South African Medical Unit, Médecins Sans Frontières, Johannesburg, South Africa.
PLoS One. 2010 Feb 17;5(2):e9183. doi: 10.1371/journal.pone.0009183.
The majority of antiretroviral treatment programmes in sub-Saharan Africa are scaling up antiretroviral treatment using a fixed dose first-line antiretroviral regimen containing stavudine, lamivudine, and nevirapine. One of the primary concerns with the use of this regimen is nevirapine-associated hepatotoxicity.
METHODOLOGY/PRINCIPAL FINDINGS: Study participants were 1809 HIV-infected, antiretroviral naïve adults initiating nevirapine-based antiretroviral therapy between November 2002 and December 2006. The primary outcome was early hepatotoxicity. Secondary outcomes were associations with hepatotoxicity and mortality at six months. The cumulative proportion of early hepatotoxicity ranged from 1.0-2.0% giving an incidence-rate at 102 days of 3.6-7.6 per 100 person-years. Median time to hepatotoxicity was 32 (IQR 28-58) days. At 12 weeks, only 8% of patients had alanine aminotransferase monitoring at all the time-points recommended by national guidelines. No association was found between age, gender, baseline CD4 count, concurrent tuberculosis infection, prior participation in a prevention of mother-to-child-transmission program, or baseline weight and early hepatotoxicity. There was no association between early hepatotoxicity and mortality.
The cumulative proportion of early hepatotoxicity in nevirapine based antiretroviral therapy was low in this resource-constrained setting. Hepatotoxicity was not associated with mortality. Frequent routine monitoring of alanine aminotransferase proved difficult to implement in this public sector primary care programme. Focused monitoring in the first month may be a more cost-effective and pragmatic option in settings with limited resources. Correlation with clinical signs and symptoms may allow future alanine aminotransferase testing to be dictated by clinical criteria.
在撒哈拉以南非洲，大多数抗逆转录病毒治疗方案都在扩大使用包含司他夫定、拉米夫定和奈韦拉平的固定剂量一线抗逆转录病毒方案的抗逆转录病毒治疗。使用该方案的主要关注点之一是奈韦拉平相关的肝毒性。
方法/主要发现：研究对象为 1809 名 HIV 感染、抗逆转录病毒初治的成年人，他们在 2002 年 11 月至 2006 年 12 月期间开始接受基于奈韦拉平的抗逆转录病毒治疗。主要结局是早期肝毒性。次要结局是与 6 个月时肝毒性和死亡率的相关性。早期肝毒性的累积比例在 1.0-2.0%之间，102 天的发病率为每 100 人年 3.6-7.6 例。肝毒性的中位时间为 32 天（IQR 28-58）。在 12 周时，只有 8%的患者按照国家指南推荐的所有时间点进行了丙氨酸氨基转移酶监测。年龄、性别、基线 CD4 计数、并发结核病感染、以前参加过母婴传播预防项目、基线体重与早期肝毒性均无相关性。早期肝毒性与死亡率之间也无相关性。
在这个资源有限的环境中，基于奈韦拉平的抗逆转录病毒治疗中早期肝毒性的累积比例较低。肝毒性与死亡率无关。在这个公共部门初级保健方案中，频繁进行常规丙氨酸氨基转移酶监测很难实施。在资源有限的情况下，在第一个月进行重点监测可能是一种更具成本效益和更实用的选择。与临床症状和体征相关联可能使未来的丙氨酸氨基转移酶检测可以根据临床标准来决定。
