Back to resultsSafety and Efficacy of Raltegravir+TDF+3TC in HBV/HIV Co-infected Patients
Primary Purpose
HBV Coinfection, HIV Infections
Status
Unknown status
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
raltegravir and tenofovir and lamivudine
efavirenz+tenofovir+lamivudine
Sponsored by
About this trial
This is an interventional treatment trial for HBV Coinfection focused on measuring safety, efficacy, raltegravir, HBV/HIV co-infection
Eligibility Criteria
Inclusion Criteria:
- Ability and willingness to provide written informed consent
- HIV-1 infection, documented in patient medical record. Acceptable forms of documentation include positive HIV antibody or detectable HIV RNA
- HIV-1 antiretroviral therapy naïve
- Chronic HBV infection, defined as HBsAg positive >6 months. Both HBeAg positive and negative subjects will be eligible
- Detectable HBV DNA ( > 300 copies/ml)
- Serum alpha-fetoprotein (AFP) of ≤ 50 ng/ml within 4 weeks of study entry, or if elevated > 50 ng/ml, an imaging study demonstrating no evidence of hepatic tumor within 4 weeks of enrollment
Exclusion Criteria:
- Allergy or sensitivity to study drug
- Pregnancy, breastfeeding or unwillingness/inability to adhere to contraceptive methods for the duration of the study (Female study volunteers must not participate in a conception process (e.g., active attempt to become pregnant). If participating in sexual activity that could lead to pregnancy, the female study volunteer must use the following forms of contraception while receiving study-specific medication(s) and for 30 days after stopping the medication. One of the following methods MUST be used appropriately: (1)Condoms* (male or female) with or without a spermicidal agent; (2)Diaphragm or cervical cap with spermicide; (3)IUD; (4)Hormonal-based method.Condoms are recommended because their appropriate use is the only contraception method effective for preventing HIV transmission.
- Prisoners or subjects who are incarcerated
- Receipt of the following drugs with anti-HBV activity within 90 days prior to study entry or anticipated receipt during the course of the study including: ADV, telbivudine, alpha interferon, and other investigational agents with anti-HBV activity
- Active opportunistic infection
- Other causes of chronic liver disease identified (autoimmune hepatitis, haemochromatosis, Wilsons disease, alfa-1-antitrypsin deficiency)
- Concurrent malignancy requiring cytotoxic chemotherapy
- Decompensated or Child's C cirrhosis
- Any other condition which in the opinion of the investigator might interfere with compliance or outcome of the study
Sites / Locations
- Yunnan Provincial Hospital of Infectious Diseases/Yunnan AIDS Care Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
A:Raltegravir + tenofovir+lamivudine
B:Efavirenz+tenofovir+lamivudine
Arm Description
Outcomes
Primary Outcome Measures
Frequency and severity of adverse events
The investigators will collect the adverse events at every follow-up, and record them in CRFs. All AEs during the study will be analyzed according to the type, frequency and severity.
Secondary Outcome Measures
Change of plasma HIV-1 RNA levels
Change of Peripheral blood CD4 cell counts
Change of plasma HBV-DNA levels
Change of serum total bilirubin levels（TBI）
Proportion of subjects with HBeAg seroconversion (HBeAg loss and presence of anti HBe)
Emergence of drug resistance mutations, if appropriate
Paired liver biopsy comparison according to inflammatory activity and fibrosis score
Change of serum alanine aminotransferase levels (ALT)
Change of serum aspartate aminotransferase levels (AST)
Change of blood urine nitrogen levels (BUN)
Change of serum creatinine levels (SCr)
Change of blood haemoglobin levels (HB)
Change of white blood cell counts (WBC)
Change of blood platelet counts (PLT)
Change of urine protein levels
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01318096
Brief Title
Safety and Efficacy of Raltegravir+TDF+3TC in HBV/HIV Co-infected Patients
Official Title
A Randomized, Pilot Estimation Study to Compare the Safety and Efficacy of Raltegravir+TDF+3TC Versus TDF+3TC+EFV in HBV/HIV Co-infected Patients
Study Type
Interventional
2. Study Status
Record Verification Date
March 2011
Overall Recruitment Status
Unknown status
Study Start Date
March 2011 (undefined)
Primary Completion Date
July 2012 (Anticipated)
Study Completion Date
September 2013 (Anticipated)
3. Sponsor/Collaborators
Name of the Sponsor
Yunnan AIDS Care Center
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
In this pilot study, the investigators would examine the safety and efficacy of integrase inhibitor-Raltegravir in the control of HIV/HBV co-infection.
Detailed Description
There are in total more than 72939 HIV infected people reported in Yunnan, the largest number for any province in China. About 800 HIV inpatients are admitted to our hospital every year, amongst them about 10% co-infected with HBV. HIV and HBV co-infection patients must receive two drugs active against both HIV and HBV, for example Tenofovir disoproxil fumarate (TDF)+ lamivudine (3TC) or TDF+FTC. TDF and 3TC are nucleotide analogues that can inhibit both HIV and HBV DNA polymerases (Dore, Cooper et al. 2004). Combination therapy could decrease drug resistance. In China, TDF is a second-line drug of the national free ART program; however FTC is not in the list of free drugs. There is likely higher risk of causing drug resistance in treating HBV or HIV infection with 3TC or TDF monotherapy than combination therapy.
Raltegravir inhibits the catalytic activity of HIV-1 integrase, and does not significantly inhibit human phosphoryl transferases including DNA polymerases α, β, and γ, and may have less adverse effects. In chronic HBV infection, HBV-DNA does integrate into human DNA which results in difficulty eradicating HBV from the patient's body.
In this pilot study, the investigators would examine the safety and efficacy of integrase inhibitor-Raltegravir in the control of HIV/HBV co-infection.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HBV Coinfection, HIV Infections
Keywords
safety, efficacy, raltegravir, HBV/HIV co-infection
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
60 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
A:Raltegravir + tenofovir+lamivudine
Arm Type
Experimental
Arm Title
B:Efavirenz+tenofovir+lamivudine
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
raltegravir and tenofovir and lamivudine
Other Intervention Name(s)
raltegravir: Isentress
Intervention Description
raltegravir 400mg BID and tenofovir 300mg qd and lamivudine 300mg gd for 48 weeks
Intervention Type
Drug
Intervention Name(s)
efavirenz+tenofovir+lamivudine
Other Intervention Name(s)
efavirenz: Sustiva
Intervention Description
efavirenz 600mg QN +tenofovir 300mg qd +lamivudine 300mg qd for 48 weeks
Primary Outcome Measure Information:
Title
Frequency and severity of adverse events
Description
The investigators will collect the adverse events at every follow-up, and record them in CRFs. All AEs during the study will be analyzed according to the type, frequency and severity.
Time Frame
In 48 weeks (from baseline to study completion at 48 weeks)
Secondary Outcome Measure Information:
Title
Change of plasma HIV-1 RNA levels
Time Frame
week 0,24 and 48
Title
Change of Peripheral blood CD4 cell counts
Time Frame
week 0,4,8,12,24,36 and 48
Title
Change of plasma HBV-DNA levels
Time Frame
week 0,12,24,36,and 48
Title
Change of serum total bilirubin levels（TBI）
Time Frame
week 0,2,4,8,12,24,36 and 48
Title
Proportion of subjects with HBeAg seroconversion (HBeAg loss and presence of anti HBe)
Time Frame
week 0,12,24,36,and week 48
Title
Emergence of drug resistance mutations, if appropriate
Time Frame
week 0, 24 and 48
Title
Paired liver biopsy comparison according to inflammatory activity and fibrosis score
Time Frame
week 0 and 48
Title
Change of serum alanine aminotransferase levels (ALT)
Time Frame
week 0,2,4,8,12,24,36 and 48
Title
Change of serum aspartate aminotransferase levels (AST)
Time Frame
week 0,2,4,8,12,24,36 and 48
Title
Change of blood urine nitrogen levels (BUN)
Time Frame
week 0,2,4,8,12,24,36 and 48
Title
Change of serum creatinine levels (SCr)
Time Frame
week 0,2,4,8,12,24,36 and 48
Title
Change of blood haemoglobin levels (HB)
Time Frame
week 0,2,4,8,12,24,36 and 48
Title
Change of white blood cell counts (WBC)
Time Frame
week 0,2,4,8,12,24,36 and 48
Title
Change of blood platelet counts (PLT)
Time Frame
week 0,2,4,8,12,24,36 and 48
Title
Change of urine protein levels
Time Frame
week 0,2,4,8,12,24,36 and 48
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Ability and willingness to provide written informed consent
HIV-1 infection, documented in patient medical record. Acceptable forms of documentation include positive HIV antibody or detectable HIV RNA
HIV-1 antiretroviral therapy naïve
Chronic HBV infection, defined as HBsAg positive >6 months. Both HBeAg positive and negative subjects will be eligible
Detectable HBV DNA ( > 300 copies/ml)
Serum alpha-fetoprotein (AFP) of ≤ 50 ng/ml within 4 weeks of study entry, or if elevated > 50 ng/ml, an imaging study demonstrating no evidence of hepatic tumor within 4 weeks of enrollment
Exclusion Criteria:
Allergy or sensitivity to study drug
Pregnancy, breastfeeding or unwillingness/inability to adhere to contraceptive methods for the duration of the study (Female study volunteers must not participate in a conception process (e.g., active attempt to become pregnant). If participating in sexual activity that could lead to pregnancy, the female study volunteer must use the following forms of contraception while receiving study-specific medication(s) and for 30 days after stopping the medication. One of the following methods MUST be used appropriately: (1)Condoms* (male or female) with or without a spermicidal agent; (2)Diaphragm or cervical cap with spermicide; (3)IUD; (4)Hormonal-based method.Condoms are recommended because their appropriate use is the only contraception method effective for preventing HIV transmission.
Prisoners or subjects who are incarcerated
Receipt of the following drugs with anti-HBV activity within 90 days prior to study entry or anticipated receipt during the course of the study including: ADV, telbivudine, alpha interferon, and other investigational agents with anti-HBV activity
Active opportunistic infection
Other causes of chronic liver disease identified (autoimmune hepatitis, haemochromatosis, Wilsons disease, alfa-1-antitrypsin deficiency)
Concurrent malignancy requiring cytotoxic chemotherapy
Decompensated or Child's C cirrhosis
Any other condition which in the opinion of the investigator might interfere with compliance or outcome of the study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Cheng Xi Wang, M.D.
Organizational Affiliation
Yunnan Provincial Hospital of Infectious Diseases/Yunnan AIDS Care Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Yunnan Provincial Hospital of Infectious Diseases/Yunnan AIDS Care Center
City
Kunming
State/Province
Yunnan Provice
ZIP/Postal Code
650301
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cheng Xi Wang, M.D.
Phone
86 871 8728060
Email
wxch62597@foxmail.com
First Name & Middle Initial & Last Name & Degree
Cheng Xi Wang, M.D.
12. IPD Sharing Statement
Learn more about this trial
Safety and Efficacy of Raltegravir+TDF+3TC in HBV/HIV Co-infected Patients
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