ANTIRETROVIRAL THERAPY FOR HIV-INFECTION - A KNOWLEDGE-BASED APPROACHTO DRUG SELECTION AND USE

In the absence of evidence that eradication of HIV from an infected in dividual is feasible, the established goal of antiretroviral therapy i s to reduce viral load to as low as possible for as long as possible. Achieving this with the currently available antiretroviral agents invo lves appropriate selection of components of combination regimens to ob tain an optimal antiviral response. In addition, consideration of a pl an for a salvage or second-line regimen is required if initial therapy fails to achieve an optimal response or should loss of virological co ntrol occur despite effective initial therapy. Such a planned approach , based on consideration of the likely modes of therapeutic failure (v iral resistance, cellular resistance, toxicity) could be called ration al sequencing. Choice of therapy should never involve compromise in te rms of activity. However, the choice of drug should also be guided by tolerability profiles and considerations of coverage of the widest ran ge of infected cells, compartmental penetration, pharmacokinetic inter actions and, importantly, the ability of an agent or combination to li mit future therapeutic options through selection of cross-resistant vi rus. Available clinical end-point data clearly indicate that combinati on therapy is superior to monotherapy. with clinical and surrogate mar ker data supporting the use of triple drug (or double pretense inhibit or) combinations over double nucleoside analogue combinations. Thus. 3 -drug therapy, should represent current standard practice in a nontria ls setting. Treatment should be considered as early as practical, and may be best guided by measurement of. viral load, with a range of othe r markers having potential utility in individualism treatment decision s. 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 intolera nce may also be best managed by rational substitution.