Rockstroh J K, Altfeld M, Kupfer B, Kaiser R, Fätkenheuer G, Salzberger B, Schneweis K E, Spengler U
Department of Medicine, Sigmund-Freud-Strasse 25, D-53105 Bonn, Germany.
Eur J Med Res. 1999 Jul 28;4(7):271-4.
A therapeutic dilemma arises once HIV-infected patients develop a break-through of HIV-replication under potent antiretroviral therapy. Therefore, we studied whether patients (n = 12) who failed double nucleoside reverse transcriptase (NRTI) plus indinavir or ritonavir triple therapy can be rescued when therapy is switched to double protease inhibitor (PI) treatment (nelfinavir and hard gel saquinavir) and stavudine. With the rescue regimen HIV-RNA levels initially dropped from 148,571 +/- 45,258 copies/ml to 9,310 +/- 6, 965 copies/ml at week 4 (p = 0.0117). However, virus load subsequently increased to almost baseline levels (131,230 +/- 37,743 copies/ml) at week 12. Likewise, CD4-cell counts could only be stabilized initially (baseline 267 +/- 51; week 4 296 +/- 65 cells/microl), but gradually declined thereafter (216 +/- 34 cells/microl week 12). Before therapy was switched, the viral protease gene from 5 analyzed patients showed 3-5 amino acid substitutions. Moreover, 4 of these patients had one amino acid substitution associated with resistance to nelfinavir. Our data suggest that HIV-infected patients resistant to indinavir or ritonavir and double NRTI combination therapy respond to double PI nelfinavir/saquinavir and D4T rescue therapy only initially but have no sustained benefit.
一旦感染HIV的患者在高效抗逆转录病毒治疗下出现HIV复制突破，就会产生治疗困境。因此，我们研究了接受双核苷类逆转录酶（NRTI）加茚地那韦或利托那韦三联疗法失败的患者（n = 12），在治疗转换为双蛋白酶抑制剂（PI）治疗（奈非那韦和硬明胶沙奎那韦）和司他夫定后是否能够得到挽救。采用挽救方案后，HIV-RNA水平最初在第4周从148,571±45,258拷贝/毫升降至9,310±6,965拷贝/毫升（p = 0.0117）。然而，病毒载量随后在第12周增加至几乎基线水平（131,230±37,743拷贝/毫升）。同样，CD4细胞计数最初只能得到稳定（基线267±51；第4周296±65个细胞/微升），但此后逐渐下降（第12周216±34个细胞/微升）。在治疗转换前，对5例分析患者的病毒蛋白酶基因检测显示有3 - 5个氨基酸替换。此外，这些患者中有4例有一个与对奈非那韦耐药相关的氨基酸替换。我们的数据表明，对茚地那韦或利托那韦以及双NRTI联合治疗耐药的HIV感染患者仅在最初对双PI奈非那韦/沙奎那韦和司他夫定挽救治疗有反应，但没有持续的益处。
