Moyle G J, Gazzard B G, Cooper D A, Gatell J
Kobler Centre, Chelsea and Westminster Hospital, London, England.
Drugs. 1998 Mar;55(3):383-404. doi: 10.2165/00003495-199855030-00005.
In the absence of evidence that eradication of HIV from an infected individual is feasible, the established goal of antiretroviral therapy is to reduce viral load to as low as possible for as long as possible. Achieving this with the currently available antiretroviral agents involves appropriate selection of components of combination regimens to obtain an optimal antiviral response. In addition, consideration of a plan for a salvage or second-line regimen is required if initial therapy fails to achieve an optimal response or should loss of virological control occur despite effective initial therapy. Such a planned approach, based on consideration of the likely modes of therapeutic failure (viral resistance, cellular resistance, toxicity) could be called rational sequencing. Choice of therapy should never involve compromise in terms of activity. However, the choice of drug should also be guided by tolerability profiles and considerations of coverage of the widest range of infected cells, compartmental penetration, pharmacokinetic interactions and, importantly, the ability of an agent or combination to limit future therapeutic options through selection of cross-resistant virus. Available clinical end-point data clearly indicate that combination therapy is superior to monotherapy, with clinical and surrogate marker data supporting the use of triple drug (or double protease inhibitor) combinations over double nucleoside analogue combinations. Thus, 3-drug therapy should represent current standard practice in a nontrials setting. Treatment should be considered as early as practical, and may be best guided by measurement of viral load, with a range of other markers having potential utility in individualising treatment decisions. Therapeutic failure may be defined clinically, immunologically or, ideally, virologically, and should prompt substitution of at least 2, and preferably all, components of the treatment regimen. Drug intolerance may also be best managed by rational substitution.
在缺乏证据表明从感染个体中根除艾滋病毒可行的情况下，抗逆转录病毒疗法既定的目标是尽可能长时间地将病毒载量降至尽可能低的水平。使用目前可用的抗逆转录病毒药物实现这一目标需要适当选择联合治疗方案的组成部分，以获得最佳的抗病毒反应。此外，如果初始治疗未能达到最佳反应，或者尽管初始治疗有效但仍出现病毒学控制丧失的情况，则需要考虑制定挽救或二线治疗方案。这种基于考虑治疗失败的可能模式（病毒耐药性、细胞耐药性、毒性）的有计划的方法可称为合理排序。治疗的选择在活性方面绝不应妥协。然而，药物的选择还应以耐受性特征以及对最广泛感染细胞的覆盖范围、组织穿透性、药代动力学相互作用的考虑为指导，重要的是，一种药物或联合用药通过选择交叉耐药病毒限制未来治疗选择的能力。现有的临床终点数据清楚地表明，联合治疗优于单一治疗，临床和替代标志物数据支持使用三联药物（或双蛋白酶抑制剂）联合方案而非双核苷类似物联合方案。因此，在非试验环境中，三联药物治疗应代表当前的标准做法。治疗应尽早进行，最好以病毒载量测量为指导，一系列其他标志物在个体化治疗决策中可能有用。治疗失败可从临床、免疫学角度定义，理想情况下从病毒学角度定义，并且应促使至少更换治疗方案的2种，最好是所有组成部分。药物不耐受也最好通过合理替代来处理。
