition, open and under way.
- More trials run by University of British ColumbiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of British Columbia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Marianne Harris, MD, University of British Columbia
- Investigators
- Marianne Harris, MD, Principal investigator, Providence Health Care/ University of British Columbia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01351740
- Sponsor's protocol ID
- H10-03255
- Other IDs
- H10-03255
- Acronym
- SUAT
- Status last verified
- Oct 2017
- First submitted
- 9 May 2011
- Last updated
- 30 Jul 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Harris M, Ganase B, Watson B, Hull MW, Guillemi SA, Zhang W, Saeedi R, Harrigan PR. Efficacy and safety of "unboosting" atazanavir in a randomized controlled trial among HIV-infected patients receiving tenofovir DF. HIV Clin Trials. 2017 Jan;18(1):39-47. doi: 10.1080/15284336.2016.1271503. Epub 2017 Jan 9.
PubMed 28067119
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Switch to Unboosted Atazanavir With Tenofovir (SUAT) Study
- ClinicalTrials.gov ID
- NCT01351740
- Acronym / sponsor ID
- SUAT / H10-03255
- Conditions
- HIV Infection
- Keywords
- HIV, Anti-HIV Agents, HIV Protease Inhibitors
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- University of British ColumbiaUniversity, hospital or other
- Study start
- Jul 2011
- Primary completion
- Jan 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 11 May 2011 (estimated)
- Results
- Posted 30 Jul 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A drug-drug interaction between the anti-HIV drugs tenofovir DF (TDF) and atazanavir (ATZ) results in lower ATZ plasma levels when the drugs are given together, particularly in patients not taking ritonavir to boost ATZ levels. Lower plasma drug levels may make the anti-HIV regimen less effective in controlling the HIV virus levels in the blood. For this reason, current treatment guidelines recommend that ATZ always be boosted with ritonavir in regimens also containing TDF. However, withdrawal of ritonavir is often desirable given the tolerability and toxicity issues with this agent, even at the low dose (100 mg daily) used to boost ATZ. For example, ritonavir can cause stomach upset, nausea, diarrhea, high cholesterol levels, and liver enzyme abnormalities.
However, there is evidence that plasma ATZ levels may not predict treatment success on unboosted ATZ regimens, particularly among people whose plasma HIV virus is already under control and unboosted ATZ is being used as a maintenance strategy. In the BC Centre for Excellence in HIV/AIDS Drug Treatment Program (DTP), nearly 100 patients originally treated with ritonavir-boosted ATZ + TDF (+ FTC or 3TC) are receiving successful maintenance therapy with unboosted ATZ and the same TDF-based backbone.
The study will examine the hypothesis that switching to maintenance therapy with unboosted ATZ 400mg daily will have similar 48-week virologic efficacy to continuing ATZ/ritonavir 300/100mg daily among HIV-infected adults with stable viral load suppression on regimens comprising ATZ/ritonavir 300/100mg daily with TDF plus either FTC or 3TC, despite potentially lower ATZ trough levels with the unboosted regimen. In other words, patients whose HIV viral load is undetectable while receiving TDF (+FTC or 3TC) and ATZ/ritonavir will continue to maintain an undetectable viral load after switching to unboosted ATZ without ritonavir, in the same proportions as those continuing on their boosted ATZ/ritonavir regimen.
Detailed description
Following a screening visit to establish study eligibility, eligible consenting subjects will be randomized 1:1 to one of the two treatment arms (switch to unboosted ATZ or continue ritonavir-boosted ATZ). Randomized open-label treatment will commence following study procedures at baseline. Participants will be assessed at baseline and at weeks 4, 8, 12, 24, 36, and 48. On-study evaluations will include assessment of adverse clinical events and medication changes; blood tests for HIV viral load, CD4 cell count, standard safety parameters, fasting lipids and glucose, and pregnancy testing (if applicable); and urine tests for urinalysis and albumin to creatinine ratio. In addition, a serum sample will be stored at each visit for possible future testing. A timed plasma sample for measurement of pre-dose trough ATZ levels will be obtained once per subject at 4-8 weeks. Quality of life will be assessed by completion of the MOS-HIV questionnaire at baseline and every 12 weeks. Adherence will be assessed based on prescription refill data.
In case of protocol-defined virologic failure, a plasma sample for ATZ trough level will be collected, and genotypic resistance testing will be performed on plasma samples with viral load >250 copies/mL. Subjects with confirmed virologic failure will be asked to come to the clinic and will have their HIV treatment changed to a more effective regimen, selected based on the results of genotypic testing, as soon as possible.
The anticipated rate of confirmed virologic failure in the control arm is no more than 15% over the 48 weeks of the study. Once at least 20 subjects have been assigned to the experimental (switch) treatment arm, if the observed confirmed virologic failure rate in the experimental arm is greater than twice this rate, i.e. >30%, at any time during the study, the study will be stopped. At this time, subjects in the experimental arm will be reassessed as soon as possible and will resume ritonavir-boosted atazanavir or other effective HIV therapy as appropriate. The failure rate will be reassessed at a minimum after each 20 subjects are enrolled into the experimental (switch) arm.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Switch | Experimental | Drug: atazanavirswitch to unboosted atazanavir 400mg daily with the same nucleoside (NRTI) backbone |
| Continuation | Active comparator | Drug: atazanavir/ritonavircontinue on current regimen of atazanavir/ritonavir 300mg/100mg with the same nucleoside (NRTI) backbone |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- HIV infected adults at least 19 years of age
- Willing and able to provide informed consent to study participation
- Currently receiving a regimen including atazanavir 300mg/ritonavir 100mg daily with either tenofovir/emtricitabine (FTC) or tenofovir/lamivudine (3TC), for at least 3 months
- Plasma viral load (VL) <40 copies/mL for at least 2 consecutive measurements including the screening value, and < 150 copies/mL continuously for at least 3 months prior to screening
- Current regimen is first antiretroviral regimen, or if not first regimen, no evidence of resistance to any nucleosides (NRTIs) or protease inhibitors (PIs) on previous resistance tests
Key exclusion criteria (5 listed)
- Clinically significant intolerance or toxicity with current regimen precluding regimen continuation (e.g. intolerance/toxicity to ritonavir necessitating ritonavir discontinuation)
- pregnancy or breast-feeding
- antiretroviral regimen including any nonnucleoside reverse transcriptase inhibitor (nevirapine, efavirenz, or etravirine)
- antiretroviral regimen including any protease inhibitor other than atazanavir and ritonavir
- concomitant treatment with proton pump inhibitors, rifampin, St. John's wort, or garlic supplements. (Antacids and H2 receptor antagonists will be allowed provided their dosing is separated from atazanavir administration by at least 2 and 10 hours, respectively).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| atazanavirswitch to unboosted atazanavir 400 mg daily | Drug | Switch |
| atazanavir/ritonavirContinue current regimen of atazanavir 300 mg/ ritonavir 100 mg daily | Drug | Continuation |
Primary outcome
Proportions of Subjects Experiencing Virologic Failure by Randomized Treatment Arm
Time frame: at or before 48 weeks.
For the purposes of the study, virologic failure is defined as either regimen change for any reason, or plasma viral load >400 copies/mL on 2 consecutive measurements >2 weeks apart.
9 secondary outcomes
Proportions of Subjects in Each Randomized Treatment Arm With Atazanavir Trough Levels Below 150ng/mL
Time frame: 1 month (4-8 weeks)
Proportion of Subjects Experiencing Virologic Failure by Results of 1-month TDM
Time frame: at or before 48 weeks
Proportions of Subjects Experiencing Virologic Failure by Randomized Treatment Arm
Time frame: at or before 24 weeks.
Proportion of Subjects Experiencing Virologic Failure by Results of 1-month TDM
Time frame: at or before 24 weeks
CD4 Cell Count Changes (Absolute and Fraction)
Time frame: 24 and 48 weeks
Safety (Clinical and Laboratory Adverse Events)
Time frame: 24 and 48 weeks
Total Serum Bilirubin Levels
Time frame: 24 and 48 weeks
Metabolic Parameters
Time frame: 24 and 48 weeks
Quality of Life as Assessed by MOS-HIV
Time frame: 24 and 48 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 28067119Harris M, Ganase B, Watson B, Hull MW, Guillemi SA, Zhang W, Saeedi R, Harrigan PR. Efficacy and safety of "unboosting" atazanavir in a randomized controlled trial among HIV-infected patients receiving tenofovir DF. HIV Clin Trials. 2017 Jan;18(1):39-47. doi: 10.1080/15284336.2016.1271503. Epub 2017 Jan 9.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marianne Harris, MD principal investigator
Providence Health Care/ University of British Columbia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing atazanavir and atazanavir/ritonavir in people with HIV Infection, run by University of British Columbia at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Jul 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportions of Subjects Experiencing Virologic Failure by Randomized Treatment Arm (time frame: at or before 48 weeks.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01351740, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2018.