INSTI's For The Management of HIV-associated TB

Centre for the AIDS Programme of Research in South Africa122 enrolled

Overview

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

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

122

Conditions

HIV/AIDS Tuberculosis, Pulmonary

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.

TLD- fixed-drug combination single tabletCOMBINATION_PRODUCT

Standard of care Dolutegravir-based regimen

Eligibility

Sex: ALLMin age: 18 YearsMax age: 105 Years

Medical Language ↔ Plain English

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)

Locations (1)

CAPRISA Springfield Clinical Research Site

Durban, KwaZulu-Natal, South Africa

Outcomes

Primary Outcomes

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).

Time frame: Week 24

Secondary Outcomes

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

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.

Time frame: Week 12 and 48

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

To assess BIC drug levels (AUC) when given twice daily and co-administered with Rifampicin vs. during TB treatment vs when given alone after TB treatment completion

Time frame: Week 4, 8, 12, 24,32 and 40

BIC Drug Concentrations [Peak Plasma Concentration (Cmax)]

To assess BIC drug levels (Cmax) when given twice daily and co-administered with Rifampicin vs. during TB treatment vs when given alone after TB treatment completion

Time frame: Week 4, 8, 12, 24, 32 and 40

BIC Drug Concentrations [Trough/Minimum Plasma Concentration Ctrough)

To assess BIC drug levels ( Ctrough) when given twice daily and co-administered with Rifampicin vs. during TB treatment vs when given alone after TB treatment completion

Time frame: Week 4, 8 12, 24, 32 and 40

The Incidence of TB Associated IRIS

To assess the incidence of TB associated IRIS in each arm

Time frame: Through week 24

Data from ClinicalTrials.gov

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