Campo Rafael E, Moreno Jose N, Suarez German, Miller Nancimae, Kolber Michael A, Holder Daniel J, Shivaprakash Malathi, DeAngelis Dana M, Wright Jennifer L, Schleif William A, Emini Emilio A, Condra Jon H
Department of Pathology, University of Miami School of Medicine, Florida, USA.
AIDS. 2003 Sep 5;17(13):1933-9. doi: 10.1097/00002030-200309050-00012.
To assess responses to indinavir (IDV)-ritonavir (RTV)-based regimens among HIV-1 infected patients with prior failure of protease inhibitors, and to assess the effects of adherence to therapy and pre-existing genotypic and phenotypic resistance on this response.
Twenty-eight patients initiating salvage regimens with IDV-RTV (800 mg and 200 mg twice daily, respectively) plus one or more reverse transcriptase inhibitor (RTI) were identified retrospectively. Genotypic and phenotypic susceptibilities to multiple antiretroviral agents were determined on viral samples collected at initiation of the salvage regimens, and adherence to therapy was determined through patient self-reporting. Response to therapy (viral RNA </= 400 copies/ml) was assessed at the end of and beyond 6 months of follow-up.
Based on responses measured in the first 6 months of follow-up, 16 responders and 12 non-responders were identified without differences in baseline demographic factors, laboratory parameters, extent of prior antiretroviral therapy, or characteristics of the RTI components of the new IDV-RTV-based regimens. Adequate adherence was associated with virologic responses (P = 0.005). There were trends for genotypic and phenotypic resistance to be associated with adequate adherence, and, surprisingly, phenotypic resistance to IDV was associated with virologic response rather than with therapeutic failure (P = 0.02). Beyond 6 months of follow-up (mean follow-up 69 weeks), adequate adherence was still associated with virologic response (P = 0.001), but genotypic or phenotypic resistance to IDV were not associated with therapeutic failure.
These results suggest that IDV-RTV-based regimens may be able to overcome IDV resistance. This underscores the importance of drug adherence, potency, and exposure in determining virologic responses to antiretroviral therapy.
评估在蛋白酶抑制剂曾治疗失败的HIV-1感染患者中，对基于茚地那韦（IDV）-利托那韦（RTV）方案的反应，并评估治疗依从性以及预先存在的基因型和表型耐药性对该反应的影响。
回顾性鉴定了28例开始采用IDV-RTV（分别为每日两次，每次800毫克和200毫克）加一种或多种逆转录酶抑制剂（RTI）进行挽救治疗方案的患者。在挽救治疗方案开始时收集的病毒样本上测定对多种抗逆转录病毒药物的基因型和表型敏感性，并通过患者自我报告确定治疗依从性。在随访6个月结束时及之后评估治疗反应（病毒RNA≤400拷贝/毫升）。
根据随访前6个月测得的反应，确定了16例反应者和12例无反应者，在基线人口统计学因素、实验室参数、既往抗逆转录病毒治疗程度或新的基于IDV-RTV方案的RTI成分特征方面无差异。充分依从性与病毒学反应相关（P = 0.005）。基因型和表型耐药性有与充分依从性相关的趋势，令人惊讶的是，对IDV的表型耐药性与病毒学反应相关而非治疗失败（P = 0.02）。随访6个月后（平均随访69周），充分依从性仍与病毒学反应相关（P = 0.001），但对IDV的基因型或表型耐药性与治疗失败无关。
这些结果表明基于IDV-RTV的方案可能能够克服IDV耐药性。这强调了药物依从性、效力和暴露量在确定抗逆转录病毒治疗的病毒学反应中的重要性。
