Sobering news emerged at the Third International workshop on Salvage Therapy for HIV-1 Infection (Chicago, IL, USA; April 12-14). Delegates heard that despite gains from widespread use of highly active antiretroviral therapy (HAART, rates of treatment failure remain high. Amanda Mocroft (Royal Free Centre for HIV Medicine, London, UK reported that rates of treatment failure in the EuroSIDA cohort were 50%, 70%, and 80% after first, second, and third courses, respectively.

Results from several trials confirmed the poor response (about 30%) to salvage regimens in patients who had already taken a protease inhibitor. Previous use of non-nucleoside reverse-transcriptase inhibitors lowered the response rate further (to about 15%). Robert Hogg (St Paul's Hospital, Vancouver, BC, Canada) reported that the experience of the treating physician was a strong, independent predictor of outcome. This is not surprising given the increasing complexities associated with the use of antiretroviral therapy.

Several strategies to improve the response to salvage therapy were proposed. These included avoidance of sequential monotherapy, use of resistance testing to select the most active regimen, and promotion of favourable drug interactions. Several studies supported the pharmacokinetic enhancement of protease inhibitors with low doses of ritonavir; same caution was expressed regarding the lack of long-term data on the safety of such combinations.

The authors of three separate observational studies reported on the use of drug regimens involving up to nine drugs. Because of the absence of controlled studies and the potential for serious drug toxicity such an approach was not recommended, however. Neither was strategic treatment interruption, because of safety concerns and the absence of data showing an improved response when treatment is restarted.

Of some concern was that, over the past year, the development of several promising drugs has been put on hold or stopped because of toxicity, unfavourable pharmacokinetics, and inadequate potency; presentations from key regulatory agenices underscored the need for innovative trial designs. Delegates agreed that the growing challenge of salvage therapy can be met only through the integrated and timely efforts of industry, government, and academia.