Despite antiretroviral therapy (ART), a latent reservoir of replication-competent HIV-1 persists in resting memory CD4 + T-cells and precludes cure 1-6 . Lorenzo-Redondo et al . 7 analyzed HIV-1 sequences collected from three individuals during the first six months of ART, discovered specific patterns of sequence evolution, and concluded that viral replication persists during therapy. We believe these evolutionary patterns are artifacts of rapidly decaying viral subpopulations present during the first months of therapy and are not characteristic of the long-lived reservoir. The study therefore provides no evidence that ongoing replication is an additional barrier to cure for treated individuals who consistently maintain low viral loads.