Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents

NIH Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents

Table 13

Table 13. Guidelines for changing an antiretroviral regimen for suspected drug failure

Vol. 47 / No. RR-5 MMWR 79

Criteria for changing therapy include a suboptimal reduction in plasma viremia after initiation of therapy, reappearance of viremia after suppression to undetectable, substantial increases in plasma viremia from the nadir of suppression, and declining CD4 + T cell numbers. Refer to the more extensive discussion of these criteria in "Criteria for Changing Therapy" on pages 53-54.
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 a regimen because of 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 least 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 suboptimal for initial therapy are rational due to limitations imposed by toxicity, intolerance, or nonadherence. This especially applies in late-stage disease. For patients with no rational alternative options who have virologic failure with return of viral load to baseline (pretreatment levels) and a declining CD4+ T cell count, discontinuation of antiretroviral therapy should be considered.
Experience is limited with regimens using combinations of two protease inhibitors or combinations of protease inhibitors with nevirapine or delavirdine; for patients with limited options due to drug intolerance or suspected resistance, these regimens provide possible alternative treatment options.
There is limited information about the value of restarting a drug that the patient has previously received. The experience with zidovudine is that resistant strains are often replaced with "wild-type" zidovudine sensitive strains when zidovudine treatment is stopped, but resistance recurs rapidly if zidovudine is restarted. Although preliminary evidence indicates that this occurs with indinavir, it is not known if similar problems apply to other nucleoside analogues, protease inhibitors, or NNRTIs, but a conservative stance is that they probably do.
Avoid changing from ritonavir to indinavir or vice versa for drug failure, because high-level cross-resistance is likely.
Avoid changing from nevirapine to delavirdine or vice versa for drug failure, because high-level cross-resistance is likely.
The decision to change therapy and the choice of a new regimen require that the clinician have considerable expertise in the care of persons living with HIV infection. Physicians who are less experienced in the care of persons with HIV infection are strongly encouraged to obtain assistance through consultation with or referral to a clinician who has considerable expertise in the care of HIV-infected patients.