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Bictegravir in the Elderly Living With HIV (BICEP)

Sponsor
State University of New York at Buffalo (Other)
Overall Status
Recruiting
CT.gov ID
NCT05064020
Collaborator
Gilead Sciences (Industry)
160
Enrollment
1
Location
35.9
Anticipated Duration (Months)
4.5
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a prospective, open-label, single center, post-approval and post-marketing study. Current national guideline recommends an integrase strand inhibitors (INSTI) in combination with two nucleoside reverse transcriptase inhibitors (NRTIs) as standard of therapy for HIV-1 infected patients. INSTI-based regimen may require a potent CYP3A inhibitor such as cobicistat to increase INSTI's plasma concentration and prolongs half-life. However, co-administration with a CYP3A inhibitor may increase the risk of drug-drug interactions. A novel INSTI, bictegravir, does not need a booster for pharmacokinetic enhancement.

Hypothesis: switching HIV-1 infected patients from booster containing regimen to bictegravir based regimen would decrease the risk of drug-drug interactions caused by a booster and improve quality of life and adherence.

Condition or Disease Intervention/Treatment Phase
  • Drug: Bictegravir/Emtricitabine/Tenofovir Alafenamide 50 MG-200 MG-25 MG Oral Tablet [BIKTARVY]

Detailed Description

Antiretroviral treatment consisting of integrase strand inhibitors (INSTI) in combination with two nucleoside reverse transcriptase inhibitors (NRTIs) has become the standard of therapy for HIV-1 infected patients (2017 DHHS Guidelines). The development and advancement of such therapy have resulted in improved prognosis, allowing a larger proportion of patients in United States (> 50%) with HIV-1 infection to be 50 years of age or older, which is defined by the CDC as "older adults". A novel INSTI, bictegravir (BIC), has been recently approved by FDA, available in a fixed dose combination with emtricitabine (FTC) and tenofovir alafenamide (TAF) as a novel single-tablet regimen (STR), BIKTARVY®. Similar to other INSTI, BIC prevents HIV replication by inhibiting HIV integration into the host cell. In vitro studies have shown its selectivity against HIV-1 infected cells with a low cytotoxic profile.

Elvitegravir, boosted with cobicistat, is currently available as part of a single-tablet formulation with FTC and TAF (GenvoyaTM) or with FTC and TDF (StribildTM). Unlike ritonavir, cobicistat has no antiretroviral activity, but has potent inhibitory effects on CYP3A44. Elvitegravir is primarily metabolized by CYP3A4 and its co-administration with cobicistat boosts elvitegravir plasma concentration and prolongs its half-life4. Concurrent use of a potent CYP3A4 inhibitor, e.g., cobicistat, with medications that are metabolized by CYP3A4 can significantly increase the risk of drug-drug interactions. With an increase in the average survivability age of HIV-infected patients, chances of polypharmacy due to multimorbidity, a term used to define the presence of two or more concurrent chronic medical conditions, increases. Two studies have demonstrated that older HIV+ individuals engaged in polypharmacy are more likely to experience potential drug-drug interactions (PDDI). Many chronic medications such as antidepressants, HMG-CoA reductase inhibitors (statins), and cardiovascular medications are metabolized by CYP3A4. Concurrent administration of these medications with GenvoyaTM and StribildTMcan lead to increases in PDDI. Such interactions can result in more adverse drug reactions, drug-related toxicity of narrow therapeutic index drugs, and variations in the efficacy of concurrent medications. However, unlike elvitegravir, BIC does not require a booster such as cobicistat for pharmacokinetic enhancement. Its use can result in reductions in PDDI caused by cobicistat in adults with polypharmacy. This can improve quality of life in general, adherence and can directly avoid DDI-related adverse effects.

Although antiretroviral therapy (ART), when used concurrently with certain medications, has an increased risk of PDDI, studies have suggested a low DDI profile of BIC. In this study, such benefits of bictegravir will be assessed through the evaluation of polypharmacy, PDDI, health-related quality of life, and adherence of HIV-infected subjects.

BIC/FTC/TAF related adverse drug events are possible in the study. Due to BIC's recent FDA approval, a comprehensive list on the possible adverse drug events has become available. Common side effects reported in clinical phase II and phase III studies include diarrhea, nausea, and headache. Serious adverse events, including lactic acidosis, severe hepatomegaly have been reported with nucleoside reverse transcriptase inhibitors, but are uncommon. The standard regimen of BIC/FTC/TAF will be used; if a regimen change occurs, participation in the study will be discontinued. Participants will be carefully screened and those with pre-conditions, such as morbid obesity, hepatitis B virus, hepatitis C virus co-infection will be documented in the study.

Study Design

Study Type:
Observational
Anticipated Enrollment :
160 participants
Observational Model:
Case-Control
Time Perspective:
Prospective
Official Title:
Bictegravir in the Elderly Living With HIV: Impact of Polypharmacy and Multimorbidity (BICEP)
Actual Study Start Date :
Aug 1, 2020
Anticipated Primary Completion Date :
Jul 31, 2022
Anticipated Study Completion Date :
Jul 31, 2023

Arms and Interventions

Arm Intervention/Treatment
Polypharmacy

Polypharmacy: patient is using five or more medications will be considered polypharmacy. Subjects having polypharmacy condition with taking Elvitegravir/Cobicistat/Emtricitabine/Tenofovir/Alafenamide 150MG-150MG-200MG-10MG Oral Tablet [Genvoya] or Elevitegravir/Cobicistat/Emtricitabine/Tenofovir disoproxil fumarate 150MG-150MG-200MG-300MG Oral Tablet [Stribild] will switch to Bictegravir/Emtricitabine/Tenofovir Alafenamide 50 MG-200 MG-25 MG Oral Tablet [BIKTARVY]

Drug: Bictegravir/Emtricitabine/Tenofovir Alafenamide 50 MG-200 MG-25 MG Oral Tablet [BIKTARVY]
Administer BIC/FTC/TAF 50/200/25 mg tablet by mouth once a day from day 1 to168.
Other Names:
  • Biktarvy
  • BIC/FTC/TAF

    		•
    Nonpolypharmacy

    Nonpolypharmacy: patient is using less than five medications will be considered nonpolypharmacy Nonpolypharmacy Subjects taking Elvitegravir/Cobicistat/Emtricitabine/Tenofovir/Alafenamide 150MG-150MG-200MG-10MG Oral Tablet [Genvoya] or Elevitegravir/Cobicistat/Emtricitabine/Tenofovir disoproxil fumarate 150MG-150MG-200MG-300MG Oral Tablet [Stribild] will switch to Bictegravir/Emtricitabine/Tenofovir Alafenamide 50 MG-200 MG-25 MG Oral Tablet [BIKTARVY]

    Drug: Bictegravir/Emtricitabine/Tenofovir Alafenamide 50 MG-200 MG-25 MG Oral Tablet [BIKTARVY]
    Administer BIC/FTC/TAF 50/200/25 mg tablet by mouth once a day from day 1 to168.
    Other Names:
  • Biktarvy
  • BIC/FTC/TAF

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Probability of PDDI particularly with cobicistat and concurrent medications will be assessed throughout the study. [week 1 to week 24]

      From week 1 to week 24 the study will assess drug's PDDI and concurrent medications which patients are using

    2. Health related quality of life assessments at baseline [week 12 to week 24]

      To evaluate health related quality of life based on HIV Symptom Index (range 0-80, lower scores suggest better quality of life)

    Secondary Outcome Measures

    1. Adherence assessment at baseline [week 4, week 8, week 12 and week 24]

      Study team will keep record of every patients adherence of taking drugs

    2. Lipid panel results at baseline. [week 12 and week 24]

      Lipid panel will be drawn by protocol team and be monitored closely

    3. Blood pressure level at baseline [week 12 and week 24]

      Blood pressure will be drawn by protocol team and be monitored closely

    4. Blood glucose level at baseline [week 12 and week 24]

      Blood glucose will be drawn by protocol team and be monitored closely

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Adult individuals > 18 years of age.

    • Able and willing to provide informed/signed consent.

    • Presence of HIV-1 infection as documented by a licensed ELISA test kit and confirmed by Western blot or HIV RNA.

    • Current antiretroviral therapy, Genvoya or Stribild for HIV-1 infection.

    • At least 1 or more concurrent prescription medication.

    • HIV VL < 50 for over 6 months, no current OI, no cancers

    Exclusion Criteria:

    • Use of drugs of abuse or alcohol which would interfere with adherence or completion of this study.

    • Current antiretroviral therapy other than GenvoyaTM or StribildTM for HIV-1 infection.

    • Pregnancy or breast-feeding. Women of childbearing potential must have a negative serum or urine pregnancy test within 14 days prior to study entry and day of entry.

    • Chronic, severe, or other medical conditions that, in the opinion of the investigator, would interfere with the subject's ability to participate in the protocol.

    • Use of prohibited protocol-specified drugs, prescription or over-the-counter medication (see Section 6.4.2) within 14 days prior to study entry.

    • Moderate or severe cognitive impairment by history that, in the opinion of the investigator, would interfere with the subject's ability to participate in the protocol

    • Laboratory parameters documented within 21 days prior to study entry that would increase the risk for adverse events:

    1. Hemoglobin < 12.5 g/dL for men; < 11.5 g/dL for women;

    2. Platelet count < 100,000 platelets/mm 3;

    3. AST (SGOT) or ALT (SGPT) > 1.5 x the upper limit of normal (ULN);

    4. Estimated GFR < 30 ml/min

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Evergreen Health Buffalo New York United States 14201

    Sponsors and Collaborators

    • State University of New York at Buffalo
    • Gilead Sciences

    Investigators

    • Principal Investigator: Qing Ma, PharmD, PhD, University at Buffalo

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    Responsible Party:
    Qing Ma, PharmD, Principal Investigator, State University of New York at Buffalo
    ClinicalTrials.gov Identifier:
    NCT05064020
    Other Study ID Numbers:
    • STUDY00003629
    First Posted:
    Oct 1, 2021
    Last Update Posted:
    Oct 1, 2021
    Last Verified:
    Sep 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    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
    Keywords provided by Qing Ma, PharmD, Principal Investigator, State University of New York at Buffalo
    HIV
    Switch
    Bictegravir
    Drug-drug interaction
    Polypharmacy
    Elderly
    Adherence
    Quality of life
    Additional relevant MeSH terms:
    Tenofovir
    Emtricitabine
    Emtricitabine tenofovir alafenamide

    Study Results

    No Results Posted as of Oct 1, 2021