Switch to Unboosted Atazanavir With Tenofovir Study
Avainsanat
Abstrakti
Kuvaus
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.
Päivämäärät
| Viimeksi vahvistettu: | 09/30/2017 |
| Ensimmäinen lähetys: | 05/08/2011 |
| Arvioitu ilmoittautuminen lähetetty: | 05/09/2011 |
| Ensimmäinen lähetetty: | 05/10/2011 |
| Viimeisin päivitys lähetetty: | 10/23/2017 |
| Viimeisin päivitys lähetetty: | 07/29/2018 |
| Ensimmäisten tulosten toimittamispäivä: | 10/23/2017 |
| Ensimmäisten QC-tulosten toimittamispäivä: | 10/23/2017 |
| Ensimmäisten tulosten päivämäärä: | 07/29/2018 |
| Todellinen opintojen alkamispäivä: | 06/30/2011 |
| Arvioitu ensisijainen valmistumispäivä: | 12/31/2014 |
| Arvioitu tutkimuksen valmistumispäivä: | 11/30/2015 |
Ehto tai tauti
Interventio / hoito
Drug: Switch
Drug: Continuation
Vaihe
Varren ryhmät
| Varsi | Interventio / hoito |
|---|---|
| Experimental: Switch switch to unboosted atazanavir 400mg daily with the same nucleoside (NRTI) backbone | Drug: Switch switch to unboosted atazanavir 400 mg daily |
| Active Comparator: Continuation continue on current regimen of atazanavir/ritonavir 300mg/100mg with the same nucleoside (NRTI) backbone | Drug: Continuation Continue current regimen of atazanavir 300 mg/ ritonavir 100 mg daily |
Kelpoisuusehdot
| Tutkimukseen soveltuvat iät | 19 Years Vastaanottaja 19 Years |
| Sukupuolet, jotka ovat kelpoisia tutkimukseen | All |
| Hyväksyy terveelliset vapaaehtoiset | Joo |
| Kriteeri | Inclusion Criteria: 1. HIV infected adults at least 19 years of age 2. Willing and able to provide informed consent to study participation 3. Currently receiving a regimen including atazanavir 300mg/ritonavir 100mg daily with either tenofovir/emtricitabine (FTC) or tenofovir/lamivudine (3TC), for at least 3 months 4. 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 5. 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 6. Any CD4 Exclusion Criteria: 1. Clinically significant intolerance or toxicity with current regimen precluding regimen continuation (e.g. intolerance/toxicity to ritonavir necessitating ritonavir discontinuation) 2. pregnancy or breast-feeding 3. antiretroviral regimen including any nonnucleoside reverse transcriptase inhibitor (nevirapine, efavirenz, or etravirine) 4. antiretroviral regimen including any protease inhibitor other than atazanavir and ritonavir 5. 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). |
Tulokset
Ensisijaiset tulosmittaukset
1. Proportions of Subjects Experiencing Virologic Failure by Randomized Treatment Arm [at or before 48 weeks.]
Toissijaiset tulosmittaukset
1. Proportions of Subjects in Each Randomized Treatment Arm With Atazanavir Trough Levels Below 150ng/mL [1 month (4-8 weeks)]
2. Proportion of Subjects Experiencing Virologic Failure by Results of 1-month TDM [at or before 48 weeks]
3. Proportions of Subjects Experiencing Virologic Failure by Randomized Treatment Arm [at or before 24 weeks.]
4. Proportion of Subjects Experiencing Virologic Failure by Results of 1-month TDM [at or before 24 weeks]
5. CD4 Cell Count Changes (Absolute and Fraction) [24 and 48 weeks]
6. Safety (Clinical and Laboratory Adverse Events) [24 and 48 weeks]
7. Total Serum Bilirubin Levels [24 and 48 weeks]
8. Metabolic Parameters [24 and 48 weeks]
9. Quality of Life as Assessed by MOS-HIV [24 and 48 weeks]
