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AIDS. 2008 Nov 12;22(17):2279-89. doi: 10.1097/QAD.0b013e328311d16f.

Viral resuppression and detection of drug resistance following interruption of a suppressive non-nucleoside reverse transcriptase inhibitor-based regimen.

Collaborators (746)

Lundgren JD, Jensen KB, Gey DC, Borup L, Pearson M, Jansson PO, Jensen BG, Tverland J, Juncker-Benzon H, Fox Z, Phillips AN, Darbyshire JH, Babiker AG, Palfreema AJ, Fleck SL, Dodd W, King E, Cordwell B, van Hooff F, Collaco-Moraes Y, Cooper DA, Emery S, Drummond FM, Connor SR, Satchell CS, Gunn S, Oka S, Delfino MA, Merlin K, McGinley C, Gordin F, Finley E, Dietz D, Chesson C, Vjecha M, Standridge B, Neaton JD, Bartsch G, DuChene A, George M, Grund B, Harrison E, Krun E, Larson G, Miller C, Nelson R, Neuhaus J, Roediger MP, Schultz T, Prineas R, Campbell C, Zhang ZM, Perez G, Lifson A, Duprez D, Hoy J, Lahart C, Perlman D, Price R, Prineas R, Rhame F, Sampson J, Worley J, Rein M, DerSimonian R, Brody BA, Daar ES, Dubler NN, Fleming TR, Freeman DJ, Kahn JP, Kim KM, Medoff G, Modlin JF, Moellering R Jr, Murray BE, Pick B, Robb ML, Scharfstein DO, Sugarman J, Tsiatis A, Tuazon C, Zoloth L, Klingman K, Lehrman S, Lazovski J, Belloso WH, Losso MH, Benetucci JA, Aquilia S, Bittar V, Bogdanowicz PE, Cahn PE, Casiró AD, Cassetti I, Contarelli JM, Corral JA, Crinejo A, Daciuk L, David DO, Guaragna G, Ishida MT, Krolewiecki A, Laplume HE, Lasala MB, Lourtau L, Lupo SH, Maranzana A, Masciottra F, Michaan M, Ruggieri L, Salazar E, Sánchez M, Somenzini C, Hoy JF, Rogers GD, Allworth AM, Anderson JS, Armishaw J, Barnes K, Carr A, Chiam A, Chuah JC, Curry MC, Dever RL, Donohue WA, Doong NC, Dwyer DE, Dyer J, Eu B, Ferguson VW, French MA, Garsia RJ, Gold J, Hudson JH, Jeganathan S, Konecny P, Leung J, McCormac CL, McMurchie M, Medland N, Moore RJ, Moussa MB, Orth D, Piper M, Read T, Roney JJ, Roth N, Shaw DR, Silvers J, Smith DJ, Street AC, Vale RJ, Wendt NA, Wood H, Youds DW, Zillman J, Rieger A, Tozeau V, Aichelburg A, Vetter N, Clumeck N, Dewit S, de Roo A, Kabeya K, Leonard P, Lynen L, Moutschen M, O'Doherty E, Pereira LC Jr, Souza TN, Schechter M, Zajdenverg R, Almeida MM, Araujo F, Bahia F, Brites C, Caseiro MM, Casseb J, Etzel A, Falco GG, Filho EC, Flint SR, Gonzales CR, Madruga JV, Passos RN, Reuter T, Sidi LC, Toscano AL, Zarowny D, Cherban E, Cohen J, Conway B, Dufour C, Ellis M, Foster A, Haase D, Haldane H, Houde M, Kato C, Klein M, Lessard B, Martel A, Martel C, McFarland N, Paradis E, Piche A, Sandre R, Schlech W, Schmidt S, Smaill F, Thompson B, Trottier S, Vezina S, Walmsley S, Wolff Reyes MJ, Northland R, Ostergaard L, Pedersen C, Nielsen H, Hergens L, Loftheim IR, Jensen KB, Raukas M, Zilmer K, Justinen J, Ristola M, Girard PM, Landman R, Abel S, Abgrall S, Amat K, Auperin L, Barruet R, Benalycherif A, Benammar N, Bensalem M, Bentata M, Besnier JM, Blanc M, Bouchaud O, Cabié A, Chavannet P, Chennebault JM, Dargere S, de la Tribonniere X, Debord T, Decaux N, Delgado J, Dupon M, Durant J, Frixon-Marin V, Genet C, Gérard L, Gilquin J, Hoen B, Jeantils V, Kouadio H, Leclercq P, Lelièvre JD, Levy Y, Michon CP, Nau P, Pacanowski J, Piketty C, Poizot-Martin I, Raymond I, Salmon D, Schmit JL, Serini MA, Simon A, Tassi S, Touam F, Verdon R, Weinbreck P, Weiss L, Yazdanpanah Y, Yeni P, Fätkenheuer G, Staszewski S, Bergmann F, Bitsch S, Bogner JR, Brockmeyer N, Esser S, Goebel FD, Hartmann M, Klinker H, Lehmann C, Lennemann T, Plettenberg A, Potthof A, Rockstroh J, Ross B, Stoehr A, Wasmuth JC, Wiedemeyer K, Winzer R, Hatzakis A, Touloumi G, Antoniadou A, Daikos GL, Dimitrakaki A, Gargalianos-Kakolyris P, Giannaris M, Karafoulidou A, Katsambas A, Katsarou O, Kontos AN, Kordossis T, Lazanas MK, Panagopoulos P, Panos G, Paparizos V, Papastamopoulos V, Petrikkos G, Sambatakou H, Skoutelis A, Tsogas N, Xylomenos G, Bergin CJ, Mooka B, Pollack S, Mamorksy MG, Agmon-Levin N, Karplus R, Kedem E, Maayan S, Shahar E, Sthoeger Z, Turner D, Yust I, Tambussi G, Rusconi V, Abeli C, Bechi M, Biglino A, Bonora S, Butini L, Carosi G, Casari S, Corpolongo A, De Gioanni M, Di Perri G, Di Pietro M, DOffizi G, Esposito R, Mazzotta F, Montroni M, Nardini G, Nozza S, Quirino T, Raise E, Honda M, Ishisaka M, Caplinskas S, Uzdaviniene V, Schmit JC, Staub T, Himmich H, Marhoum El Filali K, Mills GD, Blackmore T, Masters JA, Morgan J, Pithie A, Brunn J, Ormasssen V, La Rosa A, Guerra O, Espichan M, Gutierrez L, Mendo F, Salazar R, Knytz B, Horban A, Bakowska E, Beniowski M, Gasiorowski J, Kwiatkowski J, Antunes F, Castro RS, Doroana M, Horta A, Mansinho K, Miranda AC, Pinto IV, Valadas E, Vera J, Rakhmanova A, Vinogradova E, Yakovlev A, Zakharova N, Wood W, Orrel C, Gatell J, Arnaiz JA, Carrillo R, Clotet B, Dalmau D, González A, Jordano Q, Jou A, Knobel H, Larrousse M, Mata R, Moreno JS, Oretaga E, Pena JN, Pulido F, Rubio R, Sanz J, Viciana P, Hirschel B, Spycher R, Battegay M, Bernasconi E, Bottone S, Cavassini M, ChristeN A, Franc C, Furrer HJ, Gayet-Ageron A, Genné D, Hochstrasser S, Magenta L, Moens C, Müller N, Nüesch R, Phanuphak P, Ruxrungtham K, Pumpradit W, Chetchotisakd P, Dangthongdee S, Kiertiburanakul S, Klinbuayaem V, Mootsikapun P, Nonenoy S, Piyavong B, Prasithsirikul W, Raksakulkarn P, Gazzard BG, Ainsworth JG, Anderson J, Angus BJ, Barber TJ, Brook MG, Care CD, Chadwick DR, Chikohora M, Churchill DR, Cornforth D, Dockrell DH, Easterbrook PJ, Fox PA, Fox R, Gomez PA, Gompels MM, Harris GM, Herman S, Jackson AG, Jebakumar SP, Johnson MA, Kinghorn GR, Kuldanek KA, Larbalestie N, Leen C, Lumsden M, Maher T, Mantell J, Maw R, McKernan S, McLean L, Morris S, Muromba L, Orkin CM, Palfreeman AJ, Peters BS, Peto TE, Portsmouth SD, Rajamanoharan S, Ronan A, Schwenk A, Slinn MA, Stroud CJ, Thomas RC, Wansbrough-Jones MH, Whiles HJ, White DJ, Williams E, Williams IG, Youle M, Abrams DI, Acosta EA, Adams S, Adamski A, Andrews L, Antoniskis D, Aragon DR, Arduino R, Artz R, Bailowitz J, Barnett BJ, Baroni C, Barron M, Baxter JD, Beers D, Beilke M, Bemenderfer D, Bernard A, Besch CL, Bessesen MT, Bethel JT, Blue S, Blum JD, BoardenD S, Bolan RK, Borgman JB, Brar I, Braxton BK, Bredeek UF, Brennan R, Britt DE, Brockelman J, Brown S, Bruzzese V, Bulgin-Coleman D, Bullock DE, Cafaro V, Campbell B, Caras S, Carroll J, Casey KK, Chiang F, Childress G, Cindrich RB, Clark C, Climo M, Cohen C, Coley J, Condoluci DV, Contreras R, Corser D, Cozzolino J, Crane LR, Daley L, Dandridge D, D'Antuono V, Patron Darcourt Rizo JG, DeHovitz JA, DeJesus E, DesJardin J, Diaz-Linares M, Dietrich C, Dodson P, Dolce E, Elliott K, Erickson D, Estes M, Faber LL, Falbo J, Farrough MJ, Farthing CF, Ferrell-Gonzalez P, Flynn H, Frank C, Frank M, Freeman KF, French N, Friedland G, Fujita N, Gahagan L, Genther K, Gilson I, Goetz MB, Goodwin E, Graziano F, Guity CK, Gulick P, Gunderson ER, Hale CM, Hannah K, Henderson H, Hennessey K, Henry WK, Higgins DT, Hodder SL, Horowitz HW, Howe-Pittman M, Hubbard J, Hudson R, Hunter H, Hutelmyer C, Insignares MT, Jackson L, Jenny L, John M, Johnson DL, Johnson G, Johnson J, Kaatz J, Kaczmarski J, Kagan S, Kantor C, Kempner T, Kieckhaus K, Kimmel N, Klaus BM, Klimas N, Koeppe JR, Koirala J, Kopka J, Kostman JR, Kozal MJ, Kumar A, Labriola A, Lampiris H, Lamprecht C, Lattanzi KM, Lee J, Leggett J, Long C, Loquere A, Loveless K, Lucasti CJ, Luskin-Hawk R, MacVeigh M, Makohon LH, Mannheimer S, Markowitz NP, Marks C, Martinez N, Martorell C, McFeaters E, McGee B, McIntyre DM, McKee J, McManus E, Melecio LG, Melton D, Mercado S, Merrifield E, Mieras JA, Mogyoros M, Moran FM, Murphy K, Mushatt D, Mutic S, Nadeem I, Nahass R, Nixon D, O'Brien S, Ognjan A, O'Hearn M, O'Keefe K, Okhuysen PC, Oldfield E, Olson D, Orenstein R, Ortiz R, Osterberger J, Owen W, Parpart F, Pastore-Lange V, Paul S, Pavlatos A, Pearce DD, Pelz R, Perez G, Peterson S, Pierone G Jr, Pitrak D, Powers SL, Pujet HC, Raaum JW, Ravishankar J, Reeder J, Regevik N, Reilly NA, Reyelt C, Riddell J 4th, Rimland D, Robinson ML, Rodriguez AE, Rodriguez-Barradas MC, Rodriguez Derouen V, Roland R, Rosmarin C, Rossen WL, Rouff JR, Sampson JH, Sands M, Savini C, Schrader S, Schulte MM, Scott C, Scott R, Seedhom H, Sension M, Sheble-Hall A, Sheridan A, Shuter J, Slater LN, Slotten R, Slowinski D, Smith M, Snap S, Somboonwit C, States DM, Stewart M, Stringer G, Sullivan J, Summers KK, Swanson K, Sweeton IB, Szabo S, Tedaldi EM, Telzak EE, Temesgen Z, Thomas D, Thompson MA, Thompson S, Ting Hong Bong C, Tobin C, Uy J, Vaccaro A, Vasco LM, Vecino I, Verlinghieri GK, Visnegarwala F, Wade BH, Watson V, Weis SE, Weise JA, Weissman S, Wilkin AM, Williams L, Witter JH, Wojtusic L, Wright TJ, Yeh V, Young B, Zeana C, Zeh J, Savio E, Vacarezza M.

Abstract

BACKGROUND:

Interruption of a non-nucleoside reverse transcriptase inhibitor (NNRTI)-regimen is often necessary, but must be performed with caution because NNRTIs have a low genetic barrier to resistance. Limited data exist to guide clinical practice on the best interruption strategy to use.

METHODS:

Patients in the drug-conservation arm of the Strategies for Management of Antiretroviral Therapy (SMART) trial who interrupted a fully suppressive NNRTI-regimen were evaluated. From 2003, SMART recommended interruption of an NNRTI by a staggered interruption, in which the NNRTI was stopped before the NRTIs, or by replacing the NNRTI with another drug before interruption. Simultaneous interruption of all antiretrovirals was discouraged. Resuppression rates 4-8 months after reinitiating NNRTI-therapy were assessed, as was the detection of drug-resistance mutations within 2 months of the treatment interruption in a subset (N = 141).

RESULTS:

Overall, 601/688 (87.4%) patients who restarted an NNRTI achieved viral resuppression. The adjusted odds ratio (95% confidence interval) for achieving resuppression was 1.94 (1.02-3.69) for patients with a staggered interruption and 3.64 (1.37-9.64) for those with a switched interruption compared with patients with a simultaneous interruption. At least one NNRTI-mutation was detected in the virus of 16.4% patients with simultaneous interruption, 12.5% patients with staggered interruption and 4.2% patients with switched interruption. Fewer patients with detectable mutations (i.e. 69.2%) achieved HIV-RNA of 400 copies/ml or less compared with those in whom no mutations were detected (i.e. 86.7%; P = 0.05).

CONCLUSION:

In patients who interrupt a suppressive NNRTI-regimen, the choice of interruption strategy may influence resuppression rates when restarting a similar regimen. NNRTI drug-resistance mutations were observed in a relatively high proportion of patients. These data provide additional support for a staggered or switched interruption strategy for NNRTI drugs.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00027352.

PMID:
18981767
PMCID:
PMC2745911
DOI:
10.1097/QAD.0b013e328311d16f
[Indexed for MEDLINE]
Free PMC Article
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