Criteria for changing therapy include a suboptimal reduction in plasma viremia after initiation of therapy, re-appearance of viremia after suppression to undetectable, significant increases in plasma viremia from the nadir of suppression, and declining CD4+T cell numbers. When the decision to change therapy is based on viral load determination, it is, preferable to confirm with a second viral load test. Distinguish between the need to change regimen due to drug intolerance or inability to comply with the regimen versus failure to achieve the goal of sustained viral suppression; single agents can be changed or dose reduced in the event of drug intolerance.

In general, do not change a single drug or add a single drug to a failing regimen; it is important to use at least two new drugs and preferably to use an entirely new regimen with at lease three new drugs. Many patients have limited options for new regimens of desired potency; in some of these cases it is rational to continue the prior regimen if partial viral suppression was achieved.

In some cases, regimens identified as sub-optimal for initial therapy are rational due to limitations imposed by toxicity, intolerance or no-adherence. This especially applies in late stage disease. For patients with no rational alternative options who have virologic failure with return of viral load baseline (pretreatment levels) and declining CD4+T cell count, there should be consideration for discontinuation of antiretroviral therapy. Experience is limited with regimens using combinations of two protease inhibitors or combinations of protease inhibitors with Nevirapine and Delavirdine; for patient with limited options.