The use of protease inhibitors in resource-limited settings will increase in coming years as HIV treatment cohorts mature. We review data available to guide the expanded use of protease inhibitors in these settings.

The safety and effectiveness of protease inhibitors may be affected by the context of their use, yet limited data exist regarding the use of these agents in resource-limited settings in either first or subsequent regimens. Critically, data are needed regarding optimal regimens at time of first-line nonnucleoside reverse transcriptase inhibitor-based regimen failure. A number of alternative strategies are being investigated, including dual-boosting, monotherapy and dose reduction. Despite recent progress cost, storage requirements, drug interactions and formulation continue to hinder the use of protease inhibitors, particularly for children.

Protease inhibitors are the core component of second-line therapy in resource-limited settings and are used in specific situations in first-line therapy. Use of second-line regimens has been more diverse than first line, but WHO has recently prioritized regimens containing lopinavir/ritonavir or ritonavir-boosted atazanavir. As use of protease inhibitors in resource-limited settings increases evidence needs to be accrued to guide further expanded use.