Imhof Alexander, Ledergerber Bruno, Günthard Huldrych F, Haupts Stefan, Weber Rainer
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zürich, Switzerland.
Clin Infect Dis. 2005 Sep 1;41(5):721-8. doi: 10.1086/432471. Epub 2005 Jul 29.
Lactic acidosis is a rare but life-threatening complication of combination antiretroviral therapy (CART). Asymptomatic or mildly symptomatic episodes of hyperlactatemia are more frequent, but their clinical relevance is unknown.
The incidences of, risk factors for, and courses of hyperlactatemia and lactic acidosis were prospectively assessed in the following 3 groups at the Zurich center of the Swiss HIV Cohort Study: persons already receiving CART at baseline, treatment-naive persons who initiated CART during the observation period, and persons who received no CART before or during the observation period.
During 4788 person-years of follow-up, a total of 22,678 lactate assessments were performed for 1566 persons; 662 (42.3%) had at least 1 lactate level measurement of > 2.4 mmol/L, and 49 (3.1%) had severe hyperlactatemia (lactate level of > 5.0 mmol/L). The incidence of hyperlactatemia was 227 cases (95% confidence interval [CI], 210-245) and 59 cases (95% CI, 38-93) per 1000 person-years of follow-up among persons with and persons without CART, respectively. During the observation period, the incidence decreased from 459 cases (95% CI, 415-508) to 85 cases (95% CI, 76-107) per 1000 person-years of follow-up, respectively, because of changing CART prescription patterns. Severe hyperlactatemia occurred in treated persons only. In multivariable Cox proportional hazards models, significant risk factors for severe hyperlactatemia were regimens containing stavudine and didanosine (hazard ratio [HR], 6.65; 95% CI, 2.70-16.3) and regimens containing efavirenz (HR, 2.85; 95% CI, 1.31-6.21). Lactic acidosis was diagnosed in 4 of 1566 persons, all of whom were receiving stavudine and didanosine.
Hyperlactatemia was frequently observed in all 3 groups, but severe hyperlactatemia and lactic acidosis were rarely observed among persons who received CART. Lactate monitoring appears to be indicated primarily for persons receiving stavudine and didanosine and for persons who are symptomatic. Long-term follow-up is needed to investigate the risk of novel treatment regimens for hyperlactatemia.
乳酸性酸中毒是联合抗逆转录病毒疗法（CART）罕见但危及生命的并发症。无症状或症状轻微的高乳酸血症发作更为常见，但其临床相关性尚不清楚。
在瑞士艾滋病队列研究苏黎世中心的以下3组人群中，前瞻性评估高乳酸血症和乳酸性酸中毒的发生率、危险因素及病程：基线时已接受CART治疗的人群、观察期内开始接受CART治疗的初治人群，以及观察期之前或期间未接受CART治疗的人群。
在4788人年的随访期间，共对1566人进行了22678次乳酸评估；662人（42.3%）至少有1次乳酸水平测量值>2.4 mmol/L，49人（3.1%）有严重高乳酸血症（乳酸水平>5.0 mmol/L）。接受CART治疗的人群和未接受CART治疗的人群中，高乳酸血症的发生率分别为每1000人年随访227例（95%置信区间[CI]，210 - 245）和59例（95%CI，38 - 93）。在观察期内，由于CART处方模式的改变，每1000人年随访的发生率分别从459例（95%CI，415 - 508）降至85例（95%CI，76 - 107）。严重高乳酸血症仅发生在接受治疗的人群中。在多变量Cox比例风险模型中，严重高乳酸血症的显著危险因素是含司他夫定和去羟肌苷的治疗方案（风险比[HR]，6.65；95%CI，2.70 - 16.3）和含依非韦伦的治疗方案（HR，2.85；95%CI，1.31 - 6.21）。1566人中4人被诊断为乳酸性酸中毒，他们均接受司他夫定和去羟肌苷治疗。
在所有3组人群中均经常观察到高乳酸血症，但接受CART治疗的人群中很少观察到严重高乳酸血症和乳酸性酸中毒。乳酸监测似乎主要适用于接受司他夫定和去羟肌苷治疗的人群以及有症状的人群。需要长期随访以研究新治疗方案导致高乳酸血症的风险。
