Vispo Eugenia, Barreiro Pablo, Maida Ivana, Mena Alvaro, Blanco Francisco, Rodríguez-Novoa Sonia, Morello Judit, Jimenez-Nacher Inmaculada, Gonzalez-Lahoz Juan, Soriano Vincent
Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain.
HIV Clin Trials. 2010 Jul-Aug;11(4):197-204. doi: 10.1310/hct1104-197.
Raltegravir has demonstrated good antiviral activity and safety profile in twice-daily (bid) dosing. However, its long terminal elimination half-life might allow once-daily (qd) administration.
Consecutive HIV-infected individuals at our clinic under protease inhibitor (PI)-based regimens with plasma HIV-RNA <50 copies/mL for > 24 weeks were invited to replace PIs with raltegravir. Patients were randomly assigned to raltegravir 800 mg qd, 400 mg bid, or twice daily for the first 3 months and then once daily.
A total of 222 patients completed 24 weeks of follow-up on raltegravir (149 once-daily arm, 35 twice-daily arm, and 38 twice-daily to once-daily arm). At inclusion, mean CD4+ count was 574±308 cells/µL. Within 24 weeks, 13 (5.9%) patients experienced virological failure: 12 (6.4%) in the once-daily arms, and 1 (2.9%) in the twice-daily arm (P = .18). The rate of virological failure was 16.2% (12/74) in patients with prior nucleoside reverse transcriptase inhibitor (NRTI) resistance but only 0.7% (1/148) in the rest (P < .001).
A switch from PIs to raltegravir in HIV-infected patients with undetectable plasma HIV-RNA effectively sustains viral suppression, as long as prior NRTI resistance had not been selected. No significant differences were seen when comparing raltegravir twice daily or once daily in this context, although once-daily dosing tended to perform less well.
拉替拉韦在每日两次给药时已显示出良好的抗病毒活性和安全性。然而，其较长的终末消除半衰期可能允许每日一次给药。
邀请我们诊所中接受基于蛋白酶抑制剂（PI）方案治疗且血浆HIV-RNA<50拷贝/mL超过24周的连续HIV感染个体，用拉替拉韦替代PI。患者被随机分配接受800mg每日一次的拉替拉韦、400mg每日两次的拉替拉韦，或在最初3个月每日两次给药，然后改为每日一次给药。
共有222例患者完成了24周的拉替拉韦随访（149例在每日一次给药组，35例在每日两次给药组，38例在从每日两次改为每日一次给药组）。纳入时，平均CD4+细胞计数为574±308个/μL。在24周内，13例（5.9%）患者出现病毒学失败：每日一次给药组12例（6.4%），每日两次给药组1例（2.9%）（P = 0.18）。既往有核苷类逆转录酶抑制剂（NRTI）耐药的患者病毒学失败率为16.2%（12/74），而其余患者仅为0.7%（1/148）（P<0.001）。
在血浆HIV-RNA检测不到的HIV感染患者中，从PI转换为拉替拉韦可有效维持病毒抑制，前提是未选择过既往NRTI耐药。在此背景下，比较拉替拉韦每日两次或每日一次给药时未观察到显著差异，尽管每日一次给药的效果往往稍差。
