A risk-factor guided approach to reducing lactic acidosis and hyperlactatemia in patients on antiretroviral therapy.
A risk-factor guided approach to reducing lactic acidosis and hyperlactatemia in patients on antiretroviral therapy.
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DOI：
10.1371/journal.pone.0018736
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发表时间：
2011-04-11
期刊：
影响因子：
3.7
通讯作者：
Bangsberg DR
中科院分区：
文献类型：
--
作者：
Matthews LT;Giddy J;Ghebremichael M;Hampton J;Guarino AJ;Ewusi A;Carver E;Axten K;Geary MC;Gandhi RT;Bangsberg DR
司他夫定继续在许多资源有限的环境中用于抗逆转录病毒治疗方案。在高风险患者中使用齐多夫定代替司他夫定以降低乳酸酸中毒和高乳酸血症（LAHL）的可能性尚未进行研究。在2004年至2007年期间开始ART的抗逆转录病毒初治、HIV感染成人被分为接受含司他夫定或齐多夫定治疗的队列。我们采用考克斯比例风险（PH）回归模型评估了司他夫定或齐多夫定的使用、年龄、性别、体重指数（BMI）、基线CD 4细胞计数、肌酐、血红蛋白、丙氨酸氨基转移酶和白蛋白作为至LAHL时间的预测因子。在2062例患者中（2747患者年（PY）），LAHL的合并发生率在开始司他夫定治疗的患者中为3.2/100 PY，在开始含齐多夫定的ART治疗的患者中为0.34/100 PY（RR 9.26，95% CI：1.28-66.93）。在多变量考克斯PH分析中，司他夫定暴露（HR 14.31，95% CI：5.79-35.30），女性（HR 3.41，95% CI：1.89-6.19），BMI较高（HR 3.21，95% CI：2.16-4.77），肌酐升高（1.63，95% CI：1.12-2.36）、基线时较高的白蛋白（HR 1.04，95% CI：1.01-1.07）和较低的CD 4细胞计数（HR 0.96，95% CI：0.92-1.0）与较高的LAHL发生率相关。在开始使用司他夫定的参与者中，转换为齐多夫定与较低的LAHL率相关（HR 0.15，95% CI：0.06-0.35）。仅限于开始使用司他夫定的BMI≥25 kg/m2的女性的亚组分析也显示，在控制其他风险因素时，改用齐多夫定具有保护作用（HR 0.21，95% CI 0.07 -0.64）。司他夫定暴露、女性和较高的BMI是发生LAHL的强独立预测因素。有乳酸酸中毒危险因素的患者在接受齐多夫定而不是含司他夫定的ART时LAHL较少。继续使用司他夫定的国家应避免在女性和BMI较高的患者中使用这种药物。
Stavudine continues to be used in antiretroviral treatment (ART) regimens in many resource-limited settings. The use of zidovudine instead of stavudine in higher-risk patients to reduce the likelihood of lactic acidosis and hyperlactatemia (LAHL) has not been examined. Antiretroviral-naïve, HIV-infected adults initiating ART between 2004 and 2007 were divided into cohorts of those initiated on stavudine- or zidovudine-containing therapy. We evaluated stavudine or zidovudine use, age, sex, body mass index (BMI), baseline CD4 cell count, creatinine, hemoglobin, alanine aminotransferase, and albumin as predictors of time to LAHL with Cox Proportional Hazards (PH) regression models. Among 2062 patients contributing 2747 patient years (PY), the combined incidence of LAHL was 3.2/100 PY in those initiating stavudine- and 0.34/100 PY in those initiating zidovudine-containing ART (RR 9.26, 95% CI: 1.28–66.93). In multivariable Cox PH analysis, stavudine exposure (HR 14.31, 95% CI: 5.79–35.30), female sex (HR 3.41, 95% CI: 1.89–6.19), higher BMI (HR 3.21, 95% CI: 2.16–4.77), higher creatinine (1.63, 95% CI: 1.12–2.36), higher albumin (HR 1.04, 95% CI: 1.01–1.07), and lower CD4 cell count (HR 0.96, 95% CI: 0.92–1.0) at baseline were associated with higher LAHL rates. Among participants who started on stavudine, switching to zidovudine was associated with lower LAHL rates (HR 0.15, 95% CI: 0.06–0.35). Subgroup analysis limited to women with higher BMI≥25 kg/m2 initiated on stavudine also showed that switch to zidovudine was protective when controlling for other risk factors (HR 0.21, 95% CI .07–0.64). Stavudine exposure, female sex, and higher BMI are strong, independent predictors for developing LAHL. Patients with risk factors for lactic acidosis have less LAHL while on zidovudine- rather than stavudine-containing ART. Switching patients from stavudine to zidovudine is protective. Countries continuing to use stavudine should avoid this drug in women and patients with higher BMI.
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影响因子：
11.8
作者：
Bolhaar, M. G.;Karstaedt, A. S.
通讯作者：
Karstaedt, A. S.
DOI：
10.1097/qai.0b013e31817ae5ef
发表时间：
2008-07-01
影响因子：
3.6
作者：
Rosen, Sydney;Long, Lawrence;Sanne, Ian
通讯作者：
Sanne, Ian
影响因子：
3.8
作者：
Lonergan, JT;Barber, RE;Mathews, WC
通讯作者：
Mathews, WC
影响因子：
3.5
作者：
Kumarasamy, N.;Venkatesh, K. K.;Mayer, K. H.
通讯作者：
Mayer, K. H.
影响因子：
11.8
作者：
Bonnet, F;Bonarek, M;Beylot, J
通讯作者：
Beylot, J