Deeks S G, Grant R M, Beatty G W, Horton C, Detmer J, Eastman S
University of California, San Francisco and San Francisco General Hospital, 94110, USA.
AIDS. 1998 Jul 9;12(10):F97-102. doi: 10.1097/00002030-199810000-00002.
To evaluate the virologic activity of a ritonavir plus saquinavir-containing regimen in patients who have failed an indinavir or ritonavir-containing regimen.
Patients were identified through a retrospective study evaluating the incidence of indinavir or ritonavir failure in our clinic.
Eighteen patients failing indinavir or ritonavir therapy and who switched to a ritonavir-saquinavir-containing regimen were evaluated. Indinavir or ritonavir failure was defined as a plasma viral load > 1500 copies/ml (branched DNA) after 16 weeks of continuous therapy.
All patients switched to ritonavir (400 mg twice daily) plus saquinavir (400 mg twice daily) and received concurrent therapy with two nucleoside reverse transcriptase inhibitors (NRTI). Twelve of the 18 patients modified their NRTI regimen at the time ritonavir-saquinavir was initiated.
Plasma viral load was monitored using a branched DNA assay. Genotypic analysis was performed using a point mutation differential hybridization technique, and was confirmed with direct sequencing.
Fourteen out of 18 patients completed at least 24 weeks of therapy; the remaining four patients discontinued therapy after week 12 due to a lack of virologic response or intolerance. Plasma viral load decreased a median 1.4 log10 after 4 weeks of treatment with ritonavir-saquinavir. Only four patients had a greater than 0.5 log10 decrease in viral load after 24 weeks of therapy. In eight out of 10 patients evaluated, the V82A mutation was present at the time of the switch to ritonavir-saquinavir. Viral rebound on ritonavir-saquinavir was associated with the emergence of mutations at amino acids 46, 48, 54 and 90.
The combination of ritonavir, saquinavir and two NRTI resulted in a moderate but transient suppression of viral replication in patients who have failed indinavir or ritonavir therapy. Failure of ritonavir-saquinavir may be associated with the emergence of mutations associated with resistance to ritonavir/saquinavir monotherapy, particularly the L90M mutation.
评估含利托那韦和沙奎那韦的治疗方案对接受茚地那韦或含利托那韦治疗方案失败患者的病毒学活性。
通过一项回顾性研究确定患者，该研究评估了我们诊所中茚地那韦或利托那韦治疗失败的发生率。
对18例茚地那韦或利托那韦治疗失败且转而接受含利托那韦 - 沙奎那韦治疗方案的患者进行评估。茚地那韦或利托那韦治疗失败定义为连续治疗16周后血浆病毒载量>1500拷贝/毫升（分支DNA法）。
所有患者转而接受利托那韦（每日两次，每次400毫克）加沙奎那韦（每日两次，每次400毫克），并同时接受两种核苷类逆转录酶抑制剂（NRTI）治疗。18例患者中有12例在开始使用利托那韦 - 沙奎那韦时调整了他们的NRTI治疗方案。
使用分支DNA分析法监测血浆病毒载量。采用点突变差异杂交技术进行基因分型分析，并通过直接测序进行确认。
18例患者中有14例完成了至少24周的治疗；其余4例患者在第12周后因缺乏病毒学反应或不耐受而停止治疗。使用利托那韦 - 沙奎那韦治疗4周后，血浆病毒载量中位数下降1.4 log10。治疗24周后，只有4例患者的病毒载量下降超过0.5 log10。在接受评估的10例患者中有8例在转而使用利托那韦 - 沙奎那韦时存在V82A突变。利托那韦 - 沙奎那韦治疗后病毒反弹与46、48、54和90位氨基酸处的突变出现有关。
利托那韦、沙奎那韦与两种NRTI联合使用，在茚地那韦或利托那韦治疗失败的患者中导致了对病毒复制的中度但短暂的抑制。利托那韦 - 沙奎那韦治疗失败可能与对利托那韦/沙奎那韦单药治疗耐药相关的突变出现有关，特别是L90M突变。
