title: Baseline HIV type 1 genotypic resistance to a newly added nucleoside analog is predictive of virologic failure of the new therapy.
abstract: We evaluated the predictive value of baseline HIV-1 genotypic resistance mutations for failure of a nucleoside reverse transcriptase inhibitor (NRTI) containing therapy. The change in therapy of 88 HIV-1-infected patients was analyzed retrospectively, relating the genotypic resistance profile at baseline to the evolution of viral load and CD4+ T cell counts. Genotypic resistance at baseline and at 6 months was evaluated with the LiPA HIV-1 RT, which detects mutations at codons 41, 69, 70, 74, 184, and 215. At 1 to 3 months after change in therapy, patients without preexisting resistance mutations to the new drug (group S) had a significantly better evolution in viral load (reduction of 0.37 log(10)) compared with patients with known preexisting resistance mutation(s) (group R) (increase of 0.08 log(10)). This difference was particularly striking for patients with the baseline M184V mutation and whose treatment was modified by the addition of lamivudine. After 6 months the median difference in viral load evolution between the two groups increased to 0.61 log(10): the viral load of patients of group S was still 0.18 log(10) below baseline while patients of group R had an increase of 0.43 log(10) in viral load above baseline. Changes in CD4+ T cell counts were not significantly different. The evolution in viral load in HIV-1-infected patients with and without baseline resistance mutation(s) toward a newly added NRTI is significantly different at 1-3 months and at 6 months after changing or adding one NRTI.
authors.affiliation: Rega Institute and University Hospitals, Katholieke Universiteit Leuven, Belgium.
authors.forename: K
authors.initials: K
authors.lastname: Van Vaerenbergh
authors.forename: K
authors.initials: K
authors.lastname: Van Laethem
authors.forename: E
authors.initials: E
authors.lastname: Van Wijngaerden
authors.forename: J C
authors.initials: JC
authors.lastname: Schmit
authors.forename: F
authors.initials: F
authors.lastname: Schneider
authors.forename: L
authors.initials: L
authors.lastname: Ruiz
authors.forename: B
authors.initials: B
authors.lastname: Clotet
authors.forename: C
authors.initials: C
authors.lastname: Verhofstede
authors.forename: F
authors.initials: F
authors.lastname: Van Wanzeele
authors.forename: G
authors.initials: G
authors.lastname: Muyldermans
authors.forename: P
authors.initials: P
authors.lastname: Simons
authors.forename: L
authors.initials: L
authors.lastname: Stuyver
authors.forename: P
authors.initials: P
authors.lastname: Hermans
authors.forename: C
authors.initials: C
authors.lastname: Evans
authors.forename: E
authors.initials: E
authors.lastname: De Clercq
authors.forename: J
authors.initials: J
authors.lastname: Desmyter
authors.forename: A M
authors.initials: AM
authors.lastname: Vandamme
mesh_terms: D018791:CD4 Lymphocyte Count; D016049:Didanosine / Q000494:pharmacology / Q000627:therapeutic use; D004352:Drug Resistance, Microbial; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D009154:Mutation / Q000187:drug effects; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D012367:RNA, Viral / Q000032:analysis; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D019562:Viral Load; D016047:Zalcitabine / Q000494:pharmacology / Q000627:therapeutic use; D015215:Zidovudine / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D015215:Zidovudine; D016047:Zalcitabine; D016049:Didanosine