Clinical trial NCT01318096: 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
Overall status: UNKNOWN
Phase: NA
Conditions: HBV Coinfection
HIV Infections
Keywords: safety
efficacy
raltegravir
HBV/HIV co-infection
Lead sponsor: Yunnan AIDS Care Center
Sponsor class: OTHER
First posted: 2011-03-18
Enrollment: 60
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: 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.

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

Primary outcomes:
measure: Frequency and severity of adverse events
timeFrame: In 48 weeks (from baseline to study completion at 48 weeks)
Secondary outcomes:
measure: Change of plasma HIV-1 RNA levels
timeFrame: week 0,24 and 48
measure: Change of Peripheral blood CD4 cell counts
timeFrame: week 0,4,8,12,24,36 and 48
measure: Change of plasma HBV-DNA levels
timeFrame: week 0,12,24,36,and 48
measure: Change of serum total bilirubin levels（TBI）
timeFrame: week 0,2,4,8,12,24,36 and 48
measure: Proportion of subjects with HBeAg seroconversion (HBeAg loss and presence of anti HBe)
timeFrame: week 0,12,24,36,and week 48
measure: Emergence of drug resistance mutations, if appropriate
timeFrame: week 0, 24 and 48
measure: Paired liver biopsy comparison according to inflammatory activity and fibrosis score
timeFrame: week 0 and 48
measure: Change of serum alanine aminotransferase levels (ALT)
timeFrame: week 0,2,4,8,12,24,36 and 48
measure: Change of serum aspartate aminotransferase levels (AST)
timeFrame: week 0,2,4,8,12,24,36 and 48
measure: Change of blood urine nitrogen levels (BUN)
timeFrame: week 0,2,4,8,12,24,36 and 48
measure: Change of serum creatinine levels (SCr)
timeFrame: week 0,2,4,8,12,24,36 and 48
measure: Change of blood haemoglobin levels (HB)
timeFrame: week 0,2,4,8,12,24,36 and 48
measure: Change of white blood cell counts (WBC)
timeFrame: week 0,2,4,8,12,24,36 and 48
measure: Change of blood platelet counts (PLT)
timeFrame: week 0,2,4,8,12,24,36 and 48
measure: Change of urine protein levels
timeFrame: week 0,2,4,8,12,24,36 and 48
Other outcomes:
Locations:
city: Kunming
country: China
facility: Yunnan Provincial Hospital of Infectious Diseases/Yunnan AIDS Care Center
state: Yunnan Provice
Study officials:
affiliation: Yunnan Provincial Hospital of Infectious Diseases/Yunnan AIDS Care Center
name: Cheng Xi Wang, M.D.
role: PRINCIPAL_INVESTIGATOR
References: