title: Comparison of resistance mutation patterns in historical plasma HIV RNA genotypes with those in current proviral HIV DNA genotypes among extensively treated patients with suppressed replication.
abstract: OBJECTIVE
  Heavily treatment-experienced patients with good virological control could be at risk of virological failure on switching to a new regimen if pre-existing drug resistance is not taken into account. We examined whether genotyping based on cellular HIV-1 DNA during controlled viraemia identifies resistance mutations detected in plasma HIV-1 RNA during treatment with previous antiretroviral regimens.
  
  
  METHODS
  All 169 patients enrolled in the Agence Nationale de Recherche sur le SIDA (ANRS) 138-intEgrase inhibitor MK_0518 to Avoid Subcutaneous Injections of EnfuviRtide (EASIER) trial had already received three antiretroviral drug classes [nucleoside reverse transcriptase inhibitor (NRTI), nonnucleoside reverse transcriptase inhibitor (NNRTI) and protease inhibitor (PI)] and had plasma HIV-1 RNA<400 copies/ml at baseline. The results of previous resistance genotyping of plasma HIV-1 RNA in individual patients were compared with those of resistance genotyping of whole-blood HIV-1 DNA at randomization.
  
  
  RESULTS
  A median of 4 plasma RNA genotypes were available for the 169 patients. The median numbers of resistance mutations in HIV-1 RNA and DNA were, respectively, 5 and 4 for NRTIs, 2 and 1 for NNRTIs, and 10 and 8 for PIs. The difference was significant for all three drug classes (P=0.001). Resistance to at least one antiretroviral drug was detected exclusively in HIV-1 RNA or in DNA in 63% and 13% of patients for NRTI, 47% and 1% of patients for NNRTI, and 50% and 7% of patients for PI, respectively.
  
  
  CONCLUSIONS
  This study shows that, among highly treatment-experienced patients on effective highly active antiretroviral therapy, resistance genotyping of HIV-1 DNA detects fewer resistance mutations than previous analyses of HIV-1 RNA. These results have implications for patient management and for the design of switch studies.
authors.affiliation: Virology Department, Saint-Louis Hospital-APHP, Inserm U941-Paris 7 Diderot University, Paris, France. constance.delaugerre@sls.aphp.fr
authors.forename: C
authors.initials: C
authors.lastname: Delaugerre
authors.forename: J
authors.initials: J
authors.lastname: Braun
authors.forename: I
authors.initials: I
authors.lastname: Charreau
authors.forename: S
authors.initials: S
authors.lastname: Delarue
authors.forename: M L
authors.initials: ML
authors.lastname: Nere
authors.forename: N
authors.initials: N
authors.lastname: de Castro
authors.forename: T
authors.initials: T
authors.lastname: May
authors.forename: B
authors.initials: B
authors.lastname: Marchou
authors.forename: F
authors.initials: F
authors.lastname: Simon
authors.forename: J M
authors.initials: JM
authors.lastname: Molina
authors.forename: J P
authors.initials: JP
authors.lastname: Aboulker
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology; D019380:Anti-HIV Agents / Q000494:pharmacology*; D018791:CD4 Lymphocyte Count; D004279:DNA, Viral / Q000187:drug effects / Q000235:genetics*; D024882:Drug Resistance, Viral / Q000187:drug effects / Q000235:genetics*; D005260:Female; D005838:Genotype; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D012367:RNA, Viral / Q000187:drug effects / Q000235:genetics*; D014779:Virus Replication / Q000187:drug effects / Q000235:genetics*
chemical_list: D019380:Anti-HIV Agents; D004279:DNA, Viral; D012367:RNA, Viral