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J Antimicrob Chemother. 2008 Nov;62(5):914-20. doi: 10.1093/jac/dkn335. Epub 2008 Aug 20.

HIV-2 integrase gene polymorphism and phenotypic susceptibility of HIV-2 clinical isolates to the integrase inhibitors raltegravir and elvitegravir in vitro.

Collaborators (364)

Viard JP, Lortholary O, Boitard C, Maignan A, Meyohas MC, Girard PM, Bollens D, Meynard JL, Fonquernie L, Campa P, Boudraa C, Picard O, Cabanne B, Tangre P, Tredup J, Desplanque N, Brunet A, Guillevin L, Launay O, Compagnucci A, Boudjioudi M, Dubuisson JB, Finkielsztejn L, Guiard-Schmid JB, Pialloux G, Coridian A, Cardon B, Mariot P, Bani Sadr F, Nguyen T, Slama L, Vincensini JP, Jousselin V, Gilquin J, Cros A, Matheron S, Yéni P, Lepretre A, Mas S, Morau G, Landman R, Voyer C, Fournier I, Kissila A, Lariven S, Pahlavan G, Fegueux S, Klutse P, Longuet P, Tubiana R, Bricaire F, Zeller V, Pauchard M, Danis D, Meier F, Bloch M, Khuong MA, Méchali D, Labergere T, Taverne B, Khélil, Bentata M, Krivitzky A, Rouges F, Honore P, Teicher E, Vittecoq D, Timsit FJ, Morel P, Splinder E, Dos Santos S, Jeantils V, Tassi S, Semaille C, Patey O, Bantsimba J, Richier L, Quertainmont Y, Delfraissy JF, Rannou MT, Goujard C, Oksenhendler E, Gérard L, Martinie M, Cessot G, Beumont-Mauviel M, Simon-Poli AM, Vinceneux P, Lafon E, Zeng F, Froguel E, David-Ouaknine F, Lagarde P, Gourdel B, Welker Y, Chemlal K, Ruel M, Genet P, Sutton L, Lionnet F, Touhari T, Leprêtre A, Polomeni P, Zucman D, Bletry O, Majerholc C, Force G, Champetier de Ribes D, Coutellier A, Herson S, Amirate N, Brançon, Dupin N, Picketty C, Weiss L, Bengrait N, Karmochkine M, Derouineau D, Batisse D, Tisne-Dessus D, Garrait V, Chousterman M, Richier L, Masson Colin H, Hillion D, Cordonnier F, Blum L, Danne O, Eouzan M, Lesprit P, Sobel A, Lévy Y, Bourdillon F, Jung C, Dubreuil-Lemaire ML, Bideault H, Chardon P, Perrone V, Granier F, Leclerc V, Winter C, Janowski M, Bournerias F, Zini JM, Tobelem G, Lascoux-Combe C, Séréni D, Pintado C, Ponscarme D, Molina JM, Quertainmont Y, Colin de Verdière N, Lafaurie M, Brunet P, Schaeffer A, Godeau B, Chevojon P, Charpentier G, Petitdidier C, Kousignian P, Turpault I, Mourgeon B, Daum-Morelon S, Rouveix E, Dupond C, Berthe H, Kernbaum S, SteinMetzer R, Gachot B, Delassus JL, Malbec D, Bodard L, Gayraud M, Rafenne L, Meudec A, Israel-Biet D, Sors H, Imbert P, Debord T, Galanaud P, Emilie D, Boué F, Fior R, Bornarel D, Uludag A, Fantin B, Abgrall S, Bouchaud O, Thuyet Huynh Thi S, Compagnucci A, Huchon G, Pintado C, Asselah K, Bary M, Boulkhemair A, La Torre I, Beck C, Beck-Wirth G, Benomar M, Billau E, Barrier J, Raffi F, Hue H, Sicot M, Brosseau D, Stalder JF, Drobacheff C, Laurent R, Foltzer A, Lapine M, Cotte L, Trépo C, Benmakhlouf N, Brochier C, Thoirain V, Allègre T, Blanc AP, Drogoul MP, Gastaut JA, Le Moal S, Duhamel E, Hascouet A, Daniel-Sebbar S, Merrien D, Veyssier P, Granier P, Nau P, Choutet P, Besnier JM, Borsa Lebas F, Caron F, Debab Y, El Koubi S, Leclercq P, Brambilla C, Gailland MC, Adam G, Mornet M, Moreau J, Delmont JP, Brouqui P, Vandergheynst E, Tourba AM, Andrieux F, Cartier T, Bouvier C, Arvieux C, Poncelle C, Héry B, Delangle MH, Breux JP, Becq-Giraudon B, Arsac P, Lafeuillade A, Jolly P, Ragnaud JM, Durupt S, Chantereau MJ, Perré P, Suault I, Dutronc H, Dupon M, Raymond I, Mercié P, Pellegrin JL, Vialatte B, Simonet P, Montagne N, Bianco Y, Boyer L, May T, Wassoumbou S, Manoury B, Reynes J, Janbon F, Mansaray H, Tramoni C, Smail A, Schmit JL, Poinsignon Y, Jardel H, Le Pichon D, Jacomet C, Beytout J, Gourdon F, Buisson M, Portier H, Braconnier C, Fuzibet JG, Baclet V, Mouton Y, Dos Santos G, Pavel S, Marien MC, Riché A, Bonnefoy M, Bensalem M, Bru JP, Gaillat J, Rey D, Lang JM, Fischer P, Hess G, Abino JF, Foullon P, Rezzouk L, Gourbin P, Verdon R, Livrozet JM, Jeanblanc F, Le Moal G, Germain SC, Farbos S, Lucas F, Prevoteau du Clary F, Cochonnat K, Chennebault P, Liné D, Arnaud A, Randrianasolo N, Merle C, Lebrun C, Granet P, Caunègre L, Brun-Vézinet F, Damond F, Descamps D, Simon F, Palmer P, Morand-Joubert L, Cottalorda D, Schmitt MP, Billaudel P, Ferre V, Lab P, Bassignot A, Barin P, Boulanger P, Tardy D, Raoult D, Tamalet C, Avril P, Kerriguy M, Puel J, Jaafar A, Buffet-Janvresse P, Seigneurin P, Morand D, Agius P, Bourgoin M, Fleury P, Masquelier B, Duverlie D, Roussel M, La Feuille H, Henquell D, Chiacha A, Trevoux D, Delarbre D, Brehant C, Marty M, Watry P, Bocket D, Montes B.

Abstract

OBJECTIVES:

We investigated the in vitro phenotypic susceptibility of HIV-2 isolates from integrase inhibitor (INI)-naive patients to INIs and its relation to HIV-2 integrase gene polymorphism.

METHODS:

We determined the phenotypic susceptibility to raltegravir and elvitegravir of co-cultured isolates obtained from the HIV-2 ROD reference strain and from 14 clinical isolates. IC(50) values were compared with those for HIV-1 reference strains. HIV-2 integrase gene polymorphism was assessed in isolates from 52 INI-naive patients enrolled in the French HIV-2 cohort.

RESULTS:

Median raltegravir and elvitegravir IC(50) values for the 14 clinical HIV-2 isolates were 2.4 and 0.7 nM, respectively, and were similar to those observed for HIV-2 ROD and HIV-1 reference strains. Overall, 38% of HIV-2 integrase amino acids were polymorphic. The catalytic triad DDE and the HHCC and RKK motifs were fully conserved, at the same genomic positions as described in HIV-1. In subtype B isolates, the total length of the integrase gene varied, owing to the presence of stop codons at positions 288, 294, 297 and 302. Fourteen of the positions associated with substitutions conferring INI resistance in HIV-1 were polymorphic in HIV-2.

CONCLUSIONS:

Despite 40% heterogeneity between the HIV-1 and HIV-2 integrase genes, the phenotypic susceptibility of clinical HIV-2 isolates to INIs was similar to that of HIV-1. This new class of antiretroviral drugs thus represents a novel therapeutic possibility for HIV-2-infected patients who otherwise have few treatment options.

PMID:
18718922
[PubMed - indexed for MEDLINE]
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