Safety and Efficacy of Raltegravir+TDF+3TC in HBV/HIV Co-infected Patients

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

In this pilot study, the investigators would examine the safety and efficacy of integrase inhibitor-Raltegravir in the control of HIV/HBV co-infection.

Study Overview

• Status: Unknown
• Conditions: HIV Infections; HBV Coinfection
• Intervention / Treatment: Drug: raltegravir and tenofovir and lamivudine; Drug: efavirenz+tenofovir+lamivudine

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.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Yunnan Provice
    • Kunming, Yunnan Provice, China, 650301
      • Yunnan Provincial Hospital of Infectious Diseases/Yunnan AIDS Care Center

Participation Criteria

Eligibility Criteria

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

Description

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

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: A:Raltegravir + tenofovir+lamivudine	Drug: raltegravir and tenofovir and lamivudine; raltegravir 400mg BID and tenofovir 300mg qd and lamivudine 300mg gd for 48 weeks; Other Names: raltegravir: Isentress
Active Comparator: B:Efavirenz+tenofovir+lamivudine	Drug: efavirenz+tenofovir+lamivudine; efavirenz 600mg QN +tenofovir 300mg qd +lamivudine 300mg qd for 48 weeks; Other Names: efavirenz: Sustiva

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	In 48 weeks (from baseline to study completion at 48 weeks)

Secondary Outcome Measures

Outcome Measure	Time Frame
Change of plasma HIV-1 RNA levels	week 0,24 and 48
Change of Peripheral blood CD4 cell counts	week 0,4,8,12,24,36 and 48
Change of plasma HBV-DNA levels	week 0,12,24,36,and 48
Change of serum total bilirubin levels（TBI）	week 0,2,4,8,12,24,36 and 48
Proportion of subjects with HBeAg seroconversion (HBeAg loss and presence of anti HBe)	week 0,12,24,36,and week 48
Emergence of drug resistance mutations, if appropriate	week 0, 24 and 48
Paired liver biopsy comparison according to inflammatory activity and fibrosis score	week 0 and 48
Change of serum alanine aminotransferase levels (ALT)	week 0,2,4,8,12,24,36 and 48
Change of serum aspartate aminotransferase levels (AST)	week 0,2,4,8,12,24,36 and 48
Change of blood urine nitrogen levels (BUN)	week 0,2,4,8,12,24,36 and 48
Change of serum creatinine levels (SCr)	week 0,2,4,8,12,24,36 and 48
Change of blood haemoglobin levels (HB)	week 0,2,4,8,12,24,36 and 48
Change of white blood cell counts (WBC)	week 0,2,4,8,12,24,36 and 48
Change of blood platelet counts (PLT)	week 0,2,4,8,12,24,36 and 48
Change of urine protein levels	week 0,2,4,8,12,24,36 and 48

Collaborators and Investigators

• Sponsor: Yunnan AIDS Care Center
• Investigators: Principal Investigator: Cheng Xi Wang, M.D., Yunnan Provincial Hospital of Infectious Diseases/Yunnan AIDS Care Center

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Anticipated): July 1, 2012
• Study Completion (Anticipated): September 1, 2013

Study Registration Dates

• First Submitted: March 8, 2011
• First Submitted That Met QC Criteria: March 17, 2011
• First Posted (Estimate): March 18, 2011

Study Record Updates

• Last Update Posted (Estimate): March 18, 2011
• Last Update Submitted That Met QC Criteria: March 17, 2011
• Last Verified: March 1, 2011

More Information

Terms related to this study

• Keywords: safety; efficacy; raltegravir; HBV/HIV co-infection
• Additional Relevant MeSH Terms: Infections; Coinfection; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; HIV Integrase Inhibitors; Integrase Inhibitors; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Tenofovir; Raltegravir Potassium; Lamivudine; Efavirenz
• Other Study ID Numbers: MSD-38154