Institute of Pharmacology, Clinical Pharmacology and Toxicology, Dr Subotica 1/III, School of Medicine, University of Belgrade, Belgrade, Serbia.
Biomed Pharmacother. 2012 Jun;66(4):308-11. doi: 10.1016/j.biopha.2011.09.016. Epub 2012 May 15.
Hyperlactatemia and lactic acidosis (LA) are among the most dangerous and life-threatening side effect that occurs during therapy with some nucleoside reverse transcriptase inhibitors (NRTIs), mainly didanosine (ddI) and stavudine (d4T), also known as d-drugs. Therefore, we performed a prospective, follow-up study and aimed to examine the incidence rates (IR) and rate ratios (RR) of hyperlactatemia and LA for each NRTI. Three hundred and ninety-six HIV-patients were included in final analysis comprising 783.8 person-years of follow-up. Between 1st January 2000 and 1st January 2008, 19 cases of hyperlactatemia and 15 cases of LA were recorded. Between regimens with the significant impact for developing hyperlactatemia and LA the lowest IR was for didanosine (IR=2.87 per 100 person-years, 95%CI=0.45-9.25 and IR=4.31 per 100 person-years, 95%CI=1.07-13.91, respectively), and the highest for didanosine+stavudine (IR=10.17 per 100 person-years, 95%CI=1.02-19.76 and IR=7.39 per 100 person-years, 95%CI=1.02-13.05, respectively). Compared to didanosine alone the RR of hyperlactatemia was 2.67 (95%CI=1.11-12.52) for stavudine, and 4.06 (95%CI=1.31-15.48) for didanosine+stavudine. The RR of LA was 3.12 (95%CI=1.13-10.65) for stavudine, and 5.13 (95%CI=1.54-13.37) for didanosine+stavudine in comparison with didanosine alone. Other risk factors for AP were CD4 cell count less than 200 cells/mm³ and female sex. Our results suggest that the use of stavudine alone or in combination with didanosine should not be used as first-line therapy, especially in patients with CD4 cell count less than 200 cells/mm³ and females if other treatment options are available.
高乳酸血症和乳酸酸中毒（LA）是某些核苷逆转录酶抑制剂（NRTIs）治疗过程中最危险和最致命的副作用之一，主要是双脱氧肌苷（ddI）和司他夫定（d4T），也称为 d-药物。因此，我们进行了一项前瞻性随访研究，旨在检查每种 NRTI 的高乳酸血症和 LA 的发生率（IR）和比率（RR）。396 名 HIV 患者被纳入最终分析，包括 783.8 人年的随访。在 2000 年 1 月 1 日至 2008 年 1 月 1 日期间，记录了 19 例高乳酸血症和 15 例 LA 病例。在对发展高乳酸血症和 LA 有显著影响的方案中，ddI 的 IR 最低（IR=2.87/100 人年，95%CI=0.45-9.25 和 IR=4.31/100 人年，95%CI=1.07-13.91），ddI+司他夫定的 IR 最高（IR=10.17/100 人年，95%CI=1.02-19.76 和 IR=7.39/100 人年，95%CI=1.02-13.05）。与 ddI 相比，司他夫定的高乳酸血症 RR 为 2.67（95%CI=1.11-12.52），ddI+司他夫定的 RR 为 4.06（95%CI=1.31-15.48）。与 ddI 相比，LA 的 RR 为司他夫定 3.12（95%CI=1.13-10.65），ddI+司他夫定 5.13（95%CI=1.54-13.37）。AP 的其他危险因素是 CD4 细胞计数<200 个/立方毫米和女性。我们的结果表明，单独使用司他夫定或与 ddI 联合使用不应作为一线治疗，特别是在 CD4 细胞计数<200 个/立方毫米和女性患者中，如果有其他治疗选择。
