Alvarez-Uria Gerardo, Pakam Raghavakalyan, Naik Praveen Kumar, Midde Manoranjan
Department of Infectious Diseases, Rural Development Trust Hospital, Bathalapalli, AP, India.
PLoS One. 2014 Sep 18;9(9):e108063. doi: 10.1371/journal.pone.0108063. eCollection 2014.
The World Health Organization recommends non-nucleoside reverse transcriptase inhibitors (NNRTIs)-based antiretroviral therapy (ART) for children three years and older. In younger children, starting ART with lopinavir boosted with ritonavir (LPVr) results in lower risk of virological failure, but data in children three years and older are scarce, and long-term ART with LPVr is problematic in resource-poor settings.
Retrospective cohort of children three years and older who started triple ART including LPVr or a NNRTI between 2007 and 2013 in a rural setting in India. Children who started LPVr were switched to nevirapine-based ART after virological suppression. We analysed two outcomes, virological suppression (HIV-RNA <400 copies/ml) within one year of ART using logistic regression, and time to virological failure (HIV-RNA >1000 copies/ml) after virological suppression using Cox proportional hazard regression. A sensitivity analysis was performed using inverse probability of treatment weighting (IPTW) based of propensity score methods.
Of 325 children having a viral load during the first year of ART, 74/83 (89.2%) in the LPVr group achieved virological suppression versus 185/242 (76.5%) in the NNRTI group. In a multivariable analysis, the use of LPVr-based ART was associated with higher probability of virological suppression (adjusted odds ratio 3.19, 95% confidence interval [CI] 1.11-9.13). After IPTW, the estimated risk difference was 12.2% (95% CI, 2.9-21.5). In a multivariable analysis including 292 children who had virological suppression and available viral loads after one year of ART, children switched from LPVr to nevirapine did not have significant higher risk of virological failure (adjusted hazard ratio 1.18, 95% CI 0.36-3.81).
In a cohort of HIV infected children three years and older in a resource-limited setting, an LPVr induction- nevirapine maintenance strategy resulted in more initial virological suppression and similar incidence of virological failure after initial virological suppression than NNRTI-based regimens.
世界卫生组织推荐对3岁及以上儿童采用基于非核苷类逆转录酶抑制剂(NNRTIs)的抗逆转录病毒疗法(ART)。对于年龄较小的儿童,开始使用洛匹那韦利托那韦(LPVr)增强型抗逆转录病毒疗法可降低病毒学失败风险,但3岁及以上儿童的数据较少,且在资源匮乏地区长期使用LPVr进行抗逆转录病毒疗法存在问题。
对2007年至2013年期间在印度农村地区开始接受包括LPVr或NNRTI的三联抗逆转录病毒疗法的3岁及以上儿童进行回顾性队列研究。开始使用LPVr的儿童在病毒学抑制后改用基于奈韦拉平的抗逆转录病毒疗法。我们分析了两个结果,使用逻辑回归分析抗逆转录病毒疗法一年内的病毒学抑制(HIV-RNA<400拷贝/ml)情况,以及使用Cox比例风险回归分析病毒学抑制后病毒学失败(HIV-RNA>1000拷贝/ml)的时间。使用基于倾向评分方法的治疗加权逆概率(IPTW)进行敏感性分析。
在抗逆转录病毒疗法第一年有病毒载量的325名儿童中,LPVr组74/83(89.2%)实现了病毒学抑制,而NNRTI组为185/242(76.5%)。在多变量分析中,使用基于LPVr的抗逆转录病毒疗法与病毒学抑制的较高概率相关(调整后的优势比为3.19,95%置信区间[CI]为1.11-9.13)。采用IPTW后,估计风险差异为12.2%(95%CI,2.9-21.5)。在一项包括292名在抗逆转录病毒疗法一年后有病毒学抑制且有可用病毒载量的儿童的多变量分析中,从LPVr改用奈韦拉平的儿童病毒学失败风险没有显著升高(调整后的风险比为1.18,95%CI为0.36-3.81)。
在资源有限环境中一组3岁及以上的HIV感染儿童中,与基于NNRTI的治疗方案相比,LPVr诱导-奈韦拉平维持策略导致更多的初始病毒学抑制,且初始病毒学抑制后病毒学失败的发生率相似。