Efficacy of Efavirenz 400mg vs. 600mg Combined With Lamivudine and Tenofovir in Treatment Naive HIV Infection

Peking Union Medical College Hospital

The present study will be a randomized controlled study in which 500 treatment-naive HIV patients will be randomized 1:1 to Efaviren 400mg v.s. 600mg combined with lamivudine and tenofovir. The whole cohort will be followed for two years. Efficacy and safety of each regimen will be evaluated throughout the study.

Study Overview

• Status: Unknown
• Conditions: HIV/AIDS; Mental Impairment
• Intervention / Treatment: Drug: Efavirenz 400Mg Oral Tablet; Drug: Efavirenz 600Mg Oral Tablet

Detailed Description

As efaviren has been commonly used as the first-line therapy in HIV infection worldwide, its major side effect i.e. the mental effects have been noticed and has a major influence on the adherence and efficacy of ART regimen. Mental effects of efaviren have been especially critical in Chinese patients, as the effective and toxic ranges of efaviren plasma concentration in Chinese patients are very close to each other.

In this study, 500 treatment-naive Chinese patients with a body weight < 60kg will be screened and recruited. Patients will be randomized 1:1 to efaviren 400mg v.s. 600mg combined with lamivudine and tenofovir. All patients will be followed regularly for 2 years, at 0, 2w, 4w, 3m and every 3 months. Virological and immunological measurements will be done at each visit. Meanwhile, various mental scales will be performed at each visit to evaluate the mental effects of each arm.

• Study Type: Interventional
• Enrollment (Anticipated): 500
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Peking Union Medical College Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Provision of signed and dated informed consent form
• Willingness and availability to engage in study activities for the duration of the study
• Age between 18-65
• Documented HIV-1 infection (confirmed by Western blot)
• Received no prior antiretroviral therapy

Exclusion Criteria:

• Pregnancy or breastfeeding or anticipated pregnancy in two years
• History of AIDS-defining illness
• Hemoglobin < 9g/dl；or peripheral white blood cell counts < 2000/μl；or neutrophil counts < 1000 /μl；or platelet count < 75,000/μl；
• Liver disease (transaminase and alkaline phosphatase levels more than three times the upper limit of the normal range (ULN), bilirubin level more than 2.5 times the ULN)
• Chronic kidney disease (serum creatinine level more than 1.5 times the ULN)
• Patients with a history of injection drug usage
• Patients with a history of mental disorders

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Efavirenz 400MG Oral Tablet; Recruited treatment-naive HIV infected patients will be given Lamivudin 300mg per day, tenofovir 300mg per day and efavirenz 400mg per day as antiretroviral treatment.	Drug: Efavirenz 400Mg Oral Tablet; The experimental arm will receive 400mg efavirenz per randomization with other two antiretroviral medication (tenofovir and lamivudine).
Active Comparator: Efavirenz 600MG Oral Tablet; Recruited treatment-naive HIV infected patients will be given Lamivudin 300mg per day, tenofovir 300mg per day and efavirenz 600mg per day, per standard dose.	Drug: Efavirenz 600Mg Oral Tablet; The active comparator arm will receive 600mg efavirenz per randomization with other two antiretroviral medication (tenofovir and lamivudine).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline Virological measurements at 12 weeks	Plasma viral load	12 weeks
Change from Baseline Virological measurements at 24 weeks	Plasma viral load	24 weeks
Change from Baseline Virological measurements at 48 weeks	Plasma viral load	48 weeks
Change from Baseline Virological measurements at 72 weeks	Plasma viral load	72 weeks
Change from Baseline Virological measurements at 96 weeks	Plasma viral load	96 weeks
Change from Baseline Immunological measurements at 12 weeks	CD4 T cell count	12 weeks
Change from Baseline Immunological measurements at 24 weeks	CD4 T cell count	24 weeks
Change from Baseline Immunological measurements at 48 weeks	CD4 T cell count	48 weeks
Change from Baseline Immunological measurements at 72 weeks	CD4 T cell count	72 weeks
Change from Baseline Immunological measurements at 96 weeks	CD4 T cell count	96 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse effects measured by Dizziness Handicap Inventory	Measure statistically significant difference in perception of dizziness by administering the Dizziness Handicap Inventory (DHI) between two groups at different time point. The 25-item tool comprises three sub-scales: physical (DHI-P; 7 items), emotional (DHI-E; 9 items), and functional (DHI-F; 9 items) and each item is scored from 0 to 4. Grading standard: 0-30 points is defiend as minor obstacles, 31-60 points as moderate obstacle, and 61-100 points as serious obstacle with high risk of falling.	0, 12, 24, 48, 72, 96 weeks
Adverse effects measured by Hamilton Depression Scale-24	Measure statistically significant difference in perception of depression by administering the Hamilton Depression Scale-24 (HAMD-24) between two groups at different time point. The Hamilton Depression Rating Scale (HAMD) has a total of 24 items. 14 items were scored from 0 to 4, and 10 items were scored from 0 to 2. The total score that less than 8 points is defined as no depression, 8 to 20 points as may be depression, scores that more than 20 is defined as mild or moderate depression, and more than 35 points as severe depression.	0, 12, 24, 48, 72, 96 weeks
Adverse effects measured by Pittsburgh Sleep Quality Index	Measure statistically significant difference in perception of sleep quality by administering the Pittsburgh Sleep Quality Index (PSQI) between two groups at different time point. PSQI was used to assess the sleep quality of subjects in the last month. It consists of 19 self-evaluation items and 5 other evaluation items, of which only 18 self-evaluation items participate in scoring. 18 items constitute 7 components, and each component is scored according to 0 ~ 3 grades. The PSQI total score ranges from 0 to 21. The higher the score indicates the worser sleep quality.	0, 12, 24, 48, 72, 96 weeks

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Investigators: Principal Investigator: Taisheng Li, PhD, MD, Peking Union Medical College Hospital

Publications and helpful links

General Publications

• Tongtong Y, Shenghua H, Yin W, Lin C, Huanxia L, Chunrong L, Ruifeng Z, Xiaojing Y, Yuan Y, Yuanhong H, Ke Y. Effectiveness and Safety of Dolutegravir Versus Efavirenz-Based Antiviral Regimen in People Living With HIV-1 in Sichuan Province of China: A Real-World Study. J Acquir Immune Defic Syndr. 2022 Oct 1;91(S1):S1-S7. doi: 10.1097/QAI.0000000000003041.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2018
• Primary Completion (Anticipated): December 1, 2020
• Study Completion (Anticipated): August 1, 2021

Study Registration Dates

• First Submitted: July 15, 2018
• First Submitted That Met QC Criteria: July 3, 2020
• First Posted (Actual): July 9, 2020

Study Record Updates

• Last Update Posted (Actual): July 9, 2020
• Last Update Submitted That Met QC Criteria: July 3, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Efavirenz
• Other Study ID Numbers: CACT 1809

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No