Risk of selecting resistance mutations during treatment interruption

To describe the evolution of drug-resistant mutations in patients undergoing treatment interruption strategies. We discuss potential predictors for selecting resistant mutations during treatment interruption.

Current studies on the evolution of drug-resistant mutations during treatment interruption show a low selection frequency for de-novo and archived mutations. The de-novo selection of resistant mutations increases when lamivudine or non-nucleoside reverse transcriptase inhibitor-containing regimens are withdrawn. Although treatment interruption in the context of failing antiretroviral therapy induces the selection of more drug-susceptible strains, resistant virus remains archived and re-emerges once therapy is re-administered, thus thwarting long-term clinical benefits. Alternatively, partial treatment interruption data support the evaluation of treatment strategies aimed at maintaining the benefit of therapy while reducing drug exposure.

The safety and efficiency of treatment interruption strategies remain controversial. The selection of new drug-resistance mutations during treatment interruption is not a key factor in accelerating disease progression when compared with continuous therapy. Conversely, reversion towards more drug-susceptible virus after treatment interruption in heavily treated patients may be accompanied by increased viral pathogenicity, and provides little clinical benefit in subsequent HIV-1 chemotherapy. Partial treatment interruption may be valuable in this context, but larger randomized clinical trials are needed.