AASLD: Long-term Tenofovir for HIV/HBV Coinfection

StephenW

                请注意：艾滋病毒，乙肝病毒合并感染的结果
http://www.hivandhepatitis.com/hepatitis-b/hepatitis-b-topics/hbv-treatment/3328-aasld-long-term-tenofovir-for-hivhbv-coinfection
AASLD: Long-term Tenofovir for HIV/HBV Coinfection

•                                                                                 Category: HBV Treatment
•                 Published on Tuesday, 08 November 2011 00:00
•                                         Written by Liz Highleyman
  

                                                                                               

© Russell Kightley

                                       
               
               
                Tenofovir showed long-term antiviral activity against hepatitis B virus (HBV) lasting 5 to 8 years, with minimal evidence of kidney toxicity, and HBsAg levels declined steadily over time, according to 2 posters presented this week at the American Association for the Study of Liver Diseases Liver Meeting (AASLD 2011) in San Francisco.
        Tenofovir (Viread, also in the Truvada and Atripla coformulations) is active against both HIV and HBV, and treatment guidelines recommend that it be included in antiretroviral therapy (ART) regimens for HIV/HBV coinfected patients. U.S. and European guidelines also recommend that HIV/HBV coinfected people consider earlier ART initiation.
        HBV Viral Load Decline        In the first study, Olivier Lada and colleagues conducted a retrospective analysis of the long-term efficacy and renal (kidney) safety of tenofovir-containing therapy among 166 HIV/HBV coinfected patients followed at Bichat Claude Bernard Hospital in Paris between 2003 and 2008. Nearly 90% were men and the median age was about 42 years.
        Within this cohort, 141 (86%) had been treated with tenofovir; 15 had started treatment with tenofovir plus lamivudine (3TC; Epivir) or emtricitabine (Emtriva) -- both of which are also dually active against HIV and HBV -- while 46 added tenofovir to existing lamivudine therapy. The median duration of tenofovir use was 46 months years (range 25 to 72 months).
        The researchers identified 61 coinfected patients who had detectable HBV DNA at baseline (> 2.3 log IU/mL), 57 with undetectable HBV viral load, and 23 with unavailable data.
        Results

•                 Patients treated with tenofovir-containing regimens had a median CD4 T-cell count of 309 cells/mm3 at baseline, rising to 502 cells/mm3 at the last follow-up visit.
•                 66% had HIV RNA < 50 copies at baseline, compared with 100% at the last visit.
•                 HBV DNA levels fell from a median of 5.9 log IU/mL at baseline to < 1.3 log at the last visit.
•                 All tenofovir-treated patients had undetectable HBV viral load at the end of follow-up.
•                 No HBV virological breakthrough was observed during a median of about 5 years on tenofovir.
•                 22% experienced hepatitis B "e" antigen (HBeAg) and 4% had hepatitis B surface antigen (HBsAg) loss.
•                 3 people had elevated ALT at baseline, but none did so at the last visit.
•                 No patients showed clinically relevant changes in kidney function.
•                 The median creatinine level -- an indicator of potential kidney impairment -- was about the same at baseline and at the last visit (79 vs 80 mcmol/L).
•                 Estimated glomerular filtration rate (GFR) by the MDRD method was 103.5, in the normal range for the study population's age.
  

        Based on these findings, the researchers concluded, "[Tenofovir] associated with lamivudine or emtricitabine showed significant and sustained antiviral activity against HBV in HIV-coinfected patients."
        "A good renal safety profile of [tenofovir] was observed after a median follow-up of 5 years of therapy," they continued, but recommended that patients with pre-existing renal insufficiency should nevertheless be carefully monitored.
        HBsAg Changes        In the second study, Roeland Zoutendijk from Erasmus Medical Center in Rotterdam and colleagues looked at HBsAg changes during long-term tenofovir treatment, with the aim of learning more about HBV clearance.
        This multicenter analysis included 104 HIV/HBV coinfected patients treated with ART regimens containing tenofovir. Again, most (about 90%) were men, the age range was similar, and about 60% were white; about two-thirds were HBeAg positive at baseline.
        The investigators measured HBsAg levels at baseline, month 6, and then annually; the median duration of follow-up was 56 months (range 8-97 months). HBsAg clearance is generally considered a cure, though "occult: or hidden HBV may remain.
        Results

•                 At baseline, HBsAg was significantly higher among HBeAg positive patients compared with HBeAg negative people (4.6 vs 2.8 log IU/mL).
•                 12 HBeAg positive patients (18%) achieved HBeAg seroconversion.
•                 5 HBeAg positive people (8%) and 3 HBeAg negative people (also 8%) achieved HBsAg loss.
•                 HBsAg levels declined steadily among HBeAg positive people, but the decrease was smaller among HBeAg negative patients.
•                 In HBeAg positive patients, immune reconstitution -- as indicated by higher CD4 cell counts at months 6 and 12 -- was correlated with HBsAg decline.
•                 HBeAg positive patients with month 6 HBsAg levels <100 IU/mL had about a 70% probability of HBsAg loss, compared with none of the participants with HBsAg >100 IU/mL.
•                 Extrapolating these numbers, the researchers estimated that the estimated median time to HBsAg loss would be about 18 years for HBeAg positive people and 41 years for HBeAg negative patients.
  

        "HBsAg levels declined steadily, particularly in HBeAg positive patients, during [tenofovir treatment] up to 8 years in HIV/HBV coinfected patients," the investigators concluded. "On-treatment correlation between CD4 count and HBsAg decline indicates a possible role of immune reconstitution in HBsAg loss," they suggested.
        Investigator affiliations:
        Abstract 1428: Hepatologie, Hopital Beaujon and INSERM U773 CRB3, Clichy, France; Service des Maladies Infectieuses et Tropicales, AP-HP Hôpital Bichat Claude Bernard, Paris, France; Laboratoire de Virologie, Service de Microbiologie, AP-HP Hôpital Bichat Claude Bernard, Paris, France; Service de pharmacie, AP-HP Hôpital Bichat Claude Bernard, Paris, France.
        Abstract 1378: Gastroenterology and Hepatology, Erasmus MC, Rotterdam, Netherlands; Medical Microbiology and Karl Landsteiner Laboratory, Academic Medical Center, Amsterdam, Netherlands; Internal Medicine-Infectious Diseases, Erasmus MC, Rotterdam, Netherlands; Internal Medicine, Slotervaart Hospital, Amsterdam, Netherlands; Infectious Diseases, Leids University Medical Center, Leiden, Netherlands; Internal Medicine, Rijnstate Hospital, Arnhem, Netherlands; Virology, Erasmus MC, Rotterdam, Netherlands.
        11/8/11
        References
        O Lada, A Gervais, M Branger, et al. Long-Term Efficacy and Safety of Tenofovir for Treatment of HIV/HBV-Coinfected Patients. 62nd Annual Meeting of the American Association for the Study of Liver Disease (AASLD 2011). San Francisco, November 4-8. 2011. Abstract 1428.
        R Zoutendijk, HL Zaaijer, T de Vries-Sluijs, et al. Tenofovir treatment for up to eight years results in pronounced HBsAg decline in HBeAg-positive HIV/HBV co-infected patients. 62nd Annual Meeting of the American Association for the Study of Liver Disease (AASLD 2011). San Francisco, November 4-8. 2011. Abstract 1378.
       

StephenW

肝病学会：长期为HIV / HBV合并感染泰诺福韦

详情
    分类：乙肝治疗
    发布上周二，2011年11月08日00:00
    书面LIZ Highleyman

泰诺福韦显示对B型肝炎病毒（HBV）的长期抗病毒活性持续5至8岁，最小的肾毒性的证据，和HBsAg水平随着时间的推移逐步下降，根据2海报提交本周在美国协会研究肝病肝会议（AASLD 2011）在旧金山。

替诺福韦（Viread，也Truvada和Atripla coformulations）对HIV和HBV，并建议将其包括在HIV / HBV合并感染患者的抗逆转录病毒疗法（ART）方案治疗指南。美国和欧洲的指引还建议，HIV / HBV合并感染的人认为以前的艺术萌生。
HBV病毒载量下降

在第一项研究中，奥利弗拉达和他的同事进行了一项含有替诺福韦之间Bichat克劳德伯纳德医院在巴黎2003年和2008年之间的166 HIV / HBV合并感染患者的治疗的长期疗效和肾（肾）安全回顾性分析。近90％为男性，平均年龄为42岁左右。

已在这个队列中，有141（86％）与替诺福韦治疗; 15已经开始替诺福韦治疗加拉米夫定（3TC; Epivir）或恩曲他滨（Emtriva） - 这两个也对艾滋病毒和乙肝病毒的双重积极 - 而46泰诺福韦添加到现有的拉米夫定治疗。替诺福韦使用的时间中位数为46个月年（25至72个月）。

研究人员发现61合并感染患者检测不到HBV病毒载量，和不可用的数据23检测到HBV DNA的基线（> 2.3日志国际单位/毫升），57。

结果

    患者治疗与替诺福韦含方案平均CD4 T细胞基线计数309 cells/mm3，在最后随访上升至502 cells/mm3。
    66％的HIV RNA <50份，在基线相比，在上次访问的100％。
    HBV DNA水平下降的中位数为5.9日志IU / mL的基线到最后的访问时间<1.3日志。
    所有替诺福韦治疗的患者在随访结束时HBV病毒载量检测不到。
    无HBV病毒学突破观察期间约5年泰诺福韦的中位数。
    22％的有经验的B型肝炎的“e”抗原（HBeAg）和4％的乙肝表面抗原（HBsAg）的损失。
    3人在基线ALT升高，但均未在上次访问。
    没有患者表现为肾功能临床相关变化。
    肌酐水平中位数 - 一个潜在的肾功能损害的指标 - 大约在同一基线和在最后的访问时间（79 VS 80 mcmol / L）。
    估计肾小球滤过率（GFR）MDRD方法为103.5，为研究人口的年龄在正常范围内。

基于这些发现，研究人员得出结论，“[]与拉米夫定或恩曲他滨相关泰诺福韦呈显著和持续对乙肝的抗病毒活性，在艾滋病毒合并感染的患者。”

“[泰诺福韦一个良好的肾的安全性经过5年的治疗，中位随访观察，”他们继续，但建议，与预先存在的肾功能不全的患者仍应进行认真的监测。
乙肝表面抗原的变化

在第二项研究中中，Roeland Zoutendijk在鹿特丹Erasmus医学中心的同事们在长期替诺福韦治疗期间HBsAg的变化，目的是了解HBV的清除。

这个多中心的分析包括104 HIV / HBV合并感染患者含有替诺福韦的方案与艺术治疗。同样，大多数（约90％）为男性，年龄范围相似，约60％是白人，约三分之二为HBeAg基线积极。

测量基线，6个月的调查，HBsAg水平，然后每年的后续时间中位数为56个月（范围8-97个月）。 HBsAg清除是普遍认为治愈，虽然“隐匿或隐藏的乙肝病毒可能会保持。

结果

    在基线，乙肝表面抗原是HBeAg阳性患者明显高于与HBeAg阴性者（4.6 VS 2.8日志国际单位/毫升）。
    12 e抗原阳性的患者（18％）实现HBeAg血清转换。
    5 HBeAg阳性的人（8％）和3的HBeAg阴性者（8％）HBsAg消失。
    HBsAg水平稳步下降，HBeAg阳性的人之间，但跌幅较小的HBeAg阴性患者之间。
    在HBeAg阳性患者，免疫功能重建 - 更高的CD4细胞计数表明，在6个月和12 - 的HBsAg的下降呈正相关。
    6 e抗原阳性的患者，与一个月的HBsAg水平<100 IU / mL的HBsAg的损失约70％的概率，而与HBsAg的参与者都> 100国际单位/毫升。
    推断这些数字中，研究人员估计，估计的平均时间为HBsAg消失将是e抗原HBeAg阴性患者呈阳性的人，41岁，18岁左右。

“HBsAg水平稳步下降，尤其是在HBeAg阳性患者，[泰诺福韦治疗期间长达8年的HIV / HBV合并感染患者，”研究人员得出结论。 “治疗CD4细胞计数和HBsAg下降之间的相关性，表明在HBsAg消失免疫重建可能发挥的作用，他们的建议。”

调查背景：

1428摘要：Hepatologie总医院Beaujon和INSERM U773 CRB3，克利希，法国;服务DES弊病Infectieuses等Tropicales，AP - HP医院的Bichat克劳德伯纳德，巴黎，法国Laboratoire德Virologie，服务DE Microbiologie，AP - HP医院的Bichat克劳德伯纳德法国巴黎;服务DE pharmacie，AP - HP医院的Bichat克劳德伯纳德，巴黎，法国。

1378摘要：胃肠病学和肝病学杂志，伊拉斯谟的MC，鹿特丹，荷兰，荷兰阿姆斯特丹学术医学中心，医学微生物学和Karl Landsteine​​r的实验室，内科传染性疾病，伊拉斯谟MC，鹿特丹，荷兰，阿姆斯特丹Slotervaart医院内科，荷兰;传染病，Leids大学医学中心，荷兰莱顿;内科，Rijnstate医院，阿纳姆，荷兰;病毒学，伊拉斯谟MC，鹿特丹，荷兰。

11年11月8日

参考文献

Ø拉达，一个热尔韦，M Branger，等。远期疗效和替诺福韦治疗HIV / HBV合并感染患者的安全。美国协会第62届年会肝病（AASLD 2011）的研究。旧金山年11月4-8。 2011年。摘要1428。

ř Zoutendijk，红莲Zaaijer德弗里斯，T - Sluijs公司等。泰诺福韦治疗，在HBeAg阳性的HIV / HBV合并感染患者明显乙肝表面抗原下降至八年结果。美国协会第62届年会肝病（AASLD 2011）的研究。旧金山年11月4-8。 2011年。摘要1378。

MiddleAgeMan

Hi. StephenW:

It is good to know that:  3 HBeAg negative people (also 8%) achieved HBsAg loss

However, I remember that there was a 4 year tenofovir efficacy study (102 hbeag - and 103 hbeag +) by Gilead show that there was 0% hbeag - patients achieve loss of hbsag. Please reference the following:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3002569/

Do you have any thoughts on that?

8%  achieved HBsAg loss
0% acheived hbsag loss

thanks.

Dan

StephenW

回复 MiddleAgeMan 的帖子

No, I find it difficult to generalize about HBV - there are too many variables: individual factors, viral factors, and mutations. As I stated, the results related to HIV/HBV co-infected patients. However, I wanted to show the kinetics of HBsAg levels during treatment, generally.