title: NRTI-sparing regimens yield higher rates of drug resistance than NRTI-based regimens for HIV-1 treatment.
abstract: To treat human immunodeficiency virus (HIV)-infected patients, international guidelines recommend the combination of two nucleos(t)ide reverse transcriptase inhibitors [N(t)RTIs] and a third agent [non-NRTI (NNRTI), boosted protease inhibitor (r/PI) or integrase inhibitor (INI)] for initial treatment. The objective of this study was to compare the selection of resistance to antiretrovirals (ARVs) for regimens containing or lacking N(t)RTIs in patients experiencing their first virological failure. Eligible patients had a first virological failure, defined as the occurrence of two consecutive HIV plasma viral loads ≥50copies/mL. Genotypic resistance testing was performed at the time of virological failure (on the second sample with detectable viral load ≥50copies/mL) in patients failing regimens of N(t)RTIs+r/PI or NNRTI or INI, r/PI+NNRTI or INI, and INI+NNRTI. Among 434 virological failures analysed, resistance testing results were available in 416 cases (95.9%). Higher rates of drug resistance were observed in patients receiving N(t)RTI-sparing regimens. When the combination of N(t)RTIs+r/PI was used, PIs protect themselves and the associated N(t)RTIs from the selection of resistance; however, this was not observed with the NNRTI+r/PI combination. The same phenomenon was observed for raltegravir: when used in combination with N(t)RTIs, INI resistance mutations were less frequently selected compared with its use in combination with PIs or NNRTIs. In conclusion, regimens of the ARV classes combined impact the frequency of resistance development. Lower resistance is observed for N(t)RTI-based regimens, with more therapeutic options for subsequent regimens after failure.
authors.affiliation: Université Pierre et Marie Curie - Paris 6, UMR S-943, 75013 Paris, France; INSERM, U943, 75013 Paris, France; AP-HP Groupe Hospitalier Pitié-Salpêtrière, Laboratoire de Virologie, 75013 Paris, France. Electronic address: anne-genevieve.marcelin@psl.aphp.fr.
authors.forename: A G
authors.initials: AG
authors.lastname: Marcelin
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, EA4409, 75018 Paris, France; AP-HP Groupe Hospitalier Bichat-Claude Bernard, HUPNVS, Laboratoire de Virologie, 75018 Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Visseaux
authors.affiliation: Université Pierre et Marie Curie - Paris 6, UMR S-943, 75013 Paris, France; INSERM, U943, 75013 Paris, France; AP-HP Groupe Hospitalier Pitié-Salpêtrière, Laboratoire de Virologie, 75013 Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Wirden
authors.affiliation: Université Pierre et Marie Curie - Paris 6, UMR S-943, 75013 Paris, France; INSERM, U943, 75013 Paris, France; AP-HP Groupe Hospitalier Saint-Antoine, Laboratoire de Virologie, 75011 Paris, France.
authors.forename: L
authors.initials: L
authors.lastname: Morand-Joubert
authors.affiliation: Université Pierre et Marie Curie - Paris 6, UMR S-943, 75013 Paris, France; INSERM, U943, 75013 Paris, France; AP-HP Groupe Hospitalier Pitié-Salpêtrière, Laboratoire de Virologie, 75013 Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Soulie
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, EA4409, 75018 Paris, France; AP-HP Groupe Hospitalier Bichat-Claude Bernard, HUPNVS, Laboratoire de Virologie, 75018 Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Charpentier
authors.affiliation: Université de Bordeaux, Microbiologie Fondamentale et Pathogénicité, UMR 5234, 33000 Bordeaux, France; CNRS, Microbiologie Fondamentale et Pathogénicité, UMR 5234, 33000 Bordeaux, France; Laboratoire de Virologie, CHU de Bordeaux, 33000 Bordeaux, France.
authors.forename: B
authors.initials: B
authors.lastname: Masquelier
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, EA4409, 75018 Paris, France; AP-HP Groupe Hospitalier Bichat-Claude Bernard, HUPNVS, Laboratoire de Virologie, 75018 Paris, France.
authors.forename: D
authors.initials: D
authors.lastname: Descamps
authors.affiliation: Université Pierre et Marie Curie - Paris 6, UMR S-943, 75013 Paris, France; INSERM, U943, 75013 Paris, France; AP-HP Groupe Hospitalier Pitié-Salpêtrière, Laboratoire de Virologie, 75013 Paris, France.
authors.forename: V
authors.initials: V
authors.lastname: Calvez
keywords: HIV-1; NRTI; Resistance