INSTI's For The Management of HIV-associated TB

NCT ID: NCT04734652

Last Updated: 2025-10-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 122 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-02-18
• Study Completion Date: 2024-08-31

Brief Summary

This study is being conducted to assess the antiretroviral activity of a fixed-drug, single tablet, combination of Bictegravir 50mg/ Emtricitabine 200mg/ Tenofovir alafenamide 25mg (Biktarvy®) dosed twice daily in HIV-1 infected, ART-naïve patients with TB co-infection receiving a rifampicin-based tuberculosis (TB) treatment regimen. This study will assess the activity of Bictegravir and dolutegravir-containing ART regimens in patients with drug-susceptible TB through 48 weeks

Detailed Description

Primary objective: To characterize viral suppression rates (proportion of patients with suppressed viral load) at week 24 in the BIC arm

Secondary objectives:

To characterize viral suppression rates at weeks 12, 24 and 48 in the standard of care treatment (SOC) arm (currently, TDF 300mg/3TC 300mg/DTG 50mg) and at weeks 12 and 48 in the BIC/FTC/TAF arm.

To compare the pharmacokinetics (PK) of BIC when given twice daily and co-administered with Rifampicin during tuberculosis treatment vs when given alone after discontinuation of Rifampicin

To assess the incidence of TB associated IRIS in each arm, through week 24.

To characterize the tolerability of treatment in each arm by assessing frequency of clinician-initiated treatment interruptions or switches through week 48.

To assess frequency of ART drug resistance mutations in participants with detectable viral load at study visit weeks 24 and 48.

Conditions

HIV/AIDS; Tuberculosis, Pulmonary

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

BIC arm

The Intervention Arm ART regimen is a fixed-drug combination of a single tablet co-formulated regimen containing Bictegravir 50mg Emtricitabine 200mg and tenofovir alafenamide 25mg (BIC/FTC/TAF; Biktarvy®) that will be taken twice a day during rifampicin-containing TB treatment and 2 weeks after stopping TB treatment, thereafter the BIC/FTC/TAF single tablet co-formulation will be taken once daily.

Group Type: EXPERIMENTAL

Biktarvy®

Intervention Type: COMBINATION_PRODUCT

Biktarvy® is a fixed dose combination, single tablet containing bictegravir (BIC), emtricitabine (FTC), and tenofovir alafenamide (TAF) for oral administration.

BIC is an integrase strand transfer inhibitor (INSTI). FTC, a synthetic nucleoside analog of cytidine, is an HIV nucleoside analog reverse transcriptase inhibitor (HIV NRTI). TAF, an HIV NRTI, is converted in vivo to tenofovir, an acyclic nucleoside phosphonate (nucleotide) analog of adenosine 5'-monophosphate. Each tablet contains 50 mg of BIC (equivalent to 52.5 mg of bictegravir sodium), 200 mg of FTC, and 25 mg of TAF (equivalent to 28 mg of tenofovir alafenamide fumarate) and the following inactive ingredients: croscarmellose sodium, magnesium stearate, and microcrystalline cellulose.

DTG Arm

Dolutegravir 50mg /Lamivudine 300mg/ Tenofovir 300mg (TLD- fixed-drug combination single tablet) plus Dolutegravir 50mg evening dose during TB treatment and for two weeks after completion of TB treatment, then TLD once daily thereafter- as per Standard of Care (SOC)

Group Type: ACTIVE_COMPARATOR

TLD- fixed-drug combination single tablet

Intervention Type: COMBINATION_PRODUCT

Standard of care Dolutegravir-based regimen

Interventions

Biktarvy®

Biktarvy® is a fixed dose combination, single tablet containing bictegravir (BIC), emtricitabine (FTC), and tenofovir alafenamide (TAF) for oral administration.

BIC is an integrase strand transfer inhibitor (INSTI). FTC, a synthetic nucleoside analog of cytidine, is an HIV nucleoside analog reverse transcriptase inhibitor (HIV NRTI). TAF, an HIV NRTI, is converted in vivo to tenofovir, an acyclic nucleoside phosphonate (nucleotide) analog of adenosine 5'-monophosphate. Each tablet contains 50 mg of BIC (equivalent to 52.5 mg of bictegravir sodium), 200 mg of FTC, and 25 mg of TAF (equivalent to 28 mg of tenofovir alafenamide fumarate) and the following inactive ingredients: croscarmellose sodium, magnesium stearate, and microcrystalline cellulose.

Intervention Type: COMBINATION_PRODUCT

TLD- fixed-drug combination single tablet

Standard of care Dolutegravir-based regimen

Intervention Type: COMBINATION_PRODUCT

Other Intervention Names

Dolutegravir 50mg /Lamivudine 300mg/ Tenofovir 300mg

Eligibility Criteria

Inclusion Criteria

• Adults ≥ 18 years of age with Karnofsky score ≥ 70
• Confirmed rifampicin-susceptible tuberculosis and/or
• On first-line rifampicin-based tuberculosis treatment (not > 8 weeks at the time of enrolment)
• Documented HIV-1 infection, ART-naïve OR ART non-naïve (patients to have no exposure to ART medication at least ≥ 3 months at the time of enrollment)
• Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73m2
• Alanine aminotransferase (ALT) ≤3 times the upper limit of normal (ULN)
• Total bilirubin ≤2.5 times ULN
• Creatinine ≤2 times ULN
• Hemoglobin ≥ 7.0 g/dL (6.5 g/dL for females)
• Platelet count ≥ 50,000/mm3
• Absolute Neutrophil Count (ANC) ≥650/mm3
• Able and willing to provide written informed consent
• Female patients agree to use both a barrier and a non-barrier form of contraception during the study, starting at least 14 days prior to enrolment

Exclusion Criteria

• Pregnancy or breastfeeding (or planned pregnancy within 12 months of study entry)
• Prior use of antiretroviral drugs for pre-exposure prophylaxis (PrEP) or post-exposure prophylaxis (PEP) < 3 months at the time of enrolment
• Hepatitis B surface antigen positive OR Hepatitis B virus (HBV) infection OR active systemic infections (other than HIV-1 infection) requiring systemic antibiotic or antifungal therapy current or within 30 days prior to baseline that could, in the opinion of the investigator, interfere with study procedures or assessment of study outcomes
• Participants with a CD4+ cell count of < 50 cells/ μl
• Any verified Grade 4 laboratory abnormality, with the exception of, Grade 4 triglycerides. A single repeat test is allowed during the Screening period to verify a result
• Patients on metformin (> 500mg, 12hourly)
• Patients with an uncontrolled psychiatric co-morbidity. Patients who, in the investigator's judgment, pose a significant suicidality risk. Recent history of suicidal behavior and/or suicidal ideation may be considered as evidence of serious suicide risk
• Other condition or circumstance deemed by clinician/investigators to be detrimental to patient safety or study conduct
• Unwilling to be part of the main pharmacokinetic (PK) study and have PK blood draws done (NB there is a semi-intensive PK substudy which is optional)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 105 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Johns Hopkins University

OTHER

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: collaborator

University of Cape Town

OTHER

Sponsor Role: collaborator

Medical Research Council, South Africa

OTHER

Sponsor Role: collaborator

Centre for the AIDS Programme of Research in South Africa

NETWORK

Sponsor Role: lead

Responsible Party

Anushka Naidoo

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Anushka Naidoo, PhD

Role: PRINCIPAL_INVESTIGATOR

Centre for the AIDS Programme of Research in South Africa (CAPRISA)

Kelly Dooley, MD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University Medical Center

Kogieleum Naidoo, PhD

Role: STUDY_DIRECTOR

Centre for the AIDS Programme of Research in South Africa

Locations

CAPRISA Springfield Clinical Research Site

Durban, KwaZulu-Natal, South Africa

Countries

South Africa

References

Naidoo A, Dooley KE, Naidoo K, Padayatchi N, Yende-Zuma N, Perumal R, Dorse G, Boodhram R, Osuala EC. INSTIs for the management of HIV-associated TB (INSIGHT study): a phase 2b study to evaluate the efficacy, safety and pharmacokinetics of a combination of bictegravir, emtricitabine and tenofovir alafenamide fumarate for the treatment of HIV-1 infection in patients with drug-susceptible tuberculosis on a rifampicin-based treatment regimen: a phase 2b open-label randomised controlled trial. BMJ Open. 2022 Nov 10;12(11):e067765. doi: 10.1136/bmjopen-2022-067765.

Reference Type: DERIVED

PMID: 36356989 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

1R01AI152142-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CAPRISA 093

Identifier Type: -

Identifier Source: org_study_id