Risk of selecting resistance mutations during treatment interruption

PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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resistant mutations increases when lamivudine or non-nucleoside reverse transcriptase inhibitor-containing regimens are withdrawn.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. SUMMARY: 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.