接受茚地那韦、齐多夫定和拉米夫定联合治疗的HIV-1感染患者病毒学和临床结局的预测因素。艾滋病临床试验组方案320。

Predictors of virologic and clinical outcomes in HIV-1-infected patients receiving concurrent treatment with indinavir, zidovudine, and lamivudine. AIDS Clinical Trials Group Protocol 320.

作者信息

Demeter L M, Hughes M D, Coombs R W, Jackson J B, Grimes J M, Bosch R J, Fiscus S A, Spector S A, Squires K E, Fischl M A, Hammer S M

机构信息

Infectious Diseases Unit, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Box 689, Rochester, NY 14642, USA.

出版信息

Ann Intern Med. 2001 Dec 4;135(11):954-64. doi: 10.7326/0003-4819-135-11-200112040-00007.

DOI:10.7326/0003-4819-135-11-200112040-00007

PMID:11730396

Abstract

BACKGROUND

A substantial proportion of patients with HIV infection will not respond to antiretroviral therapy. Early predictors of response to treatment are needed to identify patients who are at risk for treatment failure.

OBJECTIVE

To determine predictors of virologic and clinical response to indinavir, zidovudine, and lamivudine therapy.

DESIGN

Observational analysis of one treatment group in a phase III trial.

SETTING

40 AIDS Clinical Trials units.

PATIENTS

489 patients receiving indinavir, zidovudine, and lamivudine who had 1) a CD4 count of 0.200 x 10(9) cells/L or less after 8 or more weeks of study therapy and 2) plasma HIV-1 RNA measurements obtained at baseline and week 8.

MEASUREMENTS

HIV-1 RNA level and CD4 cell count at weeks 0, 4, 8, 24, and 40. Clinical progression was defined as a new AIDS-defining illness or death.

RESULTS

Patients' levels of HIV-1 RNA at the 8th study week of therapy predicted whether patients would achieve virologic suppression to below 500 (or 50) copies/mL at study week 24. An HIV-1 RNA level less than 500 copies/mL at week 24 was achieved in 71% of patients whose level at week 8 had been less than 500 copies/mL, 53% of those with a level of 500 copies/mL or more and at least 2-log(10) copies/mL reduction since baseline, 29% of those with a level of 500 copies/mL or more with a 1- to 1.99-log(10) copies/mL reduction, and 9% of those with a level of 500 copies/mL or greater and less than 1-log(10) copies/mL reduction since baseline (P < 0.001). HIV-1 RNA level at week 8 also predicted clinical progression. HIV-1 disease progressed in 2.2% of the patients with a week-8 HIV-1 RNA level less than 500 copies/mL, 2.3% of patients with 500 copies/mL or greater and at least 2-log(10) copies/mL reduction since baseline, 4.9% of patients with 500 copies/mL or greater and 1- to 1.99-log(10) copies/mL reduction since baseline, and 10.6% of patients with 500 copies/mL or greater and less than 1-log(10) copies/mL decrease since baseline (P = 0.009). After adjustment for HIV-1 RNA level, patients with a higher week-8 CD4 cell count were more likely to have a week-24 HIV-1 RNA level less than 500 copies/mL (relative risk for patients with a week-8 CD4 count >/= 0.10 x 10(9) cells/L, 1.47 [95% CI, 1.00 to 2.16] compared with <0.050 x 10(9) cells/L; relative risk for patients with a week-8 CD4 count of 0.05 to 0.099 x 10(9) cells/L, 0.98 [CI, 0.61 to 1.57] compared with <0.050 x 10(9) cells/L). After adjustment for HIV-1 RNA level, patients with a week-8 CD4 count of 0.05 x 10(9) cells/L or greater (compared with <0.05 x 10(9) cells/L) had a decreased hazard for clinical progression (hazard ratio, 0.25 [CI, 0.09 to 0.67]).

CONCLUSIONS

The HIV-1 RNA level and CD4 cell count achieved at 8 weeks of treatment are important predictors of subsequent virologic and clinical outcomes.

摘要

背景

相当一部分感染HIV的患者对抗逆转录病毒治疗无反应。需要早期治疗反应预测指标来识别有治疗失败风险的患者。

目的

确定茚地那韦、齐多夫定和拉米夫定治疗的病毒学和临床反应预测指标。

设计

对一项III期试验中一个治疗组的观察性分析。

地点

40个艾滋病临床试验单位。

患者

489例接受茚地那韦、齐多夫定和拉米夫定治疗的患者，这些患者在研究治疗8周或更长时间后1）CD4细胞计数为0.200×10⁹细胞/L或更低，且2）在基线和第8周进行了血浆HIV-1 RNA测量。

测量指标

第0、4、8、24和40周时的HIV-1 RNA水平和CD4细胞计数。临床进展定义为出现新的艾滋病定义疾病或死亡。

结果

治疗第8周时患者的HIV-1 RNA水平可预测患者在研究第24周时是否能实现病毒学抑制至低于500（或50）拷贝/mL。第24周时HIV-1 RNA水平低于500拷贝/mL的患者中，71%在第8周时的水平低于500拷贝/mL，53%在第8周时水平为500拷贝/mL或更高且自基线以来至少降低2-log₁₀拷贝/mL，29%在第8周时水平为500拷贝/mL或更高且降低1至1.99-log₁₀拷贝/mL，9%在第8周时水平为500拷贝/mL或更高且自基线以来降低小于1-log₁₀拷贝/mL（P<0.001）。第8周时的HIV-1 RNA水平也可预测临床进展。第8周时HIV-1 RNA水平低于500拷贝/mL的患者中2.2%出现HIV-1疾病进展，第8周时水平为500拷贝/mL或更高且自基线以来至少降低2-log₁₀拷贝/mL的患者中2.3%出现进展，第8周时水平为500拷贝/mL或更高且降低1至1.99-log₁₀拷贝/mL的患者中4.9%出现进展，第8周时水平为500拷贝/mL或更高且自基线以来降低小于1-log₁₀拷贝/mL的患者中10.6%出现进展（P = 0.009）。在调整HIV-1 RNA水平后，第8周CD4细胞计数较高的患者在第24周时HIV-1 RNA水平低于500拷贝/mL的可能性更大（第8周CD4细胞计数≥0.10×10⁹细胞/L的患者与<0.050×10⁹细胞/L的患者相比，相对风险为1.47[95%CI，1.00至2.16]；第8周CD4细胞计数为0.05至0.099×10⁹细胞/L的患者与<0.050×10⁹细胞/L的患者相比，相对风险为0.98[CI，0.61至1.57]）。在调整HIV-1 RNA水平后，第8周CD4细胞计数为0.05×10⁹细胞/L或更高（与<0.05×10⁹细胞/L相比）的患者临床进展风险降低（风险比，0.25[CI，0.09至0.67]）。