Switch to Unboosted Atazanavir With Tenofovir Study

NCT01351740 | Completed Phase 4 Results DMC

• 1 other identifier: H10-03255
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

HIV Infection

Keywords

HIV; Anti-HIV Agents; HIV Protease Inhibitors

Outcome Measures

Primary Outcomes (1)

• 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.

  at or before 48 weeks.

Secondary Outcomes (9)

• Proportions of Subjects in Each Randomized Treatment Arm With Atazanavir Trough Levels Below 150ng/mL

  1 month (4-8 weeks)

• Proportion of Subjects Experiencing Virologic Failure by Results of 1-month TDM

  at or before 48 weeks

• Proportions of Subjects Experiencing Virologic Failure by Randomized Treatment Arm

  at or before 24 weeks.

• Proportion of Subjects Experiencing Virologic Failure by Results of 1-month TDM

  at or before 24 weeks

• CD4 Cell Count Changes (Absolute and Fraction)

  24 and 48 weeks

Study Arms (2)

Switch

EXPERIMENTAL

switch to unboosted atazanavir 400mg daily with the same nucleoside (NRTI) backbone

Drug: atazanavir

Continuation

ACTIVE COMPARATOR

continue on current regimen of atazanavir/ritonavir 300mg/100mg with the same nucleoside (NRTI) backbone

Drug: atazanavir/ritonavir

Interventions

atazanavir DRUG

switch to unboosted atazanavir 400 mg daily

Switch

atazanavir/ritonavir DRUG

Continue current regimen of atazanavir 300 mg/ ritonavir 100 mg daily

Continuation

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• University of British Columbia: lead

Study Sites (1)

Immunodeficiency Clinic, St. Paul's Hospital

Vancouver, British Columbia, V6Z1Y6, Canada

Location

Related Publications (1)

• 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.

  PMID: 28067119 RESULT

MeSH Terms

Conditions

HIV Infections

Interventions

Atazanavir Sulfate; atazanavir, ritonavir drug combination

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Dr Marianne Harris
• Organization: British Columbia Centre for Excellence in HIV/AIDS

mharris@cfenet.ubc.ca

1-604-806-8771

Study Officials

• Marianne Harris, MD

  Providence Health Care/ University of British Columbia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr. Marianne Harris

Study Record Dates

• First Submitted: May 9, 2011
• First Posted: May 11, 2011
• Study Start: July 1, 2011
• Primary Completion: January 1, 2015
• Study Completion: December 1, 2015
• Last Updated: July 30, 2018
• Results First Posted: July 30, 2018

Record last verified: 2017-10

Locations

CA (1)