Effects of Ledipasvir/Sofosbuvir on the Pharmacokinetics and Renal Safety of Tenofovir Alafenamide (TAF)
Sponsor
University of Colorado, Denver (Other)
Overall Status
Completed
CT.gov ID
NCT03126370
Collaborator
(none)
10
1
1
20.7
0.5
Study Details
Study Description
Brief Summary
This study will evaluate the effect of ledipasvir/sofosbuvir (LDV/SOF) treatment on the pharmacokinetics (PK) and renal safety of tenofovir in the form of tenofovir alafenamide (TAF). Subjects living with human immunodeficiency virus (HIV) who are receiving tenofovir-based antiretroviral therapy (in the form of tenofovir disoproxil fumarate [TDF]), and are also taking a ritonavir- or cobicistat-boosted protease inhibitor will be invited to participate.
The study will consist of five visits: a screening visit, three abbreviated 4-hour pharmacokinetic visits, and one end-of-study follow-up visit.
Subjects will also be asked to use a Wisepill device, which will track medication adherence throughout the study.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
10 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Other
Official Title:
Effects of Ledipasvir/Sofosbuvir Treatment on the Pharmacokinetics and Renal Safety of Tenofovir Alafenamide (TAF) in Patients With HIV.
Actual Study Start Date
:
Jan 8, 2018
Actual Primary Completion Date
:
Jul 12, 2019
Actual Study Completion Date
:
Oct 1, 2019
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: TAF with a boosted PI and LDV/SOF Participants who are already taking tenofovir disoproxil fumarate 300 mg (in the form of Viread or Truvada) in combination with either a ritonavir- or cobicistat-boosted protease inhibitor for HIV treatment will continue to take their prescribed treatment for 12 weeks after enrollment. Participants will be switched from tenofovir disoproxil fumarate to tenofovir alafenamide (TAF) 25 mg/emtricitabine (FTC) 200 mg (Descovy) with a boosted protease inhibitor for the next 12 weeks. After taking TAF/FTC for 12 weeks, participants will then start taking ledipasvir 90mg/sofosbuvir 400mg (LDV/SOV, Harvoni) in combination with TAF/FTC and a boosted protease inhibitor for 4 weeks. Participants will then return to taking TAF/FTC with a boosted protease inhibitor for the final 12 weeks of the study. |
Drug: TDF with a boosted protease inhibitor
Participants who are already taking tenofovir disoproxil fumarate 300 mg (in the form of Viread or Truvada) in combination with either a ritonavir- or cobicistat-boosted protease inhibitor for HIV treatment will continue to take their prescribed treatment for 12 weeks after enrollment.
Other: Blood draws for tenofovir PK, renal function assessment
Other Names:
Drug: TAF with a boosted protease inhibitor
Participants will be switched from tenofovir disoproxil fumarate to tenofovir alafenamide 25 mg/emtricitabine 200 mg with a boosted protease inhibitor.
Other: Blood draws for tenofovir PK, renal function assessment
Other Names:
Drug: TAF with a boosted protease inhibitor and LDV/SOF
After taking tenofovir alafenamide/emtricitabine for 12 weeks, participants will then start taking ledipasvir 90 mg/sofosbuvir 400 mg (Harvoni) in combination with the tenofovir alafenamide 25 mg/emtricitabine 200 mg (Descovy) and a boosted protease inhibitor for 4 weeks. Subjects will then return to taking tenofovir alafenamide 25 mg/emtricitabine 200 mg (Descovy) and a boosted protease inhibitor for the final 12 weeks.
Other: Blood draws for tenofovir PK, renal function assessment
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Change From Week 12 Plasma Tenofovir Area Under the Plasma Concentration vs. Time Curve From Time 0 to 24 Hours (AUC0-24) at 24 and 28 Weeks [12 weeks and 24 weeks and 28 weeks]
Compare plasma tenofovir AUC0-24 between TAF with boosted PI vs. TDF with boosted PI (Phase 2 vs. 1), and between TAF with boosted PI and LDV/SOF vs. TDF with boosted PI (Phase 3 vs. 1)
- Change From Week 12 Tenofovir-diphosphate (TFV-DP) in Peripheral Blood Mononuclear Cells (PBMCs) at 24 and 28 Weeks [12 weeks, and 24 weeks and 28 weeks]
Compare tenofovir-diphosphate (TFV-DP) in peripheral blood mononuclear cells (PBMCs) between TAF with a boosted PI vs. TDF with a boosted PI (Phase 2 vs. 1), and TAF with a boosted PI and LDV/SOF vs. TDF with a boosted PI (Phase 3 vs. 1).
Secondary Outcome Measures
- Change From Week 12 Tenofovir-diphosphate (TFV-DP) in Dried Blood Spots (DBS) [12 weeks and 24 and 28 weeks]
Compare tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) between TAF with a boosted PI vs. TDF with a boosted PI (Phase 2 vs. 1), and TAF with a boosted PI and LDV/SOF vs. TDF with a boosted PI (Phase 3 vs. 1)
- Change in Estimated Glomerular Filtration Rate (eGFR) and Renal Biomarkers: eGFR [12 weeks, 24 weeks, and 28 weeks]
Change in estimated glomerular filtration rate (eGFR)
- Change in Estimated Glomerular Filtration Rate (eGFR) and Renal Biomarkers: UPCR [12 weeks, 24 weeks, and 28 weeks]
Change in estimated glomerular filtration rate (eGFR) and renal biomarkers: Urine protein to creatinine ratio (UPCR)
- Change in Estimated Glomerular Filtration Rate (eGFR) and Renal Biomarkers: B2M/Cr Ratio, and RBP/Cr Ratio [12 weeks, 24 weeks, and 28 weeks]
Change in renal biomarkers: urinary beta-2 microglobulin (B2M)/creatinine (Cr) ratio, and urinary retinol binding protein (RBP)/Cr ratio
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 70 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Between 18-70 years of age
-
Have been taking TDF and a ritonavir- or cobicistat-boosted protease inhibitor as part of standard care for treatment of HIV
Exclusion Criteria:
-
eGFR < 30 mL/min
-
Pregnant or planning pregnancy
-
Breastfeeding
-
Any medical, social, or mental-health issue(s) that, in the opinion of the investigators, could interfere with study participation or the study outcomes
-
Signs or symptoms of decompensated liver disease
-
Hepatitis B infection
-
Medications that may cause unwanted drug interactions with ledipasvir/sofosbuvir or emtricitabine/tenofovir alafenamide
-
Unwillingness or inability to comply with study procedures
-
Chronic hepatitis C infection
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Colorado Hospital | Aurora | Colorado | United States | 80045 |
Sponsors and Collaborators
- University of Colorado, Denver
Investigators
- Principal Investigator: Jennifer J Kiser, PharmD, University of Colorado, Denver
Study Documents (Full-Text)
More Information
Publications
- Afdhal N, Reddy KR, Nelson DR, Lawitz E, Gordon SC, Schiff E, Nahass R, Ghalib R, Gitlin N, Herring R, Lalezari J, Younes ZH, Pockros PJ, Di Bisceglie AM, Arora S, Subramanian GM, Zhu Y, Dvory-Sobol H, Yang JC, Pang PS, Symonds WT, McHutchison JG, Muir AJ, Sulkowski M, Kwo P; ION-2 Investigators. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. N Engl J Med. 2014 Apr 17;370(16):1483-93. doi: 10.1056/NEJMoa1316366. Epub 2014 Apr 11.
- Anderson PL, Glidden DV, Bushman LR, Heneine W, García-Lerma JG. Tenofovir diphosphate concentrations and prophylactic effect in a macaque model of rectal simian HIV transmission. J Antimicrob Chemother. 2014 Sep;69(9):2470-6. doi: 10.1093/jac/dku162. Epub 2014 May 26.
- Anderson PL, Glidden DV, Liu A, Buchbinder S, Lama JR, Guanira JV, McMahan V, Bushman LR, Casapía M, Montoya-Herrera O, Veloso VG, Mayer KH, Chariyalertsak S, Schechter M, Bekker LG, Kallás EG, Grant RM; iPrEx Study Team. Emtricitabine-tenofovir concentrations and pre-exposure prophylaxis efficacy in men who have sex with men. Sci Transl Med. 2012 Sep 12;4(151):151ra125.
- Anderson PL, Kiser JJ, Gardner EM, Rower JE, Meditz A, Grant RM. Pharmacological considerations for tenofovir and emtricitabine to prevent HIV infection. J Antimicrob Chemother. 2011 Feb;66(2):240-50. doi: 10.1093/jac/dkq447. Epub 2010 Nov 30. Review.
- Bushman LR, Kiser JJ, Rower JE, Klein B, Zheng JH, Ray ML, Anderson PL. Determination of nucleoside analog mono-, di-, and tri-phosphates in cellular matrix by solid phase extraction and ultra-sensitive LC-MS/MS detection. J Pharm Biomed Anal. 2011 Sep 10;56(2):390-401. doi: 10.1016/j.jpba.2011.05.039. Epub 2011 Jun 6.
- Castillo-Mancilla J, Coyle R, Zheng J, al e. Tenofovir Diphosphate Arising from TAF is Quantifiable in Dried Blood Spots. Conference on Retroviruses and Opportunistic Infections. Seattle Washington, February 13-16, 2017.
- Cope R PA, Glowa T, Faulds S, Veldkamp P, Prasad R. Majority of HIV/HCV Co-infected Patients Require Antiretroviral Therapy Switch Prior to Use of Simeprevir (abstract 651). CROI 2015; February 23-26, 2015. Seattle, WA.
- Garrison K ea. Drug Interactions between anti-HCV Antivirals Ledipasvir/Sofosbuvir and Integrase Strand Transfer Inhibitor-Based Regimens. 16th International Workshop on Clinical Pharmacology of HIV and Hepatitis Therapy, Washington DC. May 26-28, 2015, abstrac #71
- Genovese D, Boesecke C, Coppola N, Vella S. Virus Variability and Its Impact on HIV and Hepatitis Therapy. Adv Virol. 2012;2012:607527. doi: 10.1155/2012/607527. Epub 2012 Dec 27.
- German P GK, Pang PS, et al. Drug Interactions Between the anti-HCV Regimen Ledipasvir/Sofosbuvir and Ritonavir-Boosted Protease Inhibitors plus Emtricitabine/Tenofovir DF. CROI 2015; February 23-26, 2015; Seattle WA.
- Hall AM, Hendry BM, Nitsch D, Connolly JO. Tenofovir-associated kidney toxicity in HIV-infected patients: a review of the evidence. Am J Kidney Dis. 2011 May;57(5):773-80. doi: 10.1053/j.ajkd.2011.01.022. Epub 2011 Mar 23. Review.
- Havens PL, Kiser JJ, Stephensen CB, Hazra R, Flynn PM, Wilson CM, Rutledge B, Bethel J, Pan CG, Woodhouse LR, Van Loan MD, Liu N, Lujan-Zilbermann J, Baker A, Kapogiannis BG, Gordon CM, Mulligan K; Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) 063 Study Team. Association of higher plasma vitamin D binding protein and lower free calcitriol levels with tenofovir disoproxil fumarate use and plasma and intracellular tenofovir pharmacokinetics: cause of a functional vitamin D deficiency? Antimicrob Agents Chemother. 2013 Nov;57(11):5619-28. doi: 10.1128/AAC.01096-13. Epub 2013 Sep 3.
- Höner Zu Siederdissen C, Maasoumy B, Marra F, Deterding K, Port K, Manns MP, Cornberg M, Back D, Wedemeyer H. Drug-Drug Interactions With Novel All Oral Interferon-Free Antiviral Agents in a Large Real-World Cohort. Clin Infect Dis. 2016 Mar 1;62(5):561-7. doi: 10.1093/cid/civ973. Epub 2015 Nov 26.
- Kiser JJ, Aquilante CL, Anderson PL, King TM, Carten ML, Fletcher CV. Clinical and genetic determinants of intracellular tenofovir diphosphate concentrations in HIV-infected patients. J Acquir Immune Defic Syndr. 2008 Mar 1;47(3):298-303.
- Kiser JJ, Carten ML, Aquilante CL, Anderson PL, Wolfe P, King TM, Delahunty T, Bushman LR, Fletcher CV. The effect of lopinavir/ritonavir on the renal clearance of tenofovir in HIV-infected patients. Clin Pharmacol Ther. 2008 Feb;83(2):265-72. Epub 2007 Jun 27.
- Kiser JJ, Fletcher CV, Flynn PM, Cunningham CK, Wilson CM, Kapogiannis BG, Major-Wilson H, Viani RM, Liu NX, Muenz LR, Harris DR, Havens PL; Adolescent Trials Network for HIV/AIDS Interventions. Pharmacokinetics of antiretroviral regimens containing tenofovir disoproxil fumarate and atazanavir-ritonavir in adolescents and young adults with human immunodeficiency virus infection. Antimicrob Agents Chemother. 2008 Feb;52(2):631-7. Epub 2007 Nov 19.
- Langness J LB, Rogers M, J. KJ. Readying HIV/HCV Coinfected Patients for HCV Treatment: Occurrence and Management of Antiviral Interactions (abstract 18). 16th International Workshop on Clinical Pharmacology of HIV and Hepatitis Therapy; May 26-28, 2015; Washington, DC.
- MacBrayne CE MK, Fierer DS, et al. Increase Tenofovir Diphosphate in Red Blood Cells, but Not Tenofovir in Plasma, with Sofosbuvir and Ribavirin. 17th International Workshop on Clinical Pharmacology of HIV and Hepatitis Therapy; Washington DC, June 2016 Accepted Abstract (Oral).
- MacBrayne CE, Kiser JJ. Pharmacologic Considerations in the Treatment of Hepatitis C Virus in Persons With HIV. Clin Infect Dis. 2016 Jul 15;63 Suppl 1:S12-23. doi: 10.1093/cid/ciw220. Review. Erratum in: Clin Infect Dis. 2016 Sep 1;63(5):715.
- Monteiro N, Branco M, Peres S, Borges F, Mansinho K. The impact of tenofovir disoproxil fumarate on kidney function: four-year data from the HIV-infected outpatient cohort. J Int AIDS Soc. 2014 Nov 2;17(4 Suppl 3):19565. doi: 10.7448/IAS.17.4.19565. eCollection 2014.
- Moss DM, Neary M, Owen A. The role of drug transporters in the kidney: lessons from tenofovir. Front Pharmacol. 2014 Nov 11;5:248. doi: 10.3389/fphar.2014.00248. eCollection 2014. Review. Erratum in: Front Pharmacol. 2015;6:18.
- Naggie S, Cooper C, Saag M, Workowski K, Ruane P, Towner WJ, Marks K, Luetkemeyer A, Baden RP, Sax PE, Gane E, Santana-Bagur J, Stamm LM, Yang JC, German P, Dvory-Sobol H, Ni L, Pang PS, McHutchison JG, Stedman CA, Morales-Ramirez JO, Bräu N, Jayaweera D, Colson AE, Tebas P, Wong DK, Dieterich D, Sulkowski M; ION-4 Investigators. Ledipasvir and Sofosbuvir for HCV in Patients Coinfected with HIV-1. N Engl J Med. 2015 Aug 20;373(8):705-13. doi: 10.1056/NEJMoa1501315. Epub 2015 Jul 21.
- Ruane PJ, DeJesus E, Berger D, Markowitz M, Bredeek UF, Callebaut C, Zhong L, Ramanathan S, Rhee MS, Fordyce MW, Yale K. Antiviral activity, safety, and pharmacokinetics/pharmacodynamics of tenofovir alafenamide as 10-day monotherapy in HIV-1-positive adults. J Acquir Immune Defic Syndr. 2013 Aug 1;63(4):449-55. doi: 10.1097/QAI.0b013e3182965d45.
- Sax PE, Zolopa A, Brar I, Elion R, Ortiz R, Post F, Wang H, Callebaut C, Martin H, Fordyce MW, McCallister S. Tenofovir alafenamide vs. tenofovir disoproxil fumarate in single tablet regimens for initial HIV-1 therapy: a randomized phase 2 study. J Acquir Immune Defic Syndr. 2014 Sep 1;67(1):52-8. doi: 10.1097/QAI.0000000000000225.
- Sulkowski MS. Hepatitis C virus-human immunodeficiency virus coinfection. Liver Int. 2012 Feb;32 Suppl 1:129-34. doi: 10.1111/j.1478-3231.2011.02719.x. Review.
- Tourret J, Deray G, Isnard-Bagnis C. Tenofovir effect on the kidneys of HIV-infected patients: a double-edged sword? J Am Soc Nephrol. 2013 Oct;24(10):1519-27. doi: 10.1681/ASN.2012080857. Epub 2013 Sep 19. Review.
Responsible Party:
University of Colorado, Denver
ClinicalTrials.gov Identifier:
NCT03126370
Other Study ID Numbers:
- 17-0490
First Posted:
Apr 24, 2017
Last Update Posted:
Feb 11, 2021
Last Verified:
Jan 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Product Manufactured in and Exported from the U.S.:
No
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | TAF With a Boosted PI and LDV/SOF |
|---|---|
| Arm/Group Description | Subjects who are already taking tenofovir disoproxil fumarate 300 mg (in the form of Viread or Truvada) in combination with either a ritonavir- or cobicistat-boosted protease inhibitor for HIV treatment will continue to take their prescribed treatment for 12 weeks after enrollment. Subjects will be switched from tenofovir disoproxil fumarate to tenofovir alafenamide (TAF) 25 mg/emtricitabine (FTC) 200 mg (Descovy) with a boosted protease inhibitor for the next 12 weeks. After taking TAF/FTC for 12 weeks, subjects will then start taking ledipasvir 90mg/sofosbuvir 400mg (Harvoni) in combination with TAF/FTC and a boosted protease inhibitor for 4 weeks. Subjects will then return to taking TAF/FTC with a boosted protease inhibitor for the final 12 weeks of the study. TDF with a boosted protease inhibitor: Subjects who are already taking tenofovir disoproxil fumarate 300 mg (in the form of Viread or Truvada) in combination with either a ritonavir- or cobicistat-boosted protease |
| Period Title: TDF With a Boosted PI | |
| STARTED | 10 |
| COMPLETED | 10 |
| NOT COMPLETED | 0 |
| Period Title: TDF With a Boosted PI | |
| STARTED | 10 |
| COMPLETED | 10 |
| NOT COMPLETED | 0 |
| Period Title: TDF With a Boosted PI | |
| STARTED | 10 |
| COMPLETED | 10 |
| NOT COMPLETED | 0 |
| Period Title: TDF With a Boosted PI | |
| STARTED | 10 |
| COMPLETED | 10 |
| NOT COMPLETED | 0 |
Baseline Characteristics
| Arm/Group Title | TAF With a Boosted PI and LDV/SOF |
|---|---|
| Arm/Group Description | Subjects who are already taking tenofovir disoproxil fumarate 300 mg (in the form of Viread or Truvada) in combination with either a ritonavir- or cobicistat-boosted protease inhibitor for HIV treatment will continue to take their prescribed treatment for 12 weeks after enrollment. Subjects will be switched from tenofovir disoproxil fumarate to tenofovir alafenamide (TAF) 25 mg/emtricitabine (FTC) 200 mg (Descovy) with a boosted protease inhibitor for the next 12 weeks. After taking TAF/FTC for 12 weeks, subjects will then start taking ledipasvir 90mg/sofosbuvir 400mg (Harvoni) in combination with TAF/FTC and a boosted protease inhibitor for 4 weeks. Subjects will then return to taking TAF/FTC with a boosted protease inhibitor for the final 12 weeks of the study. TDF with a boosted protease inhibitor: Subjects who are already taking tenofovir disoproxil fumarate 300 mg (in the form of Viread or Truvada) in combination with either a ritonavir- or cobicistat-boosted protease |
| Overall Participants | 10 |
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
50
(12.3)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
1
10%
|
| Male |
9
90%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |
| Hispanic or Latino |
5
50%
|
| Not Hispanic or Latino |
5
50%
|
| Unknown or Not Reported |
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
1
10%
|
| White |
9
90%
|
| More than one race |
0
0%
|
| Unknown or Not Reported |
0
0%
|
| Region of Enrollment (participants) [Number] | |
| United States |
10
100%
|
| eGFR (mL/min/1.73^m2) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [mL/min/1.73^m2] |
91.5
(26.6)
|
| Weight (kg) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [kg] |
88.8
(16.6)
|
Outcome Measures
| Title | Change From Week 12 Plasma Tenofovir Area Under the Plasma Concentration vs. Time Curve From Time 0 to 24 Hours (AUC0-24) at 24 and 28 Weeks |
|---|---|
| Description | Compare plasma tenofovir AUC0-24 between TAF with boosted PI vs. TDF with boosted PI (Phase 2 vs. 1), and between TAF with boosted PI and LDV/SOF vs. TDF with boosted PI (Phase 3 vs. 1) |
| Time Frame | 12 weeks and 24 weeks and 28 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | TDF With a Boosted PI | TAF With a Boosted PI | TAF With a Boosted PI and LDV/SOF |
|---|---|---|---|
| Arm/Group Description | Tenofovir disoproxil fumarate with a boosted protease inhibitor | Tenofovir alafenamide with a boosted protease inhibitor | Tenofovir alafenamide with a boosted protease inhibitor and ledipasvir/sofosbuvir |
| Measure Participants | 10 | 10 | 10 |
| Geometric Mean (Geometric Coefficient of Variation) [ng*h/mL] |
3466
(51.4)
|
743
(35.8)
|
868
(40.8)
|
| Title | Change From Week 12 Tenofovir-diphosphate (TFV-DP) in Peripheral Blood Mononuclear Cells (PBMCs) at 24 and 28 Weeks |
|---|---|
| Description | Compare tenofovir-diphosphate (TFV-DP) in peripheral blood mononuclear cells (PBMCs) between TAF with a boosted PI vs. TDF with a boosted PI (Phase 2 vs. 1), and TAF with a boosted PI and LDV/SOF vs. TDF with a boosted PI (Phase 3 vs. 1). |
| Time Frame | 12 weeks, and 24 weeks and 28 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | TDF With a Boosted PI | TAF With a Boosted PI | TAF With a Boosted PI and LDV/SOF |
|---|---|---|---|
| Arm/Group Description | Tenofovir disoproxil fumarate with a boosted protease inhibitor | Tenofovir alafenamide with a boosted protease inhibitor | Tenofovir alafenamide with a boosted protease inhibitor and ledipasvir/sofosbuvir |
| Measure Participants | 10 | 10 | 10 |
| Geometric Mean (Geometric Coefficient of Variation) [fmol/10^6 cells] |
83.0
(66.6)
|
926
(23.4)
|
1129
(34.9)
|
| Title | Change From Week 12 Tenofovir-diphosphate (TFV-DP) in Dried Blood Spots (DBS) |
|---|---|
| Description | Compare tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) between TAF with a boosted PI vs. TDF with a boosted PI (Phase 2 vs. 1), and TAF with a boosted PI and LDV/SOF vs. TDF with a boosted PI (Phase 3 vs. 1) |
| Time Frame | 12 weeks and 24 and 28 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Comparisons between study phases were controlled for 3-month adherence. Results reported |
| Arm/Group Title | TDF With a Boosted PI | TAF With a Boosted PI | TAF With a Boosted PI and LDV/SOF |
|---|---|---|---|
| Arm/Group Description | Tenofovir disoproxil fumarate with a boosted protease inhibitor | Tenofovir alafenamide with a boosted protease inhibitor | Tenofovir alafenamide with a boosted protease inhibitor and ledipasvir/sofosbuvir |
| Measure Participants | 10 | 10 | 10 |
| Geometric Mean (Geometric Coefficient of Variation) [fmol/2x7mm punches] |
36014
(46.4)
|
6735
(45.0)
|
6100
(41.0)
|
| Title | Change in Estimated Glomerular Filtration Rate (eGFR) and Renal Biomarkers: eGFR |
|---|---|
| Description | Change in estimated glomerular filtration rate (eGFR) |
| Time Frame | 12 weeks, 24 weeks, and 28 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | TDF With a Boosted PI | TAF With a Boosted PI | TAF With a Boosted PI and LDV/SOF |
|---|---|---|---|
| Arm/Group Description | Tenofovir disoproxil fumarate with a boosted protease inhibitor | Tenofovir alafenamide with a boosted protease inhibitor | Tenofovir alafenamide with a boosted protease inhibitor and ledipasvir/sofosbuvir |
| Measure Participants | 10 | 10 | 10 |
| Geometric Mean (Geometric Coefficient of Variation) [mL/min/1.73 m^2] |
86.7
(27.6)
|
91.0
(23.0)
|
88.1
(24.9)
|
| Title | Change in Estimated Glomerular Filtration Rate (eGFR) and Renal Biomarkers: UPCR |
|---|---|
| Description | Change in estimated glomerular filtration rate (eGFR) and renal biomarkers: Urine protein to creatinine ratio (UPCR) |
| Time Frame | 12 weeks, 24 weeks, and 28 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | TDF With a Boosted PI | TAF With a Boosted PI | TAF With a Boosted PI and LDV/SOF |
|---|---|---|---|
| Arm/Group Description | Tenofovir disoproxil fumarate with a boosted protease inhibitor | Tenofovir alafenamide with a boosted protease inhibitor | Tenofovir alafenamide with a boosted protease inhibitor and ledipasvir/sofosbuvir |
| Measure Participants | 10 | 10 | 10 |
| Geometric Mean (Geometric Coefficient of Variation) [mg/g] |
134
(65.7)
|
118
(50.2)
|
97.3
(41.0)
|
| Title | Change in Estimated Glomerular Filtration Rate (eGFR) and Renal Biomarkers: B2M/Cr Ratio, and RBP/Cr Ratio |
|---|---|
| Description | Change in renal biomarkers: urinary beta-2 microglobulin (B2M)/creatinine (Cr) ratio, and urinary retinol binding protein (RBP)/Cr ratio |
| Time Frame | 12 weeks, 24 weeks, and 28 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | TDF With a Boosted PI | TAF With a Boosted PI | TAF With a Boosted PI and LDV/SOF |
|---|---|---|---|
| Arm/Group Description | Tenofovir disoproxil fumarate with a boosted protease inhibitor | Tenofovir alafenamide with a boosted protease inhibitor | Tenofovir alafenamide with a boosted protease inhibitor and ledipasvir/sofosbuvir |
| Measure Participants | 10 | 10 | 10 |
| β2M:Cr ratio |
419
(176)
|
224
(167)
|
178
(156)
|
| RBP:Cr ratio |
436
(174)
|
242
(180)
|
146
(91.6)
|
Adverse Events
| Time Frame | 40 weeks | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Adverse events were graded according to the Division of AIDS AE Reporting Table (July 2017, version 2.1) | |||||
| Arm/Group Title | TDF With a Boosted PI | TAF With a Boosted PI | TAF With a Boosted PI and LDV/SOF | |||
| Arm/Group Description | Tenofovir disoproxil fumarate with a boosted protease inhibitor | Tenofovir alafenamide with a boosted protease inhibitor | Tenofovir alafenamide with a boosted protease inhibitor and ledipasvir/sofosbuvir | |||
All Cause Mortality |
||||||
| TDF With a Boosted PI | TAF With a Boosted PI | TAF With a Boosted PI and LDV/SOF | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/10 (0%) | 0/10 (0%) | 0/10 (0%) | |||
Serious Adverse Events |
||||||
| TDF With a Boosted PI | TAF With a Boosted PI | TAF With a Boosted PI and LDV/SOF | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/10 (0%) | 0/10 (0%) | 0/10 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| TDF With a Boosted PI | TAF With a Boosted PI | TAF With a Boosted PI and LDV/SOF | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/10 (20%) | 2/10 (20%) | 1/10 (10%) | |||
| Renal and urinary disorders | ||||||
| Renal events deemed possibly, probably or related | 2/10 (20%) | 3 | 2/10 (20%) | 3 | 1/10 (10%) | 1 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Jennifer Kiser, PharmD, PhD |
|---|---|
| Organization | University of Colorado Anschutz Medical Campus |
| Phone | 3037246131 |
| jennifer.kiser@cuanschutz.edu |
Responsible Party:
University of Colorado, Denver
ClinicalTrials.gov Identifier:
NCT03126370
Other Study ID Numbers:
- 17-0490
First Posted:
Apr 24, 2017
Last Update Posted:
Feb 11, 2021
Last Verified:
Jan 1, 2021