The role of combinations of HIV protease inhibitors in the management of persons with HIV infection.

The current standard of care in antiretroviral therapy includes two nucleoside analogue reverse transcriptase inhibitors (NRTIs) plus a potent third agent, usually an HIV protease inhibitor (PI). However, around 20 - 30% of patients initiating therapy in clinical studies, and probably more in clinical practice, fail to achieve an optimal therapeutic response, a sustained undectectable viral load, using these regimens. Additionally, many triple therapy regimens currently require three times per day dosing, making treatment adherence difficult to sustain. Combinations of two PIs with or without NRTIs provide impressive reductions in viral load, with emerging data suggesting a higher proportion of patients on four drug regimens achieving below detection responses than those on three drug regimens. Additionally, pharmacokinetic interactions between PIs provide the potential for both dose reductions and twice daily dosing with PI combinations. However, limited resistance data are available from dual PI failures, and concerns regarding disturbances in fat metabolism, lipodystrophy and glucose intolerance remain obstacles to the widespread use of these regimens as initial therapy.