van Vonderen Marit G A, van Agtmael Michiel A, Hassink Elly A M, Milinkovic Ana, Brinkman Kees, Geerlings Suzanne E, Ristola Matti, van Eeden Arne, Danner Sven A, Reiss Peter
Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands.
PLoS One. 2009 May 21;4(5):e5647. doi: 10.1371/journal.pone.0005647.
Lipoatrophy is known to be associated with stavudine as part of the treatment for HIV infection, but it is less clear if this serious side effect is also related to other nucleoside reverse transcriptase inhibitors like zidovudine. We aimed to determine whether zidovudine-sparing first-line antiretroviral therapy would lead to less lipoatrophy and other metabolic changes than zidovudine-containing therapy.
METHODOLOGY/PRINCIPAL FINDINGS: Fifty antiretroviral therapy-naïve HIV-1 infected men with an indication to start antiretroviral therapy were included in a randomized single blinded clinical trial. Randomisation was between zidovudine-containing therapy (zidovudine/lamivudine+lopinavir/ritonavir) and zidovudine-sparing therapy (nevirapine+lopinavir/ritonavir). Main outcome measures were body composition assessed by computed tomography and dual-energy X-ray absorptiometry scan and lipid profile before and after 3, 12, 24 months of antiretroviral therapy. In the zidovudine/lamivudine+lopinavir/ritonavir group, from 3 months onward limb fat decreased progressively by 684+/-293 grams (estimated mean+/-standard error of the mean)(p = 0.02) up to 24 months whereas abdominal fat increased, but exclusively in the visceral compartment (+21.9+/-8.1 cm(2), p = 0.008)). In contrast, in the nevirapine+lopinavir/ritonavir group, a generalized increase in fat mass was observed. After 24 months no significant differences in high density lipoprotein and total/high density lipoprotein cholesterol ratio were found between both treatment groups, but total and low density lipoprotein cholesterol levels were higher in the nevirapine+lopinavir/ritonavir group (6.1+/-0.2 versus 5.3+/-0.2 and 3.6+/-0.1 versus 2.8+/-0.1 mmol/l respectively, p<0.05). Virologic response and safety were comparable in both groups.
CONCLUSIONS/SIGNIFICANCE: Zidovudine/lamivudine+lopinavir/ritonavir, but not nevirapine+lopinavir/ritonavir in antiretroviral therapy-naïve patients, is associated with lipoatrophy and greater relative intraabdominal lipohypertrophy, suggesting that zidovudine/lamivudine contributes to both these features of lipodystrophy. These findings support to no longer consider zidovudine/lamivudine as one of the preferred possible components of first-line antiretroviral therapy where alternative treatments are available.
ClinicalTrials.gov NCT 00122226.
已知脂肪萎缩与司他夫定有关，是治疗HIV感染的一部分，但这种严重副作用是否也与其他核苷类逆转录酶抑制剂如齐多夫定有关尚不清楚。我们旨在确定与含齐多夫定的疗法相比，不含齐多夫定的一线抗逆转录病毒疗法是否会导致更少的脂肪萎缩和其他代谢变化。
方法/主要发现：五十名初治的HIV-1感染男性，有开始抗逆转录病毒治疗的指征，被纳入一项随机单盲临床试验。随机分组为含齐多夫定的疗法（齐多夫定/拉米夫定+洛匹那韦/利托那韦）和不含齐多夫定的疗法（奈韦拉平+洛匹那韦/利托那韦）。主要结局指标是在抗逆转录病毒治疗3个月、12个月、24个月前后，通过计算机断层扫描和双能X线吸收法扫描评估身体成分以及血脂情况。在齐多夫定/拉米夫定+洛匹那韦/利托那韦组，从3个月起肢体脂肪逐渐减少，到24个月时减少了684±293克（估计均值±均值标准误）（p = 0.02），而腹部脂肪增加，但仅在内脏部分（增加21.9±8.1平方厘米，p = 0.008）。相比之下，在奈韦拉平+洛匹那韦/利托那韦组，观察到脂肪量普遍增加。24个月后，两个治疗组之间高密度脂蛋白以及总胆固醇/高密度脂蛋白胆固醇比值无显著差异，但奈韦拉平+洛匹那韦/利托那韦组的总胆固醇和低密度脂蛋白胆固醇水平更高（分别为6.1±0.2与5.3±0.2以及3.6±0.1与2.8±0.1毫摩尔/升，p<0.05）。两组的病毒学反应和安全性相当。
结论/意义：在初治患者的抗逆转录病毒治疗中，齐多夫定/拉米夫定+洛匹那韦/利托那韦与脂肪萎缩和相对更严重的腹内脂肪增多有关，而奈韦拉平+洛匹那韦/利托那韦则不然，这表明齐多夫定/拉米夫定导致了脂肪代谢障碍的这两个特征。这些发现支持在有替代治疗方案时，不再将齐多夫定/拉米夫定视为一线抗逆转录病毒治疗的首选可能组成部分之一。
ClinicalTrials.gov NCT 00122226。
