Postgraduate Program on Health Sciences: Infectious Diseases and Tropical Medicine, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
School of Medicine, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
Braz J Infect Dis. 2014 Jan-Feb;18(1):1-7. doi: 10.1016/j.bjid.2013.04.001. Epub 2013 Jul 31.
Darunavir has been proven efficacious for antiretroviral-experienced HIV-1-infected patients in randomized trials. However, effectiveness of darunavir-based salvage therapy is understudied in routine care in Brazil.
Retrospective cohort study of HIV-1-infected patients from three public referral centers in Belo Horizonte, who received a darunavir-based therapy between 2008 and 2010, after virologic failure. Primary endpoint was the proportion of patients with viral load<50 copies/mL at week 48. Change in CD4 cell count was also evaluated. Outcome measures were analyzed on an intent-to-treat basis applied to observational studies. Sensitivity analysis was conducted to evaluate the impact of missing data at week 48. Predictors of virologic failure were examined using rare-event, finite sample, bias-corrected logistic regression.
Among 108 patients, the median age was 44.2 years, and 72.2% were male. They had long-standing HIV-1 infection (median 11.6 years) and advanced disease (76.9% had an AIDS-defining event). All patients had previously received protease inhibitors and nucleoside reverse transcriptase inhibitors, 75% nonnucleoside reverse transcriptase inhibitors, and 4.6% enfuvirtide. The median length of protease inhibitor use was 8.9 years, and 90.8% of patients had prior exposure to unboosted protease inhibitor. Genotypic resistance profile showed a median of three primary protease inhibitor mutations and 10.2% had three or more darunavir resistance-associated mutations. Virologic success at week 48 was achieved by 78.7% (95% CI=69.7-86%) of patients and mean CD4 cell count increase from baseline was 131.5 cells/μL (95% CI=103.4-159.6). In multiple logistic regression analysis, higher baseline viral load (RR=1.04 per 10,000 copies/mL increase; 95% CI=1.01-1.09) and higher number of darunavir resistance-associated mutations (RR=1.23 per each; 95% CI=0.95-1.48) were independently associated with virologic failure.
Virologic suppression is a realistic endpoint for most treatment-experienced patients who begin a darunavir-based therapy outside the controlled conditions of a randomized trial, at routine care settings.
在随机试验中，达芦那韦已被证明对有抗逆转录病毒治疗经验的 HIV-1 感染患者有效。然而，在巴西的常规护理中，对达芦那韦为基础的挽救治疗的有效性研究较少。
这是一项回顾性队列研究，研究对象为来自贝洛奥里藏特的三个公共转诊中心的 HIV-1 感染患者，这些患者在 2008 年至 2010 年间，在病毒学失败后接受了达芦那韦为基础的治疗。主要终点是在第 48 周时病毒载量<50 拷贝/ml 的患者比例。还评估了 CD4 细胞计数的变化。观察性研究的意向治疗分析用于分析结局指标。进行敏感性分析以评估第 48 周缺失数据的影响。使用罕见事件、有限样本、偏倚校正逻辑回归来检查病毒学失败的预测因素。
在 108 例患者中，中位年龄为 44.2 岁，72.2%为男性。他们患有长期 HIV-1 感染（中位时间为 11.6 年）和晚期疾病（76.9%有艾滋病定义性事件）。所有患者均曾接受过蛋白酶抑制剂和核苷逆转录酶抑制剂治疗，75%曾接受过非核苷逆转录酶抑制剂治疗，4.6%曾接受过恩夫韦肽治疗。蛋白酶抑制剂的中位使用时间为 8.9 年，90.8%的患者有未增强的蛋白酶抑制剂暴露史。基因型耐药谱显示中位有三种主要蛋白酶抑制剂突变，10.2%有三种或更多达芦那韦耐药相关突变。第 48 周时，78.7%（95%可信区间=69.7-86%）的患者达到病毒学成功，基线时平均 CD4 细胞计数增加 131.5 个细胞/μL（95%可信区间=103.4-159.6）。在多变量逻辑回归分析中，较高的基线病毒载量（RR=每增加 10,000 拷贝/ml 增加 1.04；95%可信区间=1.01-1.09）和较高的达芦那韦耐药相关突变数量（RR=每增加一个增加 1.23；95%可信区间=0.95-1.48）与病毒学失败独立相关。
在常规护理环境下，在随机试验的对照条件之外开始接受达芦那韦为基础的治疗的大多数有治疗经验的患者，病毒学抑制是一个现实的终点。
