Rey D, Schmitt M P, Hess-Kempf G, Krantz V, Partisani M, Bernard-Henry C, Lang J M
CISIH, clinique médicale A, hôpitaux universitaires, 1, place de l'Hôpital, 67091 Strasbourg, France.
Pathol Biol (Paris). 2001 Sep;49(7):559-66. doi: 10.1016/s0369-8114(01)00211-5.
Structured therapeutic interruption (STI) has been offered to HIV-1 infected patients with virological failure (viral load > 1500 copies/mL) of potent antiretroviral therapy (ART) (three or four drugs for at least one year). CD4 lymphocyte count, HIV-1 viral load, clinical status, were assessed every month during STI and after ART reintroduction. Genotype analysis by plasma virus sequencing was done before and after treatment interruption. The results of 14 patients who resumed ART for at least two months are presented. Median duration of STI was 7.5 months (range: 2-13 months). Median CD4 count was low (45/mm3) when treatment was stopped, and decreased during STI (-37/mm3 after six months). Several patients exhibited important CD4 diminutions. Viral load slightly increased (+0.83 log at M6). Few clinical events occurred: one: severe HIV-related prurigo and one CMV viremia. Reversion of resistance mutations was only seen in 2/13 (15: 4%) patients (who had previously a major CD4 deficiency, and a long treatment history), a partial reversion occurred in 5/13 (38.5%) subjects, and the mutations didn't change in the other cases (genotyping non interpretable in the last patient). ART reintroduction induced a good immune response: CD4/mm3 after six months, with significant increases in 10/14 subjects. There was an initial viral response (median viral load: -2.34 log at M1), but a quick rebound most often occurred. However, viral load remained < 50 copies/mL in four patients. In conclusion, a rapid and important decline in CD4 cell count can occur when treatment is discontinued, in patients with virological failure of ART, but the clinical risk appears to be limited. Treatment re-initiation induces a good response, but virologically transient in most cases. Patients with a shift to wild-type virus seem to have a better response.
对于接受高效抗逆转录病毒治疗(ART)(使用三种或四种药物至少一年)出现病毒学失败(病毒载量>1500拷贝/毫升)的HIV-1感染患者,提供了结构化治疗中断(STI)。在STI期间和重新引入ART后,每月评估CD4淋巴细胞计数、HIV-1病毒载量和临床状况。在治疗中断前后通过血浆病毒测序进行基因型分析。呈现了14例重新开始ART至少两个月的患者的结果。STI的中位持续时间为7.5个月(范围:2 - 13个月)。停止治疗时CD4计数中位数较低(45/立方毫米),并且在STI期间下降(6个月后下降37/立方毫米)。几名患者出现了显著的CD4减少。病毒载量略有增加(M6时增加0.83对数)。很少发生临床事件:1例严重的HIV相关瘙痒症和1例巨细胞病毒血症。仅在2/13(15.4%)的患者中观察到耐药突变的逆转(这些患者先前有严重的CD4缺乏和较长的治疗史),5/13(38.5%)的受试者发生了部分逆转,在其他情况下突变未改变(最后1例患者基因分型无法解读)。重新引入ART诱导了良好的免疫反应:6个月后CD4/立方毫米,10/14的受试者显著增加。有初始病毒反应(M1时病毒载量中位数:-2.34对数),但最常出现快速反弹。然而,4例患者的病毒载量仍<50拷贝/毫升。总之,对于ART病毒学失败的患者,停止治疗时CD4细胞计数可能会迅速且显著下降,但临床风险似乎有限。重新开始治疗诱导了良好的反应,但在大多数情况下病毒学反应是短暂的。向野生型病毒转变的患者似乎反应更好。
Verh K Acad Geneeskd Belg. 2001
Scand J Infect Dis Suppl. 2003