REATMENT OF HUMAN IMMUNOdeficiency virus type 1 (HIV-1) infection with highly active antiretroviral therapy (HAART) can suppress viremia to below the limit of detection of available clinical assays. 1-3 The current goal of antiretroviral therapy is suppression of viremia to below 50 copies/mL of HIV-1 RNA, the limit of detection of the most sensitive available clinical assay. 4,5 Suppression to this level is necessary to prevent drug resistance, the major cause of treatment failure. 6,7 After achieving suppression, many patients experience intermittent episodes of detectable viremia ("blips"). 8-16 Blips may raise concern that resistance is developing and complicate management by increasing patient anxiety, triggering costly repeat measurements of viral load, and generating uncertainty re

In vitro studies have shown that the host cytidine deaminase APOBEC3G causes lethal hypermutation in human immunodeficiency virus type 1 reverse transcripts unless its incorporation into virions is blocked by Vif. By examining stably archived sequences in resting CD4؉ T cells, we show that hypermutation occurs in most if not all infected individuals. Hypermutated sequences comprised >9% of archived species in resting CD4 ؉ T cells but were not found in plasma virus. Mutations occurred in predicted contexts, with notable hotspots. Thus, defects in Vif function in vivo give rise to hypermutated viral genomes that can be integrated but do not produce progeny viruses.