Maggiolo Franco, Ripamonti Diego, Torti Carlo, Arici Claudio, Antinori Andrea, Quiros-Roldan Eugenia, Minoli Lorenzo, Sighinolfi Laura, Nasta Paola, Suter Fredy
Divisione di Malattie Infettive, Ospedali Riuniti, Bergamo, Italy.
Antivir Ther. 2006;11(7):923-9.
One of the more vigorous debates in the field of highly active antiretroviral therapy (HAART) is how to start it and what the optimal drug sequence is.
A retrospective cohort analysis was performed. The aim was to evaluate which variables could influence the virological response to second-line genotypic-based HAART in patients with virological documented first-line HAART failure. A positive response was defined as a confirmed HIV RNA level < 50 copies/ml.
Two hundred and eight patients were included. Demographic characteristics, risk factors for HIV acquisition, and drugs included in the initial treatment did not significantly influence the considered outcome. According to a multiple logistic model, the presence of thymidine analogue mutations (TAMs) had a negative association with the virological outcome (P = 0.006), whereas the use of a boosted protease inhibitor (PI) in second-line HAART was positively associated with the endpoint (P = 0.001). Patients receiving a genotypic-based second-line HAART containing a boosted PI achieved a viral load < 50 copies/ml in a 74.2% of cases compared with 52.2% of those whose therapy did not contain a boosted PI. This difference was statistically significant (P = 0.002) with an odds ratio (OR) of 2.63 and a 95% confidence interval (CI) ranging from 1.46 to 4.76. This last variable positively influenced the outcome even when the analysis was restricted to patients harbouring a virus presenting TAMs. In this case, second-line HAART was successful in 66.7% of cases with an OR of 3.25 and a 95% CI ranging from 1.28 to 8.25 (P = 0.014).
the wider range of available therapeutic options has made resistance and drug-sequencing considerations a crucial point in selecting first-line HAART. Our data indicate that, by limiting the risk of selecting or accumulating TAMs, it could be possible to save further therapeutic options. In second-line regimens, the higher antiviral effect and genetic barrier of boosted PIs may overcome the limits of the use of NRTI backbones, which retain only a partial effectiveness.
在高效抗逆转录病毒疗法（HAART）领域，较为激烈的争论之一是如何启动该疗法以及最佳的药物顺序是什么。
进行了一项回顾性队列分析。目的是评估哪些变量会影响病毒学记录显示一线HAART治疗失败的患者对基于基因型的二线HAART的病毒学反应。阳性反应定义为确诊的HIV RNA水平<50拷贝/毫升。
纳入了208名患者。人口统计学特征、HIV感染的危险因素以及初始治疗中使用的药物对所考虑的结果没有显著影响。根据多元逻辑模型，胸苷类似物突变（TAMs）的存在与病毒学结果呈负相关（P = 0.006），而在二线HAART中使用增强型蛋白酶抑制剂（PI）与终点呈正相关（P = 0.001）。接受包含增强型PI的基于基因型的二线HAART的患者，74.2%的病例实现了病毒载量<50拷贝/毫升，而治疗中不包含增强型PI的患者这一比例为52.2%。这种差异具有统计学意义（P = 0.002），优势比（OR）为2.63，95%置信区间（CI）为1.46至4.76。即使将分析局限于携带TAMs病毒的患者，最后这个变量对结果仍有积极影响。在这种情况下，二线HAART在66.7%的病例中取得成功，OR为3.25，95%CI为1.28至8.25（P = 0.014）。
可用治疗方案的范围更广，使得耐药性和药物顺序的考虑成为选择一线HAART的关键因素。我们的数据表明，通过限制选择或积累TAMs的风险，有可能保留更多的治疗选择。在二线治疗方案中，增强型PI更高的抗病毒效果和遗传屏障可能克服仅保留部分有效性的核苷类逆转录酶抑制剂（NRTI）主干使用的局限性。
