title: In vivo fitness cost of the M184V mutation in multidrug-resistant human immunodeficiency virus type 1 in the absence of lamivudine.
abstract: Lamivudine therapy selects for the M184V mutation. Although this mutation reduces the replicative capacity of human immunodeficiency virus in vitro, its impact on viral fitness in vivo has not been well defined. We used quantitative allele-specific PCR to precisely calculate the fitness differences between the mutated M184V virus and one that had reverted to the wild type in a cohort of patients by selectively interrupting reverse transcriptase inhibitor therapy, and we found that the M184V variants were consistently 4 to 8% less fit than the wild type in the absence of drug. After a lag phase of variable duration, wild-type variants emerged due to continued evolution of pol and back mutation rather than through emergence of an archived wild-type variant.
authors.affiliation: Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Roger
authors.initials: R
authors.lastname: Paredes
authors.forename: Manish
authors.initials: M
authors.lastname: Sagar
authors.forename: Vincent C
authors.initials: VC
authors.lastname: Marconi
authors.forename: Rebecca
authors.initials: R
authors.lastname: Hoh
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Martin
authors.forename: Neil T
authors.initials: NT
authors.lastname: Parkin
authors.forename: Christos J
authors.initials: CJ
authors.lastname: Petropoulos
authors.forename: Steven G
authors.initials: SG
authors.lastname: Deeks
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Kuritzkes
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology*; D024921:Drug Resistance, Multiple, Viral; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000145:classification / Q000187:drug effects / Q000235:genetics / Q000254:growth & development*; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology*; D020125:Mutation, Missense; D010802:Phylogeny; D017422:Sequence Analysis, DNA
chemical_list: D019380:Anti-HIV Agents; D019259:Lamivudine; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase