Rutschmann O T, Opravil M, Iten A, Malinverni R, Vernazza P L, Bucher H C, Bernasconi E, Sudre P, Leduc D, Yerly S, Perrin L H, Hirschel B
University Hospital, Geneva, Switzerland.
AIDS. 1998 May 28;12(8):F71-7. doi: 10.1097/00002030-199808000-00003.
To explore the short-term effects on surrogate markers for HIV progression of didanosine (ddl) plus stavudine (d4T), with or without hydroxyurea.
Randomized, double-blinded, prospective study.
Swiss HIV Cohort Study.
A total of 144 patients (75% antiretroviral-naive) were studied (mean baseline HIV-1 RNA, 4.53 log10 copies/ml; mean CD4 cell count, 370 x 10(6)/l).
Patients received ddl (200 mg twice daily) plus d4T (40 mg twice daily), with additional hydroxyurea (500 mg twice daily) or placebo.
The primary endpoint was a reduction of viraemia below 200 copies/ml after 12 weeks. At that time, patients who did not reach the primary endpoint were withdrawn in the hydroxyurea arm, whereas patients in the placebo group had the option of adding hydroxyurea to ddl and d4T. All patients were followed until week 24.
After 12 weeks, 54% of the patients randomized to hydroxyurea had viraemia below 200 copies/ml, compared with 28% on placebo (P < 0.001). Using an ultrasensitive assay with a limit of detection of 20 copies/ml, 19% of patients receiving hydroxyurea had viraemia levels below 20 copies/ml, compared with 8% on placebo (P = 0.05). Mean decrease in HIV-1 RNA was 2.3 and 1.7 log10 copies/ml for hydroxyurea and placebo groups, respectively (P = 0.001). Hydroxyurea was found to induce lymphopenia (-124 x 10(6)/l). Increase in CD4 cell counts was +28 x 10(6)/l during hydroxyurea treatment compared with +107 x 10(6)/l on placebo (P = 0.001).
Hydroxyurea improved the antiviral activity of d4T and ddl over a 12-week period, but was associated with a smaller increase in CD4 cell counts due to hydroxyurea-induced lymphopenia.
探讨去羟肌苷（ddI）加司他夫定（d4T），无论有无羟基脲，对HIV病情进展替代指标的短期影响。
随机、双盲、前瞻性研究。
瑞士HIV队列研究。
共研究了144例患者（75%为初治抗逆转录病毒治疗患者）（基线HIV-1 RNA平均为4.53 log10拷贝/ml；CD4细胞计数平均为370×10⁶/l）。
患者接受ddI（每日2次，每次200mg）加d4T（每日2次，每次40mg），加用羟基脲（每日2次，每次500mg）或安慰剂。
主要终点为12周后病毒血症降至200拷贝/ml以下。此时，未达到主要终点的患者在羟基脲组退出研究，而安慰剂组患者可选择在ddI和d4T基础上加用羟基脲。所有患者随访至24周。
12周后，随机分组至羟基脲组的患者中有54%病毒血症低于200拷贝/ml，而安慰剂组为28%（P<0.001）。采用检测限为20拷贝/ml的超敏检测方法，接受羟基脲治疗的患者中有19%病毒血症水平低于20拷贝/ml，而安慰剂组为8%（P=0.05）。羟基脲组和安慰剂组HIV-1 RNA平均下降分别为2.3和1.7 log10拷贝/ml（P=0.001）。发现羟基脲可导致淋巴细胞减少（-124×10⁶/l）。与安慰剂组（+107×10⁶/l）相比，羟基脲治疗期间CD4细胞计数增加为+28×10⁶/l（P=0.001）。
在12周期间，羟基脲可改善d4T和ddI的抗病毒活性，但由于羟基脲诱导的淋巴细胞减少，其导致CD4细胞计数增加较少。
