Bictegravir in the Elderly Living With HIV (BICEP)

May 31, 2024 updated by: Qing Ma, PharmD, State University of New York at Buffalo

Bictegravir in the Elderly Living With HIV: Impact of Polypharmacy and Multimorbidity (BICEP)

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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 Type

Observational

Enrollment (Estimated)

162

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • Buffalo, New York, United States, 14201
        • Evergreen Health

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

Adult individuals > 18 years of age with HIV-1, currently on antiretroviral therapy, Genvoya or Stribild, at least 1 or more concurrent prescription medication and HIV viral load < 50 c/ml for over 6 months, no current OI, no cancers

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
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:
  • BIC/FTC/TAF
  • Biktarvy
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:
  • BIC/FTC/TAF
  • Biktarvy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Potential Drug Drug Interaction (PDDI)
Time Frame: week 1 to week 24
From week 1 to week 24 the study will assess PDDI and concurrent medications
week 1 to week 24

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adherence
Time Frame: Baseline, week 4, week 8, week 12 and week 24
Study team will evaluate patient adherence
Baseline, week 4, week 8, week 12 and week 24
Lipid panel changes
Time Frame: Baseline and week 24
Lipid panel including total cholesterol, low density lipoprotein, high density lipoprotein, and triglyceride, will be monitored at baseline and week 24
Baseline and week 24
Blood pressure changes
Time Frame: Baseline and week 24
Blood pressure will be monitored at baseline and week 24
Baseline and week 24
Blood glucose changes
Time Frame: Baseline and week 24
Blood glucose will be monitored at baseline and week 24
Baseline and week 24
Health related quality of life
Time Frame: Baseline, week 12 and week 24
Health related quality of life will be evaluated based on HIV Symptom Index (range 0-80, lower scores suggest better quality of life)
Baseline, week 12 and week 24
Neurocognitive impairment
Time Frame: Baseline, week 12 and week 24
Neurocognitive impairment will be evaluated using Montreal Cognitive Assessment (MoCA) at baseline, week 12 and week 24.
Baseline, week 12 and week 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

State University of New York at Buffalo

Collaborators

Gilead Sciences

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 1, 2020

Primary Completion (Estimated)

December 31, 2024

Study Completion (Estimated)

December 31, 2024

Study Registration Dates

First Submitted

July 15, 2020

First Submitted That Met QC Criteria

September 21, 2021

First Posted (Actual)

October 1, 2021

Study Record Updates

Last Update Posted (Estimated)

June 4, 2024

Last Update Submitted That Met QC Criteria

May 31, 2024

Last Verified

May 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STUDY00003629

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

We will share de-identified IPD only.

IPD Sharing Time Frame

The data will be summarized and presented in the conferences and scientific journals.

IPD Sharing Access Criteria

Please contact the principal investigator for an access to IPD.

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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