洛匹那韦/利托那韦单药治疗作为一种节省核苷类似物的策略，用于预防 HIV-1 母婴传播：ANRS 135 PRIMEVA 期 2/3 随机试验。

Lopinavir/ritonavir monotherapy as a nucleoside analogue-sparing strategy to prevent HIV-1 mother-to-child transmission: the ANRS 135 PRIMEVA phase 2/3 randomized trial.

机构信息

Service de maladies infectieuses, AP-HP, Hôpital Pitié Salpêtrière, Paris, France.

出版信息

Clin Infect Dis. 2013 Sep;57(6):891-902. doi: 10.1093/cid/cit390. Epub 2013 Jun 12.

DOI:10.1093/cid/cit390

PMID:23766338

Abstract

BACKGROUND

Prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV) is usually based on zidovudine-containing regimens, despite potential toxicities. This multicenter trial evaluated whether lopinavir/ritonavir (LPV/r) monotherapy in HIV type 1-infected women not requiring antiretrovirals for themselves could control maternal viral load (VL).

METHODS

Overall, 105 pregnant women with baseline VL <30 000 copies/mL and CD4 ≥350 cells/µL were randomized to start open-label LPV/r 400/100 mg twice daily alone (monotherapy group, n = 69) or combined with zidovudine/lamivudine 300/150 mg twice daily (triple therapy group, n = 36) from 26 gestational weeks to delivery. According to a Fleming 2-stage phase 2 design, monotherapy was considered to be efficacious if at least 59 patients achieved VL <200 copies/mL at 8 weeks of treatment (primary endpoint). Secondary endpoints were VL at delivery and tolerance.

RESULTS

Monotherapy was efficacious as defined: 62 women in the monotherapy group achieved VL <200 copies/mL at 34 weeks' gestation (ie, 8 weeks of treatment; 89.9%; 95% confidence interval [CI], 80.2%-95.8%). At delivery, proportions with VL <200 copies/mL were similar in the monotherapy and triple therapy groups (92.8% vs 97.2%; P = .66); however, fewer had VL <50 copies/mL in the monotherapy group (78.3% vs 97.2%; P = .01). Changes for intolerance were less frequent in the monotherapy than in the triple therapy group (1.4% vs 11.1%, respectively; P = .046). Cesarean delivery and preterm delivery rates did not differ. All children were liveborn; 1 case of HIV-1 transmission occurred in the triple therapy group, none in the monotherapy group (95% CI upper limit = 5.2%).

CONCLUSIONS

LPV/r monotherapy achieved satisfactory virologic efficacy in women treated solely for PMTCT, providing proof of concept for future nucleoside-sparing strategies.

摘要

背景

预防母婴传播（PMTCT）的人类免疫缺陷病毒（HIV）通常基于含齐多夫定的方案，尽管存在潜在的毒性。本多中心试验评估了在不需要自身抗逆转录病毒治疗的情况下，HIV-1 感染的孕妇使用洛匹那韦/利托那韦（LPV/r）单药治疗是否可以控制母体病毒载量（VL）。

方法

共有 105 名基线 VL<30000 拷贝/mL 和 CD4≥350 个/µL 的孕妇被随机分配至开始接受开放性 LPV/r 400/100mg 每日两次单药治疗（单药治疗组，n=69）或联合齐多夫定/拉米夫定 300/150mg 每日两次治疗（三联治疗组，n=36），从 26 孕周开始至分娩。根据 Fleming 两阶段 2 期设计，如果至少 59 名患者在治疗 8 周时达到 VL<200 拷贝/mL（主要终点），则认为单药治疗有效。次要终点为分娩时的 VL 和耐受性。

结果

单药治疗组达到了定义的有效性：62 名孕妇在单药治疗组在 34 孕周时达到 VL<200 拷贝/mL（即治疗 8 周；89.9%；95%置信区间 [CI]，80.2%-95.8%）。在分娩时，单药治疗组和三联治疗组的 VL<200 拷贝/mL 的比例相似（92.8% vs 97.2%；P=0.66）；然而，单药治疗组的 VL<50 拷贝/mL 的比例较低（78.3% vs 97.2%；P=0.01）。单药治疗组比三联治疗组不耐受的变化更少见（分别为 1.4%和 11.1%；P=0.046）。剖宫产和早产率无差异。所有儿童均为活产；三联治疗组发生 1 例 HIV-1 传播，单药治疗组未发生（95%CI上限=5.2%）。