Barreiro Pablo, de Mendoza Carmen, Camino Nuria, García-Benayas Teresa, Blanco Francisco, Núñez Marina, González-Lahoz Juan, Soriano Vincent
Service of Infectious Diseases, Hospital Carlos III, Madrid, Spain.
HIV Clin Trials. 2003 Nov-Dec;4(6):361-71. doi: 10.1310/4GMU-AG3T-Q3CC-GE5D.
Toxicity and quality of life issues have moved to delay the initiation of highly active antiretroviral therapy (HAART) and to explore novel treatment strategies for HIV infection. The switch to simpler regimens or treatment discontinuation has been attempted with limited success. The combination of hydroxyurea (HU) plus didanosine (ddI) is a simple regimen that might be able to restrain virus replication for long periods of time and could be an acceptable option as maintenance therapy in patients on prolonged successful HAART.
The combination of HU (500 mg bid) plus ddI (400 mg qd) was offered to participants with viral load (VL) <50 HIV RNA copies/mL and CD4 counts >350 cells/microL for more than 6 months under HAART. The prior HAART regimen was resumed if VL rose to >5,000 copies/mL and/or the CD4 count fell to <200 cells/microL after being on HU + ddI maintenance therapy.
A total of 187 participants replaced HAART with HU + ddI. In an intent-to-treat analysis at 48 weeks, 109 (58%) and 77 (41%) patients had VL below 5,000 and 500 HIV RNA copies/mL, respectively. The mean CD4 count dropped from 809 +/- 283 to 573 +/- 270 cells/microL, while 77% of patients remained above 350 cells/microL. The proportion of participants with hypercholesterolemia declined from 70% to 46% (p <.001), while those with hypertriglyceridemia fell from 36% to 21% (p <.05). Significant improvements in lipohypertrophy and lipoatrophy were observed in 52% and 64% of participants, respectively. Grade 3-4 toxicities appeared in 20 patients (11%), including 3 cases of pancreatitis and 1 of peripheral neuropathy. Prior history of VL >5 log, CD4 counts <200 cells/microL, and ddI experience were independently associated with lower response to HU + ddI maintenance therapy.
The combination of HU + ddI may be a satisfactory maintenance therapy for more than half of patients on successful HAART who want to alleviate drug-related toxicities and/or pill burden. Patients with metabolic and/or body-shape abnormalities might particularly benefit from switching to this simple regimen.
毒性和生活质量问题已导致高效抗逆转录病毒治疗（HAART）的启动延迟，并促使人们探索针对HIV感染的新型治疗策略。尝试改用更简单的治疗方案或停止治疗，但成效有限。羟基脲（HU）加去羟肌苷（ddI）的联合用药是一种简单的治疗方案，可能能够长时间抑制病毒复制，并且作为长期成功接受HAART治疗患者的维持治疗方案可能是一个可接受的选择。
向在HAART治疗下病毒载量（VL）<50拷贝/mL且CD4细胞计数>350个/微升超过6个月的参与者提供HU（500毫克，每日两次）加ddI（400毫克，每日一次）的联合用药。如果在接受HU + ddI维持治疗后VL升至>5000拷贝/mL和/或CD4细胞计数降至<200个/微升，则恢复之前的HAART治疗方案。
共有187名参与者用HU + ddI替代了HAART。在48周的意向性分析中，分别有109名（58%）和77名（41%）患者的VL低于5000和500拷贝/mL。平均CD4细胞计数从809±283降至573±270个/微升，而77%的患者仍高于350个/微升。高胆固醇血症患者的比例从70%降至46%（p<.001），而高甘油三酯血症患者的比例从36%降至21%（p<.05）。分别有52%和64%的参与者出现脂肪代谢障碍和脂肪萎缩有显著改善。20名患者（11%）出现3 - 4级毒性反应，包括3例胰腺炎和1例周围神经病变。既往VL>5 log、CD4细胞计数<200个/微升以及有ddI用药史与对HU + ddI维持治疗的反应较低独立相关。
对于超过半数希望减轻药物相关毒性和/或服药负担的成功接受HAART治疗的患者，HU + ddI联合用药可能是一种令人满意的维持治疗方案。有代谢和/或体型异常的患者可能特别受益于改用这种简单的治疗方案。
