Soriano Vincent, Barreiro Pablo, Martin-Carbonero Luz, Vispo Eugenia, Garcia-Samaniego Javier, Labarga Pablo, Gonzalez-Lahoz Juan
Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain.
AIDS Rev. 2007 Apr-Jun;9(2):99-113.
Liver disease is currently the second leading cause of death in HIV-infected persons in Western countries. Hepatitis C virus infection accounts for the majority of cases of hepatic illness in this population. Although great progress has been made in the treatment of chronic hepatitis C in HIV-positive patients, many challenges still remain unsolved. The combination of pegylated interferon plus ribavirin is the current treatment of choice in hepatitis C virus/HIV-coinfected patients, regardless of hepatitis C virus genotype. However, the limited efficacy of this therapy in the HIV setting makes necessary the development of new strategies and/or drugs for the treatment of hepatitis C infection. Several anti-hepatitis C virus compounds are currently under investigation, although most are still in the early stages of clinical development. There is a relatively large group of patients who will be unable to be treated with the current hepatitis C virus medication based on interferon, mainly due to contraindications such as serious neuropsychiatric or cardiovascular history. However, for those without contraindications, treatment should be provided with no restrictions at the start (e.g. asking unnecessarily for a liver biopsy), and reassessed at weeks 4 and 12, considering virologic responses. Treatment should only be continued in early virologic responders. The use of standard doses of ribavirin (1000-1200 mg/day) and for at least 12 months seems crucial to maximize the effect of current hepatitis C treatment in the HIV setting, while no further benefit seems to derive from using higher than recommended pegylated interferon dosages. In patients with rapid virologic response (undetectable viremia at week 4) to anti-hepatitis C therapy, shorter periods of therapy (24 weeks) may be advisable in hepatitis C genotypes 2 and 3. Finally, adequate selection of candidates and careful selection of concomitant antiretroviral medications must be encouraged. Patients with low CD4 percentages (< 15%) should be deferred for treatment and HAART prioritized in order to improve CD4 counts. When possible, nucleoside analogs such as zidovudine, stavudine, and abacavir should be replaced by others having no deleterious interactions with ribavirin (e.g. tenofovir, lamivudine, or emtricitabine). Didanosine should never be coadministered with ribavirin due to potential life-threatening complications.
在西方国家,肝病目前是艾滋病毒感染者的第二大死因。丙型肝炎病毒感染是该人群肝病病例的主要原因。尽管在艾滋病毒阳性患者慢性丙型肝炎的治疗方面已取得巨大进展,但许多挑战仍未得到解决。聚乙二醇化干扰素加利巴韦林联合用药是目前丙型肝炎病毒/艾滋病毒合并感染患者的首选治疗方法,无论丙型肝炎病毒基因型如何。然而,这种疗法在艾滋病毒感染情况下疗效有限,因此有必要开发治疗丙型肝炎感染的新策略和/或药物。目前有几种抗丙型肝炎病毒化合物正在研究中,不过大多数仍处于临床开发的早期阶段。有相当一部分患者无法使用目前基于干扰素的丙型肝炎病毒药物进行治疗,主要是由于严重神经精神病史或心血管病史等禁忌证。然而,对于那些没有禁忌证的患者,开始治疗时不应有任何限制(例如不必要地要求进行肝活检),并在第4周和第12周重新评估,同时考虑病毒学反应。只有早期病毒学应答者才应继续治疗。使用标准剂量的利巴韦林(1000 - 1200毫克/天)并至少持续12个月,对于在艾滋病毒感染情况下最大化当前丙型肝炎治疗效果似乎至关重要,而使用高于推荐剂量的聚乙二醇化干扰素似乎并无进一步益处。对于丙型肝炎病毒治疗有快速病毒学应答(第4周病毒血症检测不到)的患者,对于2型和3型丙型肝炎,较短疗程(24周)可能是可取的。最后,必须鼓励对候选者进行充分筛选,并谨慎选择联合使用的抗逆转录病毒药物。CD4百分比低(<15%)的患者应推迟治疗,并优先进行高效抗逆转录病毒治疗以提高CD4计数。尽可能用与利巴韦林无有害相互作用的其他药物(如替诺福韦、拉米夫定或恩曲他滨)替代齐多夫定、司他夫定和阿巴卡韦等核苷类似物。由于可能出现危及生命的并发症,地丹诺辛绝不应与利巴韦林同时使用。