title: Short Communication: In Vitro Accumulation of Drug Resistance Mutations in Chimeric Infectious Clones Containing Subtype B or C Reverse Transcriptase and Selected with Tenofovir or Didanosine.
abstract: Highly active antiretroviral therapy (HAART) contributed to the improvement in the life expectancy of HIV-infected patients. However, the emergence of drug-resistant mutations (DRM) is a major viral factor impacting therapeutic failure. Differences in DRM can occur among HIV-1 subtypes. We evaluate the kinetics of the selection of resistance mutations in vitro analyzing two chimeric clones that contain the reverse transcriptases of subtypes B or C (RTB' and RTC') in cells treated with increasing concentrations of tenofovir disoproxil fumarate (TDF) and didanosine (ddI). The mutation K65R is selected more quickly in RTC' than in RTB' viruses with TDF and ddI, and additional mutations (positions 45, 62, and 68) were selected after K65R fixation. Other primary mutations (M184V and Q151M) were selected with ddI treatment in conjunction with K65R only in RTC' viruses. Both patterns, M184V+K65R and Q151M+K65R, have a significant impact on NRTI resistance. Our data suggest that selection of TDF and ddI DRMs can occur earlier in subtype C HIV in patients when compared to subtype B.
authors.affiliation: 1 Laboratório de Virologia Molecular, Universidade Federal do Rio de Janeiro , Rio de Janeiro, Rio de Janeiro, Brazil .
authors.forename: Rodrigo D
authors.initials: RD
authors.lastname: Cunha
authors.affiliation: 1 Laboratório de Virologia Molecular, Universidade Federal do Rio de Janeiro , Rio de Janeiro, Rio de Janeiro, Brazil .
authors.forename: Celina M
authors.initials: CM
authors.lastname: Abreu
authors.affiliation: 1 Laboratório de Virologia Molecular, Universidade Federal do Rio de Janeiro , Rio de Janeiro, Rio de Janeiro, Brazil .
authors.forename: Arielly K P
authors.initials: AK
authors.lastname: Sousa
authors.affiliation: 1 Laboratório de Virologia Molecular, Universidade Federal do Rio de Janeiro , Rio de Janeiro, Rio de Janeiro, Brazil .
authors.forename: Viviana C J
authors.initials: VC
authors.lastname: Mabombo
authors.affiliation: 2 Department of Virology, Medical Microbiology, University Medical Center Utrecht , Utrecht, the Netherlands .
authors.forename: Monique
authors.initials: M
authors.lastname: Nijhuis
authors.affiliation: 2 Department of Virology, Medical Microbiology, University Medical Center Utrecht , Utrecht, the Netherlands .
authors.forename: Dorien
authors.initials: D
authors.lastname: de Jong
authors.affiliation: 1 Laboratório de Virologia Molecular, Universidade Federal do Rio de Janeiro , Rio de Janeiro, Rio de Janeiro, Brazil .
authors.forename: Amilcar
authors.initials: A
authors.lastname: Tanuri
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology*; D016049:Didanosine / Q000494:pharmacology*; D024882:Drug Resistance, Viral; D005838:Genotype; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000145:classification / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D006801:Humans; D059645:Mutation Rate; D020125:Mutation, Missense; D012692:Serial Passage; D000068698:Tenofovir / Q000494:pharmacology*
chemical_list: D019380:Anti-HIV Agents; D000068698:Tenofovir; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D016049:Didanosine