Ofotokun Ighovwerha, Sheth Anandi N, Sanford Sara E, Easley Kirk A, Shenvi Neeta, White Kelly, Eaton Molly E, Del Rio Carlos, Lennox Jeffrey L
Emory University School of Medicine, Department of Medicine, Division of Infectious Diseases, Atlanta, Georgia 30303, USA.
AIDS Res Hum Retroviruses. 2012 Oct;28(10):1196-206. doi: 10.1089/AID.2011.0336. Epub 2012 Apr 20.
A nucleoside reverse transcriptase inhibitor (NRTI) backbone is a recommended component of standard highly active antiretroviral therapy (sHAART). However, long-term NRTI exposure can be limited by toxicities. NRTI class-sparing alternatives are warranted in select patient populations. This is a 48-week single-center, open-label pilot study in which 60 HIV-infected adults with plasma HIV-1 RNA (<50 copies/ml) on sHAART were randomized (2:1) to lopinavir/ritonavir (LPV/r) 400/100 mg BID+raltegravir (RAL) 400 mg BID switch (LPV-r/RAL arm) or to continue on sHAART. The primary endpoint was the proportion of subjects with HIV-RNA<50 copies/ml at week 48. Secondary efficacy and immunologic and safety endpoints were evaluated. Demographics and baseline lipid profile were similar across arms. Mean entry CD4 T cell count was 493 cells/mm(3). At week 48, 92% [95% confidence interval (CI): 83-100%] of the LPV-r/RAL arm and 88% (95% CI: 75-100%) of the sHAART arm had HIV-RNA<50 copies/ml (p=0.70). Lipid profile (mean ± SEM, mg/dl, LPV-r/RAL vs. sHAART) at week 24 was total-cholesterol 194 ± 5 vs. 176 ± 9 (p=0.07), triglycerides 234 ± 30 vs. 133 ± 27 (p=0.003), and LDL-cholesterol 121 ± 6 vs. 110 ± 8 (p=0.27). There were no serious adverse events (AEs) in either arm. Regimen change occurred in three LPV-r/RAL subjects (n=1, due to LPV-r/RAL-related AEs) vs. 0 in sHAART. There were no differences between arms in bone mineral density, total body fat composition, creatinine clearance, or CD4 T cell counts at week 48. In virologically suppressed patients on HAART, switching therapy to the NRTI-sparing LPV-r/RAL combination produced similar sustained virologic suppression and immunologic profile as sHAART. AEs were comparable between arms, but the LPV-r/RAL arm experienced higher triglyceridemia.
核苷类逆转录酶抑制剂（NRTI）骨干方案是标准高效抗逆转录病毒疗法（sHAART）的推荐组成部分。然而，长期使用NRTI可能会受到毒性的限制。在特定患者群体中，有必要采用不使用NRTI类药物的替代方案。这是一项为期48周的单中心、开放标签的试点研究，60名接受sHAART治疗且血浆HIV-1 RNA水平<50拷贝/毫升的HIV感染成人被随机分组（2:1），分别接受洛匹那韦/利托那韦（LPV/r）400/100毫克每日两次加拉替拉韦（RAL）400毫克每日两次的转换治疗（LPV-r/RAL组）或继续接受sHAART治疗。主要终点是第48周时HIV-RNA<50拷贝/毫升的受试者比例。对次要疗效、免疫学和安全性终点进行了评估。各治疗组的人口统计学特征和基线血脂情况相似。平均入组时CD4 T细胞计数为493个/立方毫米。在第48周时，LPV-r/RAL组92%[95%置信区间（CI）：83 - 100%]的受试者和sHAART组88%（95% CI：75 - 100%）的受试者HIV-RNA<50拷贝/毫升（p = 0.70）。第24周时的血脂情况（均值±标准误，毫克/分升，LPV-r/RAL组与sHAART组）为：总胆固醇194±5对176±9（p = 0.07），甘油三酯234±30对133±27（p = 0.003），低密度脂蛋白胆固醇121±6对110±8（p = 0.27）。两组均未出现严重不良事件（AE）。LPV-r/RAL组有3名受试者（n = 1，因与LPV-r/RAL相关的AE）发生治疗方案变更，而sHAART组为0例。在第48周时，两组在骨密度、全身脂肪成分、肌酐清除率或CD4 T细胞计数方面没有差异。在接受HAART且病毒学得到抑制的患者中，将治疗方案转换为不使用NRTI的LPV-r/RAL联合方案与sHAART产生了相似的持续病毒学抑制效果和免疫学特征。两组的AE相当，但LPV-r/RAL组甘油三酯血症发生率更高。
