BMS제약의 B형간염치료제 바라크루드 (BARACLUDE, entecavir)가 에이즈 바이러스 치료제 내성을 유발할 수 있다고 FDA가 경고하고 나섰다.
FDA는 병합요법(highly active antiretroviral therapy (HAART))을 쓰고 있지 않는 B형 간염과 에이즈 바이러스에 동시 감염된 31세 남성이 B형 간염 치료를 위해 바라크루드를 사용한 후 치료에 내성을 보이는 변형 HIV가 발견되었다고 밝혔다.
FDA는 의료 종사자에게 병합요법을 하지 않는 에이즈 감염 환자에게서 B형 간염 치료를 위해 바라크루드를 사용하는 경우 내성 HIV 바이러스의 출현을 조심하라고 경고했다.
원문
FDA MedWatch: Baraclude Risk of Developing HIV Resistance Cannot be Excluded When Used in an HIV/HBV Co-infected Patient Not Receiving HAART
ROCKVILLE, Md., Feb. 24, 2007--FDA and Bristol-Myers Squibb notified healthcare professionals of revisions to the MICROBIOLOGY/Antiviral Activity and INDICATIONS AND USAGE/Description of Clinical Studies/Special Populations sections of the prescribing information for Baraclude. The revised labeling is the result of a case report in which a human immunodeficiency virus (HIV) variant containing the M184V resistance substitution was documented during Baraclude treatment for chronic hepatitis B virus (HBV) infection in an HIV/HBV co-infected patient who was not simultaneously receiving highly active antiretroviral therapy (HAART).
Current treatment guidelines recommend Baraclude as an option for treatment of HBV in the HIV/HBV co-infected adult patient who does not qualify for HAART. Healthcare professionals are advised that when considering therapy with Baraclude in an HIV/HBV co-infected patient not receiving HAART, the risk of developing HIV resistance cannot be excluded based on current information.
Read a portion of the Manufacturer's Dear Healthcare Provider Letter below. The complete letter and revised labeling are attached.
Re: Important Information Regarding BARACLUDE® (entecavir) in Patients Co-infected with HIV and HBV
Dear Health Care Provider,
Bristol-Myers Squibb is writing to inform you that the company has received a case report in which the selection of a human immunodeficiency virus (HIV) variant containing the M184V resistance substitution was documented during BARACLUDE treatment for chronic hepatitis B virus (HBV) infection in an HIV/HBV co-infected patient who was not simultaneously receiving highly active antiretroviral therapy (HAART). Current treatment guidelines1-2 recommend BARACLUDE as an option for treatment of HBV in the HIV/HBV co-infected adult patient who does not qualify for HAART; however, in light of the newly-reported case history provided below, BMS advises caution if BARACLUDE is used in this setting.
? BARACLUDE has not been evaluated in HIV/HBV co-infected patients not simultaneously receiving effective HIV treatment.
? When considering therapy with BARACLUDE in an HIV/HBV co-infected patient not receiving HAART, the risk of developing HIV resistance cannot be excluded based on current information.
? Caution is advised if BARACLUDE is used in this setting.
Details of the newly-reported case history are provided below:
? A 31-year-old HIV/HBV co-infected male received combination zidovudine, lamivudine, and nevirapine for less than 1 year in 2000. HAART was discontinued and the patient remained clinically stable with respect to his HIV. In early 2006, with a CD4+ of >500 cells/mm3 and an HIV-1 RNA of approximately 35,000 copies/mL, BARACLUDE monotherapy was initiated for the treatment of HBV. Within 2 months, the HBV DNA decreased by approximately 5.5 log10 IU/mL, and the HIV RNA decreased to approximately 2,000 copies/mL, subsequently remaining below baseline levels. HIV resistance testing at the start of BARACLUDE therapy did not show resistance, but the M184V substitution was detected following 6 months of therapy with BARACLUDE.
This patient is one of three HIV/HBV co-infected patients not receiving HAART in whom a 1-log10 reduction in HIV RNA has been noted while receiving BARACLUDE as treatment for chronic HBV infection.
Bristol-Myers Squibb has assessed the activity of BARACLUDE against HIV-1 in vitro: the EC50 for laboratory strains NL4-3, BRU and LAI was >1 ?M in cell culture assays.3
In addition, BMS has evaluated the use of BARACLUDE 1 mg in the HIV/HBV co-infected population that was receiving simultaneous HAART. These data were from a single randomized, double-blind, placebo-controlled evaluation of the activity of BARACLUDE in 68 HIV/HBV co-infected patients who entered the study with stable HIV-1 RNA <400 copies/mL (mean CD4+ count of 511 cells/mm3). Patients continued their lamivudine-containing HAART regimen (lamivudine dose 300 mg/day) and were assigned to add either BARACLUDE 1 mg once daily (51 patients) or placebo (17 patients) for 24 weeks followed by an open-label phase for an additional 24 weeks where all patients received BARACLUDE (entecavir). At Week 24, BARACLUDE-treated patients had a mean reduction in HBV DNA of -3.65 log10 copies/mL compared with an increase of 0.11 log10 copies/mL in the placebo arm. In this setting, no difference in HIV RNA or CD4+ was noted between the BARACLUDE and placebo treatment groups.
Call 1-800-FDA-1088 (1-800-332-1088)
/이준희 헬스조선 인턴기자(연세대 원주의과대학 본과 4년)