HIV Unit and "Lluita contra la SIDA" Foundation, Hospital Universitari Germans Trias i Pujol, Badalona, Universitat Autònoma de Barcelona, Spain.
Hospital Reina Sofía/IMIBIC, Córdoba, Spain.
Antiviral Res. 2015 Aug;120:79-84. doi: 10.1016/j.antiviral.2015.05.001. Epub 2015 May 12.
Maraviroc is approved for treatment-experienced HIV+ adults in twice-daily administration. Limited data are available on safety, efficacy and use in routine clinical practice, outside of restrictive clinical trials. This retrospective multicenter (27 centers) study included 667 subjects starting a regimen with maraviroc. The primary endpoint was plasma HIV-RNA <50copies/mL and CD4(+) cell count change at 48 and 96weeks (FDA snapshot analysis). 94.4% had CCR5 tropism (58.3% Trofile™, 29.2% population genotype, and 12% genotyping proviral DNA). Half of the subjects received the drug in scenarios or dosages outside the initial approval. Maraviroc was prescribed for salvage in 346 (51.9%) individuals, as a switch strategy due to toxicity in 135 (38.7%), for immune discordance in 75 (11.2%), and for simplification in 48 (7.2%). After salvage therapy, 223 (64.5%) subjects had HIV-RNA <50copies/mL at 48weeks, and 178 (51.4%) at 96weeks. Darunavir/r was included in 224 (64.7%) subjects and associated with higher rates of virological and immunologic efficacy (p<0.001). In multivariate analysis MSM (OR 2.25; 95%CI 1.29-3.94) and baseline HIV-RNA <100,000copies/mL (OR 1.96; 1.06-3.70) were associated with virological suppression. An increase in CD4(+) counts was seen at 48 and 96weeks in subjects with immune discordance (p<0.001). Maraviroc was used once-daily in 142 (21.3%) subjects overall, and 68 (57.4%) in switch/simplification. No new safety signals were identified. Besides in salvage regimens, maraviroc was frequently used in switch due to toxicity, simplification, and immune discordance. The efficacy in salvage in clinical practice was higher than in phase III clinical trials, likely due to availability of new active drugs in the regimen. These results increase our understanding of the efficacy, safety, and conditions of prescription of maraviroc beyond the initial registrational trials and the early manufacturer pharmacovigilance programs.
马拉维若在每日两次给药方案中获批用于治疗有经验的 HIV 感染者。在限制性临床试验之外，在常规临床实践中，关于安全性、疗效和使用情况的数据有限。这项回顾性多中心（27 个中心）研究纳入了 667 名开始使用马拉维若治疗的患者。主要终点是 48 周和 96 周时血浆 HIV-RNA<50 拷贝/mL 和 CD4(+)细胞计数的变化（FDA 快照分析）。94.4%的患者存在 CCR5 嗜性（58.3% Trofile™、29.2%人群基因型和 12%基因型前病毒 DNA）。一半的患者在初始批准之外的方案或剂量下接受了药物治疗。346 名（51.9%）患者将马拉维若用于挽救治疗，135 名（38.7%）患者因毒性而改用该药，75 名（11.2%）患者因免疫不和谐，48 名（7.2%）患者因简化方案而使用该药。挽救治疗后，223 名（64.5%）患者在 48 周时 HIV-RNA<50 拷贝/mL，178 名（51.4%）患者在 96 周时 HIV-RNA<50 拷贝/mL。224 名（64.7%）患者中包含了达芦那韦/利托那韦，与更高的病毒学和免疫疗效相关（p<0.001）。多变量分析显示，MSM（OR 2.25；95%CI 1.29-3.94）和基线 HIV-RNA<100,000 拷贝/mL（OR 1.96；1.06-3.70）与病毒学抑制相关。在免疫不和谐的患者中，在第 48 周和第 96 周观察到 CD4(+)计数增加（p<0.001）。马拉维若在总体 142 名（21.3%）患者中每日使用一次，在转换/简化方案中 68 名（57.4%）患者中每日使用一次。未发现新的安全性信号。除了挽救治疗方案外，由于毒性、简化方案和免疫不和谐，马拉维若也常被用于转换治疗。临床实践中的挽救治疗疗效高于 III 期临床试验，这可能是由于方案中加入了新的有效药物。这些结果增加了我们对马拉维若的疗效、安全性和处方条件的理解，超出了初始注册试验和早期制造商药物警戒计划。
