HIV/AIDSNCT03789968
The Incidence and Severity of Drug Interactions Before and After Switching Antiretroviral Therapy to Bictegravir/Emtricitabine/Tenofovir Alafenamide in Treatment Experienced Patients
An observational study of HIV/AIDS, run by Thomas Jefferson University at 1 site in United States.
Trial summary
This study will assess changes in the incidence and severity of drug interactions before and after switching antiretroviral therapy to bictegravir/emtricitabine/tenofovir alafenamide-based regimens in treatment experienced patients living with HIV infection. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- HIV/AIDS
- What is being tested?
- bictegravir/emtricitabine/tenofovir alafenamide
- How many people
- 411 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Sep 2019to 5 Oct 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
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 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Adults living with HIV infection and receiving antiretroviral therapy who have changed treatments to bictegravir/emtricitabine/tenofovir alafenamide
Who may be able to join
- HIV diagnosis
- 18 years of age or older
- Receiving ART for at least 3 months
- ART is switched to bictegravir/emtricitabine/tenofovir alafenamide between 2/7/2018 and 3/30/2019
- Patient is receiving at least one chronic or as needed non-ART medication at the time of the switch
Who cannot join
- -
Trial locations and contacts
1 site in 1 country.
United States1 site
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
About this study
This study will assess changes in the incidence and severity of drug interactions before and after switching antiretroviral therapy to bictegravir/emtricitabine/tenofovir alafenamide-based regimens in treatment experienced patients living with HIV infection.
Read the detailed description
Simple, safe and effective antiretroviral therapy (ART) can provide optimal treatment outcomes for people living with HIV infection (PLWH) [1]. Increasingly complex and poorly tolerated regimens, on the other hand often limit ART adherence, while drug-drug interactions (DDIs) and safety concerns with individual ART agents can limit treatment selection [2-4]. Fortunately, recent advances in ART have included the emergence of several highly effective, safe and well tolerated regimens with limited DDIs. In clinical trials, integrase strand transfer inhibitors (INSTIs) such as raltegravir, elvitegravir, dolutegravir and bictegravir are consistently as effective or more effective than comparator agents and often superior in terms of tolerability [5-10]. Due to their efficacy, safety, and tolerability, INSTI-based regimens are now routinely used in treatment naïve patients and emerging data suggests that several may be used to simplify therapy for selected patients with treatment experience [11, 12].
Among the INSTIs, bictegravir is the newest agent in the class [13]. Similar to dolutegravir and raltegravir and in contrast to elvitegravir, it has few significant drug-drug interactions. Unlike dolutegravir and raltegravir, bictegravir is available as part of a single-tablet, once-daily regimen that includes tenofovir alafenamide and emtricitabine (BIC/TAF/FTC). Raltegravir is not available within a single tablet regimen, while dolutegravir is available as part of a single-tablet regimen, but it includes abacavir, which has been linked to an increased cardiovascular disease risk. As a result, BIC/TAF/FTC is currently among the most effective, safe, well-tolerated treatment options with limited drug-drug interactions.
With several new treatment options available, particularly in the INSTI class, current guidelines advocate switching ART when possible in virologically suppressed, ART experienced patients [1]. Switching ART can simplify treatment, improve tolerability, eliminate toxicity, and mitigate drug-drug interactions. When switching ART for any reason, it is critical to review a patient's full HIV treatment history, including virologic responses, past ART-associated toxicities, and cumulative resistance before selecting a new regimen [1].
Drug-drug interaction assessments with a patient's concomitant medications should also be performed prior to switching ART. More than 70% of the HIV population will be above the age of 50 by the year 2020 and many are receiving 5 or more medications for common chronic conditions in addition to being ART experienced [14, 15]. Cardiovascular disease, hepatic and renal disease, osteoporosis, insulin resistance, metabolic disorders, and cancers are among the conditions that can occur more commonly in PLWH and at times earlier in life in comparison to their HIV negative counterparts [16]. Drug-drug interactions between medications needed to treat or prevent these comorbid conditions can often interact with ART. Switching ART, in many circumstances can reduce the number drug interactions with medications for comorbid conditions. Conversely, switching can also lead to new interactions requiring intervention to avoid toxicities or prevent ineffective treatment.
Multiple studies have confirmed that switching HIV treatment can improve patient adherence and quality of life [17]. Several studies have also confirmed that clinically significant drug-drug interactions are common in patients living with HIV, but none have assessed changes in the incidence and severity of drug-drug interactions in the setting of ART switches [18-20]. The primary objective of this study is to assess changes in the incidence and severity of drug interactions before and after switching ART to BIC/TAF/FTC -based regimens in treatment experienced patients.
Null Hypothesis:
There is no difference in the incidence and severity of drug-drug interactions between ART and concomitant medications before and after switching to a BIC/TAF/FTC-based ART regimen in treatment experienced patients.
Alternative Hypothesis:
The incidence and severity of drug-drug interactions between ART and concomitant medications is reduced after switching to a BIC/TAF/FTC-based ART regimen in treatment experienced patients.
Data Collection Subjects from the Jefferson Infectious Diseases Associates outpatient HIV Clinic will be evaluated for study inclusion. Co-investigators at six partner institutions will also evaluate patients at their HIV clinics for study inclusion. The following information will be collected for patients meeting the study criteria: age, gender, race, duration of HIV infection, duration of ART treatment, number of previous ART regimens, CD4+ cell count and HIV RNA directly prior to switching to a BIC/TAF/FTC-based ART regimen, and the reason for switching ART to a BIC/TAF/FTC-based regimen. Additionally, all concomitant medication names at the time of the ART switch will be collected.
Scoring System To assess the combined incidence and severity of drug interactions with concomitant medications (CM) prior to and following each patient's ART switch, a DDI incidence and severity score was developed. The score is based upon results obtained when entering medications into the University of Liverpool's HIV Drug Interaction Checker (ULHDIC) database [21]. Each ART-CM pair is given one of the following scores: "do not co-administer" is assigned a score of 2, "potential interaction" a score of 1, and "potential weak interaction" or "no interaction" a score of 0. For those interactions that have "no clear data," or for those medications that are not listed in the drug database, the Department of Health and Human Services HIV treatment guidelines will be consulted along with the FDA product labeling.
Score Validation A separate analysis (data not provided here) was completed by study investigators to validate the use of the ULDIC severity ranking. The medication profiles of a random, representative sample of the study's population were selected for analysis. Drug interaction scores using the aforementioned ULHDIC were compared with drug interaction scores determined manually using the Department of Health and Human Services HIV treatment guidelines and FDA product labeling. No statistical difference in drug interaction scores between methods was observed.
Primary Endpoint The primary endpoint of the study will be to measure the change in mean total drug interaction scores pre and post ART switch to a BIC/TAF/FTC-based ART regimen. The total drug interaction scores for each patient pre- and post-switch will be calculated. The average pre-switch and post-switch scores will then be determined and analyzed for statistical differences using a two-sided paired t-test (normal distribution) with an alpha level of 0.05 or a Wilcoxon Ranked Sum test (non-normal distribution).
Secondary Endpoints The secondary endpoint of the study will be to identify predictors of achieving drug interaction score reductions after switching to a BIC/TAF/FTC-based ART regimen. Predictors for achieving drug interaction score reductions will be examined using a multivariable linear regression model. Initial models will include all a priori determined variables and all variables will be examined for multi-collinearity. Models will be fit using a backwards selection procedure. Candidate predictors will be eliminated individually by comparing the log likelihood ratio test for each model step and using the 5% significance level.
- Conditions
- HIV/AIDS
- Being tested
- bictegravir/emtricitabine/tenofovir alafenamide
- Medical subject headings
- Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bictegravir/emtricitabine/tenofovir alafenamideDrug
Treatment experienced patients with HIV infection that switched to a bictegravir/emtricitabine/tenofovir alafenamide-based ART regimen
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in drug interactions after switching to bictegravir/emtricitabine/tenofovir alafenamide
The primary endpoint is to measure the change in mean total drug interaction scores pre and post ART switch to a bictegravir/emtricitabine/tenofovir alafenamide-based regimen. The total drug interaction scores for each patient pre- and post-switch will be calculated using a drug interaction score developed for this study. The score is obtained when entering a patient's ART and concomitant medications (CM) into the University of Liverpool's HIV Drug Interaction Checker database [21]. Each ART-CM pair is given one of the following scores: "do not co-administer" is a score of 2, "potential interaction" a score of 1, and "potential weak interaction" or "no interaction" a score of 0. When no interactions are observed between a patient's ART and CMs, the total score will be 0. Higher scores occur when interactions are present. A decrease in score indicates that switching to bictegravir/emtricitabine/tenofovir alafenamide decreased the number and severity of interactions present.
Measured: 1 year
Secondary outcomes (1)
Predictors of achieving drug interaction score reductions after switching to bictegravir/emtricitabine/tenofovir alafenamide
The secondary endpoint of the study is to identify predictors of drug interaction score reductions after switching to a bictegravir/emtricitabine/tenofovir alafenamide. Predictors will be examined using multivariable linear regression. Initial models will include all a priori variables which will be examined for multi-collinearity. Models will be fit using a backwards selection procedure. Candidate predictors will be eliminated individually by comparing the log likelihood ratio test for each model step and using the 5% significance level.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Dec 2018
- Study start1 Sep 2019
- Primary completion5 Sep 2020
- Study completion5 Oct 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (19)Papers the sponsor has linked to this study.
- Other trials for HIV/AIDSStudies of the same condition, open and under way.
- More trials run by Thomas Jefferson UniversityThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 411 participants (actual)
Sponsor and investigators
- Lead sponsor
- Thomas Jefferson University
- Sponsor type
- University, hospital or other
- Collaborators
- University of Maryland, College Park, Indiana University Health, The Brooklyn Hospital Center, University of Illinois Chicago, Nova Southeastern University, University of California, San Francisco
- Responsible party
- Principal investigator, Jason Schafer, Thomas Jefferson University
- Investigators
- Jason J Schafer, PharmD, MPH, Principal investigator, Thomas Jefferson University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03789968
- Sponsor's protocol ID
- 18G.786
- Status last verified
- Oct 2020
- First submitted
- 26 Dec 2018
- Last updated
- 8 Oct 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Saag MS, Benson CA, Gandhi RT, Hoy JF, Landovitz RJ, Mugavero MJ, Sax PE, Smith DM, Thompson MA, Buchbinder SP, Del Rio C, Eron JJ Jr, Fatkenheuer G, Gunthard HF, Molina JM, Jacobsen DM, Volberding PA. Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2018 Recommendations of the International Antiviral Society-USA Panel. JAMA. 2018 Jul 24;320(4):379-396. doi: 10.1001/jama.2018.8431.
PubMed 30043070Beer L, Skarbinski J. Adherence to antiretroviral therapy among HIV-infected adults in the United States. AIDS Educ Prev. 2014 Dec;26(6):521-37. doi: 10.1521/aeap.2014.26.6.521.
PubMed 25490733Pantuzza LL, Ceccato MDGB, Silveira MR, Junqueira LMR, Reis AMM. Association between medication regimen complexity and pharmacotherapy adherence: a systematic review. Eur J Clin Pharmacol. 2017 Nov;73(11):1475-1489. doi: 10.1007/s00228-017-2315-2. Epub 2017 Aug 4.
PubMed 28779460Yager J, Faragon J, McGuey L, Hoye-Simek A, Hecox Z, Sullivan S, Neubert S, Patel N. Relationship Between Single Tablet Antiretroviral Regimen and Adherence to Antiretroviral and Non-Antiretroviral Medications Among Veterans' Affairs Patients with Human Immunodeficiency Virus. AIDS Patient Care STDS. 2017 Sep;31(9):370-376. doi: 10.1089/apc.2017.0081. Epub 2017 Aug 3.
PubMed 28771023Lennox JL, DeJesus E, Lazzarin A, Pollard RB, Madruga JV, Berger DS, Zhao J, Xu X, Williams-Diaz A, Rodgers AJ, Barnard RJ, Miller MD, DiNubile MJ, Nguyen BY, Leavitt R, Sklar P; STARTMRK investigators. Safety and efficacy of raltegravir-based versus efavirenz-based combination therapy in treatment-naive patients with HIV-1 infection: a multicentre, double-blind randomised controlled trial. Lancet. 2009 Sep 5;374(9692):796-806. doi: 10.1016/S0140-6736(09)60918-1. Epub 2009 Aug 3.
PubMed 19647866DeJesus E, Rockstroh JK, Henry K, Molina JM, Gathe J, Ramanathan S, Wei X, Yale K, Szwarcberg J, White K, Cheng AK, Kearney BP; GS-236-0103 Study Team. Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate versus ritonavir-boosted atazanavir plus co-formulated emtricitabine and tenofovir disoproxil fumarate for initial treatment of HIV-1 infection: a randomised, double-blind, phase 3, non-inferiority trial. Lancet. 2012 Jun 30;379(9835):2429-2438. doi: 10.1016/S0140-6736(12)60918-0.
PubMed 22748590Sax PE, DeJesus E, Mills A, Zolopa A, Cohen C, Wohl D, Gallant JE, Liu HC, Zhong L, Yale K, White K, Kearney BP, Szwarcberg J, Quirk E, Cheng AK; GS-US-236-0102 study team. Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir versus co-formulated efavirenz, emtricitabine, and tenofovir for initial treatment of HIV-1 infection: a randomised, double-blind, phase 3 trial, analysis of results after 48 weeks. Lancet. 2012 Jun 30;379(9835):2439-2448. doi: 10.1016/S0140-6736(12)60917-9.
PubMed 22748591DeJesus E, Rockstroh JK, Lennox JL, Saag MS, Lazzarin A, Zhao J, Wan H, Rodgers AJ, Walker ML, Miller M, DiNubile MJ, Nguyen BY, Teppler H, Leavitt R, Sklar P; STARTMRK Investigators. Efficacy of raltegravir versus efavirenz when combined with tenofovir/emtricitabine in treatment-naive HIV-1-infected patients: week-192 overall and subgroup analyses from STARTMRK. HIV Clin Trials. 2012 Jul-Aug;13(4):228-32. doi: 10.1310/hct1304-228.
PubMed 22849964Raffi F, Jaeger H, Quiros-Roldan E, Albrecht H, Belonosova E, Gatell JM, Baril JG, Domingo P, Brennan C, Almond S, Min S; extended SPRING-2 Study Group. Once-daily dolutegravir versus twice-daily raltegravir in antiretroviral-naive adults with HIV-1 infection (SPRING-2 study): 96 week results from a randomised, double-blind, non-inferiority trial. Lancet Infect Dis. 2013 Nov;13(11):927-35. doi: 10.1016/S1473-3099(13)70257-3. Epub 2013 Sep 25.
PubMed 24074642Sax PE, Pozniak A, Montes ML, Koenig E, DeJesus E, Stellbrink HJ, Antinori A, Workowski K, Slim J, Reynes J, Garner W, Custodio J, White K, SenGupta D, Cheng A, Quirk E. Coformulated bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir with emtricitabine and tenofovir alafenamide, for initial treatment of HIV-1 infection (GS-US-380-1490): a randomised, double-blind, multicentre, phase 3, non-inferiority trial. Lancet. 2017 Nov 4;390(10107):2073-2082. doi: 10.1016/S0140-6736(17)32340-1. Epub 2017 Aug 31.
PubMed 28867499Arribas JR, Pialoux G, Gathe J, Di Perri G, Reynes J, Tebas P, Nguyen T, Ebrahimi R, White K, Piontkowsky D. Simplification to coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir versus continuation of ritonavir-boosted protease inhibitor with emtricitabine and tenofovir in adults with virologically suppressed HIV (STRATEGY-PI): 48 week results of a randomised, open-label, phase 3b, non-inferiority trial. Lancet Infect Dis. 2014 Jul;14(7):581-9. doi: 10.1016/S1473-3099(14)70782-0. Epub 2014 Jun 5.
PubMed 24908551Huhn GD, Tebas P, Gallant J, Wilkin T, Cheng A, Yan M, Zhong L, Callebaut C, Custodio JM, Fordyce MW, Das M, McCallister S. A Randomized, Open-Label Trial to Evaluate Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Plus Darunavir in Treatment-Experienced HIV-1-Infected Adults. J Acquir Immune Defic Syndr. 2017 Feb 1;74(2):193-200. doi: 10.1097/QAI.0000000000001193.
PubMed 27753684Tsiang M, Jones GS, Goldsmith J, Mulato A, Hansen D, Kan E, Tsai L, Bam RA, Stepan G, Stray KM, Niedziela-Majka A, Yant SR, Yu H, Kukolj G, Cihlar T, Lazerwith SE, White KL, Jin H. Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. Antimicrob Agents Chemother. 2016 Nov 21;60(12):7086-7097. doi: 10.1128/AAC.01474-16. Print 2016 Dec.
PubMed 27645238McNicholl IR, Gandhi M, Hare CB, Greene M, Pierluissi E. A Pharmacist-Led Program to Evaluate and Reduce Polypharmacy and Potentially Inappropriate Prescribing in Older HIV-Positive Patients. Pharmacotherapy. 2017 Dec;37(12):1498-1506. doi: 10.1002/phar.2043. Epub 2017 Nov 30.
PubMed 29023938Gallant J, Hsue PY, Shreay S, Meyer N. Comorbidities Among US Patients With Prevalent HIV Infection-A Trend Analysis. J Infect Dis. 2017 Dec 19;216(12):1525-1533. doi: 10.1093/infdis/jix518.
PubMed 29253205
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Incidence and Severity of Drug Interactions Before and After Switching Antiretroviral Therapy to Bictegravir/Emtricitabine/Tenofovir Alafenamide in Treatment Experienced Patients
- ClinicalTrials.gov ID
- NCT03789968
- Acronym / sponsor ID
- 18G.786
- Conditions
- HIV/AIDS
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 411 participants (actual)
- Lead sponsor
- Thomas Jefferson UniversityUniversity, hospital or other
- Collaborators
- University of Maryland, College Park, Indiana University Health, The Brooklyn Hospital Center, University of Illinois Chicago, Nova Southeastern University, University of California, San Francisco
- Study start
- 1 Sep 2019 (actual)
- Primary completion
- 5 Sep 2020 (actual)
- Study completion
- 5 Oct 2020 (actual)
- First posted
- 31 Dec 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will assess changes in the incidence and severity of drug interactions before and after switching antiretroviral therapy to bictegravir/emtricitabine/tenofovir alafenamide-based regimens in treatment experienced patients living with HIV infection.
Detailed description
Simple, safe and effective antiretroviral therapy (ART) can provide optimal treatment outcomes for people living with HIV infection (PLWH) [1]. Increasingly complex and poorly tolerated regimens, on the other hand often limit ART adherence, while drug-drug interactions (DDIs) and safety concerns with individual ART agents can limit treatment selection [2-4]. Fortunately, recent advances in ART have included the emergence of several highly effective, safe and well tolerated regimens with limited DDIs. In clinical trials, integrase strand transfer inhibitors (INSTIs) such as raltegravir, elvitegravir, dolutegravir and bictegravir are consistently as effective or more effective than comparator agents and often superior in terms of tolerability [5-10]. Due to their efficacy, safety, and tolerability, INSTI-based regimens are now routinely used in treatment naïve patients and emerging data suggests that several may be used to simplify therapy for selected patients with treatment experience [11, 12].
Among the INSTIs, bictegravir is the newest agent in the class [13]. Similar to dolutegravir and raltegravir and in contrast to elvitegravir, it has few significant drug-drug interactions. Unlike dolutegravir and raltegravir, bictegravir is available as part of a single-tablet, once-daily regimen that includes tenofovir alafenamide and emtricitabine (BIC/TAF/FTC). Raltegravir is not available within a single tablet regimen, while dolutegravir is available as part of a single-tablet regimen, but it includes abacavir, which has been linked to an increased cardiovascular disease risk. As a result, BIC/TAF/FTC is currently among the most effective, safe, well-tolerated treatment options with limited drug-drug interactions.
With several new treatment options available, particularly in the INSTI class, current guidelines advocate switching ART when possible in virologically suppressed, ART experienced patients [1]. Switching ART can simplify treatment, improve tolerability, eliminate toxicity, and mitigate drug-drug interactions. When switching ART for any reason, it is critical to review a patient's full HIV treatment history, including virologic responses, past ART-associated toxicities, and cumulative resistance before selecting a new regimen [1].
Drug-drug interaction assessments with a patient's concomitant medications should also be performed prior to switching ART. More than 70% of the HIV population will be above the age of 50 by the year 2020 and many are receiving 5 or more medications for common chronic conditions in addition to being ART experienced [14, 15]. Cardiovascular disease, hepatic and renal disease, osteoporosis, insulin resistance, metabolic disorders, and cancers are among the conditions that can occur more commonly in PLWH and at times earlier in life in comparison to their HIV negative counterparts [16]. Drug-drug interactions between medications needed to treat or prevent these comorbid conditions can often interact with ART. Switching ART, in many circumstances can reduce the number drug interactions with medications for comorbid conditions. Conversely, switching can also lead to new interactions requiring intervention to avoid toxicities or prevent ineffective treatment.
Multiple studies have confirmed that switching HIV treatment can improve patient adherence and quality of life [17]. Several studies have also confirmed that clinically significant drug-drug interactions are common in patients living with HIV, but none have assessed changes in the incidence and severity of drug-drug interactions in the setting of ART switches [18-20]. The primary objective of this study is to assess changes in the incidence and severity of drug interactions before and after switching ART to BIC/TAF/FTC -based regimens in treatment experienced patients.
Null Hypothesis:
There is no difference in the incidence and severity of drug-drug interactions between ART and concomitant medications before and after switching to a BIC/TAF/FTC-based ART regimen in treatment experienced patients.
Alternative Hypothesis:
The incidence and severity of drug-drug interactions between ART and concomitant medications is reduced after switching to a BIC/TAF/FTC-based ART regimen in treatment experienced patients.
Data Collection Subjects from the Jefferson Infectious Diseases Associates outpatient HIV Clinic will be evaluated for study inclusion. Co-investigators at six partner institutions will also evaluate patients at their HIV clinics for study inclusion. The following information will be collected for patients meeting the study criteria: age, gender, race, duration of HIV infection, duration of ART treatment, number of previous ART regimens, CD4+ cell count and HIV RNA directly prior to switching to a BIC/TAF/FTC-based ART regimen, and the reason for switching ART to a BIC/TAF/FTC-based regimen. Additionally, all concomitant medication names at the time of the ART switch will be collected.
Scoring System To assess the combined incidence and severity of drug interactions with concomitant medications (CM) prior to and following each patient's ART switch, a DDI incidence and severity score was developed. The score is based upon results obtained when entering medications into the University of Liverpool's HIV Drug Interaction Checker (ULHDIC) database [21]. Each ART-CM pair is given one of the following scores: "do not co-administer" is assigned a score of 2, "potential interaction" a score of 1, and "potential weak interaction" or "no interaction" a score of 0. For those interactions that have "no clear data," or for those medications that are not listed in the drug database, the Department of Health and Human Services HIV treatment guidelines will be consulted along with the FDA product labeling.
Score Validation A separate analysis (data not provided here) was completed by study investigators to validate the use of the ULDIC severity ranking. The medication profiles of a random, representative sample of the study's population were selected for analysis. Drug interaction scores using the aforementioned ULHDIC were compared with drug interaction scores determined manually using the Department of Health and Human Services HIV treatment guidelines and FDA product labeling. No statistical difference in drug interaction scores between methods was observed.
Primary Endpoint The primary endpoint of the study will be to measure the change in mean total drug interaction scores pre and post ART switch to a BIC/TAF/FTC-based ART regimen. The total drug interaction scores for each patient pre- and post-switch will be calculated. The average pre-switch and post-switch scores will then be determined and analyzed for statistical differences using a two-sided paired t-test (normal distribution) with an alpha level of 0.05 or a Wilcoxon Ranked Sum test (non-normal distribution).
Secondary Endpoints The secondary endpoint of the study will be to identify predictors of achieving drug interaction score reductions after switching to a BIC/TAF/FTC-based ART regimen. Predictors for achieving drug interaction score reductions will be examined using a multivariable linear regression model. Initial models will include all a priori determined variables and all variables will be examined for multi-collinearity. Models will be fit using a backwards selection procedure. Candidate predictors will be eliminated individually by comparing the log likelihood ratio test for each model step and using the 5% significance level.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Adults living with HIV infection and receiving antiretroviral therapy who have changed treatments to bictegravir/emtricitabine/tenofovir alafenamide
Key inclusion criteria (5 listed)
- HIV diagnosis
- 18 years of age or older
- Receiving ART for at least 3 months
- ART is switched to bictegravir/emtricitabine/tenofovir alafenamide between 2/7/2018 and 3/30/2019
- Patient is receiving at least one chronic or as needed non-ART medication at the time of the switch
Key exclusion criteria (1 listed)
- -
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 |
|---|---|---|
| bictegravir/emtricitabine/tenofovir alafenamideTreatment experienced patients with HIV infection that switched to a bictegravir/emtricitabine/tenofovir alafenamide-based ART regimen | Drug | – |
Primary outcome
Changes in drug interactions after switching to bictegravir/emtricitabine/tenofovir alafenamide
Time frame: 1 year
The primary endpoint is to measure the change in mean total drug interaction scores pre and post ART switch to a bictegravir/emtricitabine/tenofovir alafenamide-based regimen. The total drug interaction scores for each patient pre- and post-switch will be calculated using a drug interaction score developed for this study. The score is obtained when entering a patient's ART and concomitant medications (CM) into the University of Liverpool's HIV Drug Interaction Checker database [21]. Each ART-CM pair is given one of the following scores: "do not co-administer" is a score of 2, "potential interaction" a score of 1, and "potential weak interaction" or "no interaction" a score of 0. When no interactions are observed between a patient's ART and CMs, the total score will be 0. Higher scores occur when interactions are present. A decrease in score indicates that switching to bictegravir/emtricitabine/tenofovir alafenamide decreased the number and severity of interactions present.
1 secondary outcome
Predictors of achieving drug interaction score reductions after switching to bictegravir/emtricitabine/tenofovir alafenamide
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2020.
- Background: PubMed 30043070Saag MS, Benson CA, Gandhi RT, Hoy JF, Landovitz RJ, Mugavero MJ, Sax PE, Smith DM, Thompson MA, Buchbinder SP, Del Rio C, Eron JJ Jr, Fatkenheuer G, Gunthard HF, Molina JM, Jacobsen DM, Volberding PA. Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2018 Recommendations of the International Antiviral Society-USA Panel. JAMA. 2018 Jul 24;320(4):379-396. doi: 10.1001/jama.2018.8431.
- Background: PubMed 25490733Beer L, Skarbinski J. Adherence to antiretroviral therapy among HIV-infected adults in the United States. AIDS Educ Prev. 2014 Dec;26(6):521-37. doi: 10.1521/aeap.2014.26.6.521.
- Background: PubMed 28779460Pantuzza LL, Ceccato MDGB, Silveira MR, Junqueira LMR, Reis AMM. Association between medication regimen complexity and pharmacotherapy adherence: a systematic review. Eur J Clin Pharmacol. 2017 Nov;73(11):1475-1489. doi: 10.1007/s00228-017-2315-2. Epub 2017 Aug 4.
- Background: PubMed 28771023Yager J, Faragon J, McGuey L, Hoye-Simek A, Hecox Z, Sullivan S, Neubert S, Patel N. Relationship Between Single Tablet Antiretroviral Regimen and Adherence to Antiretroviral and Non-Antiretroviral Medications Among Veterans' Affairs Patients with Human Immunodeficiency Virus. AIDS Patient Care STDS. 2017 Sep;31(9):370-376. doi: 10.1089/apc.2017.0081. Epub 2017 Aug 3.
- Background: PubMed 19647866Lennox JL, DeJesus E, Lazzarin A, Pollard RB, Madruga JV, Berger DS, Zhao J, Xu X, Williams-Diaz A, Rodgers AJ, Barnard RJ, Miller MD, DiNubile MJ, Nguyen BY, Leavitt R, Sklar P; STARTMRK investigators. Safety and efficacy of raltegravir-based versus efavirenz-based combination therapy in treatment-naive patients with HIV-1 infection: a multicentre, double-blind randomised controlled trial. Lancet. 2009 Sep 5;374(9692):796-806. doi: 10.1016/S0140-6736(09)60918-1. Epub 2009 Aug 3.
- Background: PubMed 22748590DeJesus E, Rockstroh JK, Henry K, Molina JM, Gathe J, Ramanathan S, Wei X, Yale K, Szwarcberg J, White K, Cheng AK, Kearney BP; GS-236-0103 Study Team. Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate versus ritonavir-boosted atazanavir plus co-formulated emtricitabine and tenofovir disoproxil fumarate for initial treatment of HIV-1 infection: a randomised, double-blind, phase 3, non-inferiority trial. Lancet. 2012 Jun 30;379(9835):2429-2438. doi: 10.1016/S0140-6736(12)60918-0.
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- HIV Drug Interactions. University of Liverpool.Link provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Jason J Schafer, PharmD, MPH principal investigator
Thomas Jefferson University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of HIV/AIDS, run by Thomas Jefferson University at 1 site in United States.
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 5 inclusion and 1 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 8 Oct 2020. 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 United States. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Changes in drug interactions after switching to bictegravir/emtricitabine/tenofovir alafenamide (time frame: 1 year). 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 NCT03789968, which also lists 19 linked publications.
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 8 Oct 2020.