Clinical trial NCT04513379: Efficacy of 400 mg Efavirenz Versus Standard 600 mg Dose in HIV/TB Co-infected Patients
Official title: Efficacy and Safety of 400 mg Efavirenz Versus Standard 600 mg Dose in HIV/TB Co-infected Patients Receiving Rifampicin Based Anti-TB Therapy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: HIV Infections
Tuberculosis
Lead sponsor: Shanghai Public Health Clinical Center
Sponsor class: OTHER_GOV
First posted: 2020-08-14
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: TB is the most common cause of death in patients with HIV worldwide. Rifampicin \[RIF\] is the cornerstone of anti-TB therapy. Current guideline recommend efavirenz (EFV) 600mg per day as the first of choice for HIV/TB co-infection. Co-administration of EFV with RIF decrease the plasma concentration of EFV. Because of better safety profiles, EFV 400mg has replaced the EFV 600mg as the first-line antiretroviral therapy in people living with HIV. However, the efficacy of EFV 400mg when co-administrated with RIF in HIV/TB co-infection is unclear. This study is designed to evaluate the efficacy and safety of EFV 400mg versus EFV 600mg in HIV/TB co-infected patients receiving RIF based anti-TB therapy.


Eligibility criteria: Inclusion Criteria:

* Subject or the subject's legal representative is willing and able to understand and provide signed and dated written informed consent prior to Screening
* Adult subject (at least 18 years of age)
* Naive to antiretroviral therapy (\<=14 days of prior therapy with any antiretroviral drug following a diagnosis of HIV-1 infection)
* CD4+ cell count is \>= 50 cells/ cubic millimetre (mm\^3) at Screening
* A female subject may be eligible to enter and participate in the study if she: is of non-childbearing potential defined as either postmenopausal (12 months of spontaneous amenorrhea and \>=45 years of age) or physically incapable of becoming pregnant or does not want to pregnancy
* New diagnosis of TB (microbiology or molecular methods or clinical diagnosis) and started rifampicin based regimen for less no longer than 8 weeks at screening

Exclusion Criteria:

* Evidence of RIF resistance of Mycobacterium tuberculosis either by culture or validated nucleic acid amplification test
* Concomitant disorders or conditions for which isoniazid, RIF, pyrazinamide, or ethambutol are contraindicated
* Central nervous system TB
* Women who are pregnant or breastfeeding
* Subjects with moderate to severe hepatic impairment (Class B or C) as determined by Child-Pugh classification unstable liver disease
* Anticipated need for hepatitis C virus (HCV) therapy during the study period
* History or presence of allergy or intolerance to the study drugs or their components or drugs of their class
* Subjects who, in the investigator's judgment, pose a significant suicidality risk.
* Treatment with any of the following agents within 28 days of Screening: radiation therapy, cytotoxic chemotherapeutic agents, any immunomodulators that alter immune response
* Exposure to an experimental drug or experimental vaccine within either 28 days, 5 half-lives of the test agent, or twice the duration of the biological effect of the test agent, whichever is longer, prior to the first dose of investigate drug
* Any evidence of primary viral resistance to Nucleoside reverse transcriptase inhibitor (NRTIs), Non-nucleoside reverse transcriptase inhibitor (NNRTIs) based on the presence of any major resistance-associated mutation in the Screening result or, if known, any historical resistance test result.
* Any acute laboratory abnormality at Screening, which, in the opinion of the investigator, would preclude the subject's participation in the study of an investigational compound.

Primary outcomes:
measure: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/Milliliter at Week 48 Using the US Food and Drug Administration (FDA) Snapshot Algorithm
timeFrame: Week 48
Secondary outcomes:
measure: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/Milliliter at Week24 Using the US Food and Drug Administration (FDA) Snapshot Algorithm
timeFrame: Week 24
measure: Percentage of Participants Without Confirmed Virologic Withdrawal and Without Discontinuation Due to Treatment-related Reasons at Week 24 and Week 48
timeFrame: Week 24 and Week 48
measure: Number of Participants With Tuberculosis (TB) Associated Immune Reconstitution Inflammatory Syndrome (IRIS)
timeFrame: Week 12
Other outcomes:
Locations:
Study officials:
affiliation: Shanghai Public Health Clinical Center
name: Jun Chen, M.D
role: PRINCIPAL_INVESTIGATOR
References: