Raffi F, Reliquet V, Auger S, Besnier J M, Chennebault J M, Billaud E, Michelet C, Perre P, Lafeuillade A, May T, Billaudel S
Department of Infectious Diseases, University Hospital, Nantes, France.
AIDS. 1998 Oct 22;12(15):1999-2005. doi: 10.1097/00002030-199815000-00011.
To assess the efficacy, tolerance, and safety of combination antiretroviral therapy with didanosine and stavudine in HIV-infected patients with CD4+ cell counts > 100 x 10(6)/l and HIV plasma RNA > 10(4) copies/ml previously treated with other antiretroviral agents for at least 3 months.
In this open, multicentre, non-randomized, Phase II pilot study, adult patients were administered didanosine (200 mg twice daily) plus stavudine (40 mg twice daily) for 6 months. Patients for whom the first regimen had led to undetectable HIV RNA levels were offered a second 6-month course of treatment; those who had achieved insufficient immunological and virological gains in the first 6 months were given a new combination.
Primary evaluation of efficacy was based on viral load measured by branched DNA second-generation testing (lower limit of detection, 500 copies/ml) and CD4+ cell counts; secondary evaluations included AIDS-defining events and clinical side-effects.
Sixty-five patients with median prior antiretroviral therapy of 24 months (65 with zidovudine, 29 with zalcitabine) were included in the study. At baseline, median CD4+ cell count was 198 x 10(6)/l and median plasma HIV RNA was 80000 copies/ml (4.9 log10 copies/ml). In this heavily pretreated population, an increase in the mean CD4+ cell count was observed (+70 x 10(6)/l at 24 weeks). In addition, rapid and prolonged antiviral activity was seen, with a mean maximal decrease of 1.1 log10 copies/ml at week 4, a mean decrease of 0.89 log10 copies/ml at week 24, and a plasma RNA viraemia < 500 copies/ml achieved in 14% of patients at week 24.
Combination therapy with stavudine and didanosine is safe and leads to a sustained antiviral effect, even in patients with prolonged prior antiretroviral exposure and low CD4+ cell counts.
评估在接受其他抗逆转录病毒药物治疗至少3个月、CD4+细胞计数>100×10⁶/L且血浆HIV RNA>10⁴拷贝/ml的HIV感染患者中，去羟肌苷与司他夫定联合抗逆转录病毒疗法的疗效、耐受性及安全性。
在这项开放、多中心、非随机的II期试点研究中，成年患者接受去羟肌苷（每日两次，每次200mg）加司他夫定（每日两次，每次40mg）治疗6个月。对于首个治疗方案使HIV RNA水平降至检测不到的患者，提供第二个6个月疗程的治疗；在最初6个月免疫和病毒学改善不足的患者，给予新的联合治疗方案。
疗效的主要评估基于通过分支DNA第二代检测法测量的病毒载量（检测下限为500拷贝/ml）和CD4+细胞计数；次要评估包括艾滋病定义事件和临床副作用。
65例患者纳入研究，既往抗逆转录病毒治疗的中位时间为24个月（65例接受齐多夫定治疗，29例接受扎西他滨治疗）。基线时，CD4+细胞计数中位数为198×10⁶/L，血浆HIV RNA中位数为80000拷贝/ml（4.9 log₁₀拷贝/ml）。在这个经过大量治疗的人群中，观察到CD4+细胞计数平均值增加（24周时增加70×10⁶/L）。此外，观察到快速且持久的抗病毒活性，第4周时平均最大降幅为1.1 log₁₀拷贝/ml，第24周时平均降幅为0.89 log₁₀拷贝/ml，24周时14%的患者血浆RNA病毒血症<500拷贝/ml。
司他夫定与去羟肌苷联合治疗是安全的，并能产生持续的抗病毒效果，即使在既往长期接受抗逆转录病毒治疗且CD4+细胞计数较低的患者中也是如此。
