INSTI's For The Management of HIV-associated TB

NCT04734652 | Completed Phase 2 Results DMC

• 2 other identifiers: CAPRISA 0931R01AI152142-01
• Study Type: interventional
• Target: 122
• Locations: 1 country
• Sites: 1

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

Conditions

HIV/AIDS; Tuberculosis, Pulmonary

Keywords

Biktarvy® is a fixed dose combination; TLD- fixed-drug combination single tablet; Dolutegravir 50mg; HIV/AIDS; Tuberculosis, Pulmonary

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Viral Suppression at Week 24

  Viral suppression rate (HIV-1 RNA \<50 copies/mL) at week 24 in the BIC arm (using the FDA snapshot algorithm).

  Week 24

Secondary Outcomes (7)

• Viral Suppression Rates (HIV-1 RNA <50 Copies/mL) at Weeks 12, 24 and 48 in the DTG Arm and at 12 and 48 Weeks in the BIC Arm

  Week 12 and 48

• BIC Drug Concentrations ("Area Under the Plasma Concentration Versus Time Curve (AUC)"

  Week 4, 8, 12, 24,32 and 40

• BIC Drug Concentrations [Peak Plasma Concentration (Cmax)]

  Week 4, 8, 12, 24, 32 and 40

• BIC Drug Concentrations [Trough/Minimum Plasma Concentration Ctrough)

  Week 4, 8 12, 24, 32 and 40

• The Incidence of TB Associated IRIS

  Through week 24

Study Arms (2)

BIC arm

EXPERIMENTAL

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.

Combination Product: Biktarvy®

DTG Arm

ACTIVE COMPARATOR

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)

Combination Product: TLD- fixed-drug combination single tablet

Interventions

Biktarvy® 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.

BIC arm

TLD- fixed-drug combination single tablet COMBINATION_PRODUCT

Standard of care Dolutegravir-based regimen

Also known as: Dolutegravir 50mg /Lamivudine 300mg/ Tenofovir 300mg

DTG Arm

Eligibility Criteria

• Age: 18 Years - 105 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Centre for the AIDS Programme of Research in South Africa: lead
• Johns Hopkins University: collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• University of Cape Town: collaborator
• Medical Research Council, South Africa: collaborator

Study Sites (1)

CAPRISA Springfield Clinical Research Site

Durban, KwaZulu-Natal, 4001, South Africa

Location

Related Publications (2)

• Naidoo A, Naidoo K, Letsoalo MP, Wasmann RE, Dorse G, Perumal R, Moosa MS, Osuala EC, Boodhram R, Chimukangara B, Wiesner L, Israelski D, Denti P, Rooney JF, Dooley KE; INSIGHT Study Team. Fixed-dose combination bictegravir-emtricitabine-tenofovir alafenamide twice-daily for treatment of HIV during rifampicin-based tuberculosis treatment (INSIGHT Study): a phase 2b, open-label, randomised non-comparative trial. Lancet HIV. 2026 Jan;13(1):e9-e20. doi: 10.1016/S2352-3018(25)00200-0. Epub 2025 Dec 1.

  PMID: 41344350 DERIVED

• 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.

  PMID: 36356989 DERIVED

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; Tuberculosis, Pulmonary

Interventions

bictegravir, emtricitabine, tenofovir alafenamide, drug combination; dolutegravir; Lamivudine; Tenofovir

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Zalcitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dideoxynucleosides; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Limitations and Caveats

Non-comparative design

Results Point of Contact

• Title: Dr Anushka Naidoo
• Organization: CAPRISA

anushka.naidoo@caprisa.org

031 655 0668

Study Officials

• Anushka Naidoo, PhD

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

  PRINCIPAL INVESTIGATOR

• Kelly Dooley, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

• Kogieleum Naidoo, PhD

  Centre for the AIDS Programme of Research in South Africa

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 80 participants for the Intervention Arm ART regimen which 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. 40 participants in the Control 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)

Study Record Dates

• First Submitted: January 11, 2021
• First Posted: February 2, 2021
• Study Start: February 18, 2022
• Primary Completion: January 19, 2024
• Study Completion: August 31, 2024
• Last Updated: October 3, 2025
• Results First Posted: August 15, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Not longer than 12 months after first publication of results. In accordance with WHO stipulations, summary results or a link to summary results will be reported within the trial registration record within 12 months of the study completion date.
• Access Criteria: Access to databases and associated software tools generated under the project will be available for educational, research, and non-profit purposes from bona-fide researchers and/or research organisations.

Locations

ZA (1)