Division of Infectious Disease, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America.
PLoS One. 2011 Apr 11;6(4):e18736. doi: 10.1371/journal.pone.0018736.
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.
在许多资源有限的环境中，司他夫定仍然被用于抗逆转录病毒治疗（ART）方案中。为了降低乳酸酸中毒和高乳酸血症（LAHL）的可能性，在高危患者中使用齐多夫定代替司他夫定来替代司他夫定，但尚未对此进行研究。
2004 年至 2007 年间接受抗逆转录病毒治疗的 HIV 感染的初治成人患者分为接受司他夫定或齐多夫定治疗的队列。我们使用 Cox 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 CD4 细胞计数、肌酐、血红蛋白、丙氨酸氨基转移酶和白蛋白作为 LAHL 时间的预测因素。
在 2062 名患者中，共有 2747 人年（PY）发生 LAHL，其中接受司他夫定治疗的患者 LAHL 发生率为 3.2/100 PY，接受齐多夫定治疗的患者 LAHL 发生率为 0.34/100 PY（RR 9.26，95%CI：1.28-66.93）。在多变量 Cox 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）、较高的 BMI（HR 3.21，95%CI：2.16-4.77）、较高的肌酐（HR 1.63，95%CI：1.12-2.36）、较高的白蛋白（HR 1.04，95%CI：1.01-1.07）和较低的 CD4 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 发生率相关（HR 0.15，95%CI：0.06-0.35）。在 BMI≥25kg/m2 的女性初治患者中进行的亚组分析也表明，在控制其他危险因素后，转换为齐多夫定具有保护作用（HR 0.21，95%CI.07-0.64）。
司他夫定暴露、女性和较高的 BMI 是发生 LAHL 的强烈独立预测因素。乳酸酸中毒风险因素患者在使用齐多夫定而不是司他夫定治疗时，LAHL 发生率较低。将患者从司他夫定转换为齐多夫定具有保护作用。继续使用司他夫定的国家应避免在女性和 BMI 较高的患者中使用该药。
