Clinical benefit of dolutegravir in HIV-1 management related to the high genetic barrier to drug resistance

Virus Research

Volumn 239, Issue , 2017, Pages 1-9

  Brenner, Bluma G ^a   Wainberg, Mark A ^a  

^a MCGILL UNIVERSITY   (Canada)

Author keywords

Dolutegravir; Fitness; Inhibitors; Integrase; Replication; Resistance mutations

Indexed keywords

DOLUTEGRAVIR; INTEGRASE; VIRUS ENZYME; FUSED HETEROCYCLIC RINGS; INTEGRASE INHIBITOR;

ANTIRETROVIRAL THERAPY; ANTIVIRAL RESISTANCE; CLINICAL STUDY; COMBINATION DRUG THERAPY; DEVELOPING COUNTRY; DRUG EFFICACY; DRUG MONITORING; DRUG TOLERABILITY; ENZYME ACTIVITY; GENE MUTATION; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; MOLECULAR GENETICS; MONOTHERAPY; NONHUMAN; PRIORITY JOURNAL; REVIEW; VIRUS GENOME; VIRUS MUTATION; VIRUS REPLICATION; DRUG EFFECT; GENETICS; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; MICROBIAL SENSITIVITY TEST; MOLECULAR TYPING; MUTATION; VIROLOGY;

ANTIRETROVIRAL THERAPY, HIGHLY ACTIVE; DRUG RESISTANCE, VIRAL; HETEROCYCLIC COMPOUNDS, 3-RING; HIV INFECTIONS; HIV INTEGRASE INHIBITORS; HIV-1; HUMANS; MICROBIAL SENSITIVITY TESTS; MOLECULAR TYPING; MUTATION;

EID: 84997218216     PISSN: 01681702     EISSN: 18727492     Source Type: Journal    
DOI: 10.1016/j.virusres.2016.07.006     Document Type: Review

References (98)

1. Abram, M.E., Hluhanich, R.M., Goodman, D.D., Andreatta, K.N., Margot, N.A., Ye, L., Niedziela-Majka, A., Barnes, T.L., Novikov, N., Chen, X., Svarovskaia, E.S., McColl, D.J., White, K.L., Miller, M.D., Impact of primary elvitegravir resistance-associated mutations in HIV-1 integrase on drug susceptibility and viral replication fitness. Antimicrob. Agents Chemother. 57:6 (2013), 2654–2663.
2. Akil, B., Blick, G., Hagins, D.P., Ramgopal, M.N., Richmond, G.J., Samuel, R.M., Givens, N., Vavro, C., Song, I.H., Wynne, B., Ait-Khaled, M., team, V.-s., Dolutegravir versus placebo in subjects harbouring HIV-1 with integrase inhibitor resistance associated substitutions: 48-week results from VIKING-4, a randomized study. Antivir. Ther. 20:3 (2015), 343–348.
3. Armenia, D., Fabeni, L., Alteri, C., Di Pinto, D., Di Carlo, D., Bertoli, A., Gori, C., Carta, S., Fedele, V., Forbici, F., D'Arrigo, R., Svicher, V., Berno, G., Pizzi, D., Nicastri, E., Sarmati, L., Pinnetti, C., Ammassari, A., D'Offizi, G., Latini, A., Andreoni, M., Antinori, A., Ceccherini-Silberstein, F., Perno, C.F., Santoro, M.M., HIV-1 integrase genotyping is reliable and reproducible for routine clinical detection of integrase resistance mutations even in patients with low-level viraemia. J. Antimicrob. Chemother. 70:6 (2015), 1865–1873.
4. Bar-Magen, T., Sloan, R.D., Donahue, D.A., Kuhl, B.D., Zabeida, A., Xu, H., Oliveira, M., Hazuda, D.J., Wainberg, M.A., Identification of novel mutations responsible for resistance to MK-2048, a second-generation HIV-1 integrase inhibitor. J. Virol. 84:18 (2010), 9210–9216.
5. Baril, J.G., Angel, J.B., Gill, M.J., Gathe, J., Cahn, P., van Wyk, J., Walmsley, S., Dual therapy treatment strategies for the management of patients infected with HIV: a systematic review of current evidence in ARV-naive or ARV-experienced, virologically suppressed patients. PLoS One, 11(2), 2016, e0148231.
6. Brenner, B.G., Turner, D., Wainberg, M.A., HIV-1 drug resistance: can we overcome?. Expert Opin. Biol. Ther. 2:7 (2002), 751–761.
7. Brenner, B., Turner, D., Oliveira, M., Moisi, D., Detorio, M., Carobene, M., Marlink, R.G., Schapiro, J., Roger, M., Wainberg, M.A., A V106M mutation in HIV-1 clade C viruses exposed to efavirenz confers cross-resistance to non-nucleoside reverse transcriptase inhibitors. AIDS 17:1 (2003), F1–5.
8. Brenner, B.G., Oliveira, M., Doualla-Bell, F., Moisi, D.D., Ntemgwa, M., Frankel, F., Essex, M., Wainberg, M.A., HIV-1 subtype C viruses rapidly develop K65R resistance to tenofovir in cell culture. AIDS 20:9 (2006), F9–13.
9. Brenner, B.G., Roger, M., Moisi, D.D., Oliveira, M., Hardy, I., Turgel, R., Charest, H., Routy, J.P., Wainberg, M.A., Transmission networks of drug resistance acquired in primary/early stage HIV infection. AIDS 22:18 (2008), 2509–2515.
10. Brenner, B.G., Lowe, M., Moisi, D., Hardy, I., Gagnon, S., Charest, H., Baril, J.G., Wainberg, M.A., Roger, M., Subtype diversity associated with the development of HIV-1 resistance to integrase inhibitors. J. Med. Virol., 2011.
11. Brenner, B.G., Lowe, M., Moisi, D., Hardy, I., Gagnon, S., Charest, H., Baril, J.G., Wainberg, M.A., Roger, M., Subtype diversity associated with the development of HIV-1 resistance to integrase inhibitors. J. Med. Virol. 83:5 (2011), 751–759.
12. Brenner, B.G., Thomas, R., Blanco, J.L., Ibanescu, R.I., Oliveira, M., Mesplede, T., Golubkov, O., Roger, M., Garcia, F., Martinez, E., Wainberg, M.A., Development of a G118R mutation in HIV-1 integrase following a switch to dolutegravir monotherapy leading to cross-resistance to integrase inhibitors. J. Antimicrob. Chemother., 2016.
13. Cahn, P., Pozniak, A.L., Mingrone, H., Shuldyakov, A., Brites, C., Andrade-Villanueva, J.F., Richmond, G., Buendia, C.B., Fourie, J., Ramgopal, M., Hagins, D., Felizarta, F., Madruga, J., Reuter, T., Newman, T., Small, C.B., Lombaard, J., Grinsztejn, B., Dorey, D., Underwood, M., Griffith, S., Min, S., extended, S.S.T., Dolutegravir versus raltegravir in antiretroviral-experienced, integrase-inhibitor-naive adults with HIV: week 48 results from the randomised, double-blind, non-inferiority SAILING study. Lancet 382:9893 (2013), 700–708.
14. Canducci, F., Ceresola, E.R., Boeri, E., Spagnuolo, V., Cossarini, F., Castagna, A., Lazzarin, A., Clementi, M., Cross-resistance profile of the novel integrase inhibitor Dolutegravir (S/GSK1349572) using clonal viral variants selected in patients failing raltegravir. J. Infect. Dis. 204:11 (2011), 1811–1815.
15. Canducci, F., Ceresola, E.R., Saita, D., Castagna, A., Gianotti, N., Underwood, M., Burioni, R., Lazzarin, A., Clementi, M., In vitro phenotypes to elvitegravir and dolutegravir in primary macrophages and lymphocytes of clonal recombinant viral variants selected in patients failing raltegravir. J. Antimicrob. Chemother. 68:11 (2013), 2525–2532.
16. Castagna, A., Maggiolo, F., Penco, G., Wright, D., Mills, A., Grossberg, R., Molina, J.M., Chas, J., Durant, J., Moreno, S., Doroana, M., Ait-Khaled, M., Huang, J., Min, S., Song, I., Vavro, C., Nichols, G., Yeo, J.M., Group, V.-S., Dolutegravir in antiretroviral-experienced patients with raltegravir- and/or elvitegravir-resistant HIV-1: 24-week results of the phase III VIKING-3 study. J. Infect. Dis. 210:3 (2014), 354–362.
17. Ceccherini-Silberstein, F., Van Baelen, K., Armenia, D., Trignetti, M., Rondelez, E., Fabeni, L., Scopelliti, F., Pollicita, M., Van Wesenbeeck, L., Van Eygen, V., Dori, L., Sarmati, L., Aquaro, S., Palamara, G., Andreoni, M., Stuyver, L.J., Perno, C.F., Secondary integrase resistance mutations found in HIV-1 minority quasispecies in integrase therapy-naive patients have little or no effect on susceptibility to integrase inhibitors. Antimicrob. Agents Chemother. 54:9 (2010), 3938–3948.
18. Charest, H., Doualla-Bell, F., Cantin, R., Murphy, D.G., Lemieux, L., Brenner, B., Hardy, I., Moisi, D., Lo, E., Baril, J.G., Wainberg, M.A., Roger, M., Tremblay, C., A significant reduction in the frequency of HIV-1 drug resistance in quebec from 2001 to 2011 is associated with a decrease in the monitored viral load. PLoS One, 9(10), 2014, e109420.
19. Clotet, B., Feinberg, J., van Lunzen, J., Khuong-Josses, M.A., Antinori, A., Dumitru, I., Pokrovskiy, V., Fehr, J., Ortiz, R., Saag, M., Harris, J., Brennan, C., Fujiwara, T., Min, S., Team, I.N.G.S., Once-daily dolutegravir versus darunavir plus ritonavir in antiretroviral-naive adults with HIV-1 infection (FLAMINGO): 48 week results from the randomised open-label phase 3b study. Lancet 383:9936 (2014), 2222–2231.
20. Cohen, M.S., Chen, Y.Q., McCauley, M., Gamble, T., Hosseinipour, M.C., Kumarasamy, N., Hakim, J.G., Kumwenda, J., Grinsztejn, B., Pilotto, J.H., Godbole, S.V., Mehendale, S., Chariyalertsak, S., Santos, B.R., Mayer, K.H., Hoffman, I.F., Eshleman, S.H., Piwowar-Manning, E., Wang, L., Makhema, J., Mills, L.A., de Bruyn, G., Sanne, I., Eron, J., Gallant, J., Havlir, D., Swindells, S., Ribaudo, H., Elharrar, V., Burns, D., Taha, T.E., Nielsen-Saines, K., Celentano, D., Essex, M., Fleming, T.R., Prevention of HIV-1 infection with early antiretroviral therapy. N. Engl. J. Med. 365:6 (2011), 493–505.
21. Cohn, J., Bekker, L.G., Bygrave, H., Calmy, A., Hit me with your best shot: dolutegravir—a space in the next WHO guidelines?. AIDS 29:16 (2015), 2067–2070.
22. Collier, A.C., Chun, T.W., Maenza, J., Coombs, R.W., Tapia, K., Chang, M., Stevens, C.E., Justement, J.S., Murray, D., Stekler, J.D., Mullins, J.I., Holte, S.E., A pilot study of raltegravir plus combination antiretroviral therapy in early human immunodeficiency virus infection: challenges and lessons learned. Biores. Open Access 5:1 (2016), 15–21.
23. DeJesus, E., Rockstroh, J.K., Henry, K., Molina, J.M., Gathe, J., Ramanathan, S., Wei, X., Yale, K., Szwarcberg, J., White, K., Cheng, A.K., Kearney, B.P., Team, G.S.S., Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate versus ritonavir-boosted atazanavir plus co-formulated emtricitabine and tenofovir disoproxil fumarate for initial treatment of HIV-1 infection: a randomised, double-blind, phase 3, non-inferiority trial. Lancet 379:9835 (2012), 2429–2438.
24. DeJesus, E., Rockstroh, J.K., Lennox, J.L., Saag, M.S., Lazzarin, A., Zhao, J., Wan, H., Rodgers, A.J., Walker, M.L., Miller, M., DiNubile, M.J., Nguyen, B.Y., Teppler, H., Leavitt, R., Sklar, P., Investigators, S., Efficacy of raltegravir versus efavirenz when combined with tenofovir/emtricitabine in treatment-naive HIV-1-infected patients: week-192 overall and subgroup analyses from STARTMRK. HIV Clin. Trials 13:4 (2012), 228–232.
25. Descamps, D., Peytavin, G., Visseaux, B., Tubiana, R., Damond, F., Campa, P., Charpentier, C., Khuong-Josses, M.A., Duvivier, C., Karmochkine, M., Lukiana, T., Matheron, S., Dolutegravir in HIV-2-infected patients with resistant virus to first-line integrase inhibitors from the French named patient program. Clin. Infect. Dis. 60:10 (2015), 1521–1527.
26. Donnell, D.J., Hall, H.I., Gamble, T., Beauchamp, G., Griffin, A.B., Torian, L.V., Branson, B., El-Sadr, W.M., Use of HIV case surveillance system to design and evaluate site-randomized interventions in an HIV prevention study: HPTN 065. Open AIDS J. 6 (2012), 122–130.
27. Dooley, K.E., Sayre, P., Borland, J., Purdy, E., Chen, S., Song, I., Peppercorn, A., Everts, S., Piscitelli, S., Flexner, C., Safety, tolerability, and pharmacokinetics of the HIV integrase inhibitor dolutegravir given twice daily with rifampin or once daily with rifabutin: results of a phase 1 study among healthy subjects. J. Acquir. Immune Defic. Syndr. 62:1 (2013), 21–27.
28. Doyle, T., Dunn, D.T., Ceccherini-Silberstein, F., De Mendoza, C., Garcia, F., Smit, E., Fearnhill, E., Marcelin, A.G., Martinez-Picado, J., Kaiser, R., Geretti, A.M., Group, C.S., Integrase inhibitor (INI) genotypic resistance in treatment-naive and raltegravir-experienced patients infected with diverse HIV-1 clades. J. Antimicrob. Chemother. 70:11 (2015), 3080–3086.
29. Eron, J.J., Clotet, B., Durant, J., Katlama, C., Kumar, P., Lazzarin, A., Poizot-Martin, I., Richmond, G., Soriano, V., Ait-Khaled, M., Fujiwara, T., Huang, J., Min, S., Vavro, C., Yeo, J., Group, V.S., Safety and efficacy of dolutegravir in treatment-experienced subjects with raltegravir-resistant HIV type 1 infection: 24-week results of the VIKING Study. J. Infect. Dis. 207:5 (2013), 740–748.
30. Fernandez-Caballero, J.A., Chueca, N., Alvarez, M., Gonzalez, D., Garcia, F., Use of deep sequencing data for routine analysis of HIV resistance in newly diagnosed patients. J. Int. AIDS Soc., 17(4 Sulppl. 3), 2014, 19748.
31. Fernandez-Caballero, J.A., Chueca, N., Alvarez, M., Merida, M.D., Lopez, J., Sanchez, J.A., Vinuesa, D., Martinez, M.A., Hernandez, J., Garcia, F., Usefulness of Integrase resistance testing in proviral HIV-1 DNA in patients with Raltegravir prior failure. BMC Infect. Dis., 16(1), 2016, 197.
32. Figueroa, M.I.S.O., Patterson, P., Gun, A., Rolon, M., Cahn, P., Dolutegravir-lamivudine as initial therapy in HIV-infected. ARTnaive Patients: First Results of the PADDLE Trial. 15th European AIDS Conference, 2015.
33. Fonager, J., Larsson, J.T., Hussing, C., Engsig, F.N., Nielsen, C., Fischer, T.K., Identification of minority resistance mutations in the HIV-1 integrase coding region using next generation sequencing. J. Clin. Virol. 73 (2015), 95–100.
34. Garcia-Diaz, A., McCormick, A., Booth, C., Gonzalez, D., Sayada, C., Haque, T., Johnson, M., Webster, D., Analysis of transmitted HIV-1 drug resistance using 454 ultra-deep-sequencing and the DeepChek((R))-HIV system. J. Int. AIDS Soc., 17(4 Suppl. 3), 2014, 19752.
35. Grant, R.M., Lama, J.R., Anderson, P.L., McMahan, V., Liu, A.Y., Vargas, L., Goicochea, P., Casapia, M., Guanira-Carranza, J.V., Ramirez-Cardich, M.E., Montoya-Herrera, O., Fernandez, T., Veloso, V.G., Buchbinder, S.P., Chariyalertsak, S., Schechter, M., Bekker, L.G., Mayer, K.H., Kallas, E.G., Amico, K.R., Mulligan, K., Bushman, L.R., Hance, R.J., Ganoza, C., Defechereux, P., Postle, B., Wang, F., McConnell, J.J., Zheng, J.H., Lee, J., Rooney, J.F., Jaffe, H.S., Martinez, A.I., Burns, D.N., Glidden, D.V., Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N. Engl. J. Med. 363:27 (2010), 2587–2599.
36. Grinsztejn, B., Hosseinipour, M.C., Ribaudo, H.J., Swindells, S., Eron, J., Chen, Y.Q., Wang, L., Ou, S.S., Anderson, M., McCauley, M., Gamble, T., Kumarasamy, N., Hakim, J.G., Kumwenda, J., Pilotto, J.H., Godbole, S.V., Chariyalertsak, S., de Melo, M.G., Mayer, K.H., Eshleman, S.H., Piwowar-Manning, E., Makhema, J., Mills, L.A., Panchia, R., Sanne, I., Gallant, J., Hoffman, I., Taha, T.E., Nielsen-Saines, K., Celentano, D., Essex, M., Havlir, D., Cohen, M.S., Team, H.A.S., Effects of early versus delayed initiation of antiretroviral treatment on clinical outcomes of HIV-1 infection: results from the phase 3 HPTN 052 randomised controlled trial. Lancet Infect. Dis. 14:4 (2014), 281–290.
37. Group, I.S.S., Lundgren, J.D., Babiker, A.G., Gordin, F., Emery, S., Grund, B., Sharma, S., Avihingsanon, A., Cooper, D.A., Fatkenheuer, G., Llibre, J.M., Molina, J.M., Munderi, P., Schechter, M., Wood, R., Klingman, K.L., Collins, S., Lane, H.C., Phillips, A.N., Neaton, J.D., Initiation of antiretroviral therapy in early asymptomatic HIV infection. N. Engl. J. Med. 373:9 (2015), 795–807.
38. Gubavu, C., Prazuck, T., Niang, M., Buret, J., Mille, C., Guinard, J., Avettand-Fenoel, V., Hocqueloux, L., Dolutegravir-based monotherapy or dual therapy maintains a high proportion of viral suppression even in highly experienced HIV-1-infected patients. J. Antimicrob. Chemother. 71:4 (2016), 1046–1050.
39. Hamers, R.L., Wallis, C.L., Kityo, C., Siwale, M., Mandaliya, K., Conradie, F., Botes, M.E., Wellington, M., Osibogun, A., Sigaloff, K.C., Nankya, I., Schuurman, R., Wit, F.W., Stevens, W.S., van Vugt, M., de Wit, T.F., HIV-1 drug resistance in antiretroviral-naive individuals in sub-Saharan Africa after rollout of antiretroviral therapy: a multicentre observational study. Lancet Infect. Dis. 11:10 (2011), 750–759.
40. Hardy, I., Brenner, B., Quashie, P., Thomas, R., Petropoulos, C., Huang, W., Moisi, D., Wainberg, M.A., Roger, M., Evolution of a novel pathway leading to dolutegravir resistance in a patient harbouring N155H and multiclass drug resistance. J. Antimicrob. Chemother. 70:2 (2015), 405–411.
41. Hofstra, L.M., Sauvageot, N., Albert, J., Alexiev, I., Garcia, F., Struck, D., Van de Vijver, D.A., Asjo, B., Beshkov, D., Coughlan, S., Descamps, D., Griskevicius, A., Hamouda, O., Horban, A., Van Kasteren, M., Kolupajeva, T., Kostrikis, L.G., Liitsola, K., Linka, M., Mor, O., Nielsen, C., Otelea, D., Paraskevis, D., Paredes, R., Poljak, M., Puchhammer-Stockl, E., Sonnerborg, A., Stanekova, D., Stanojevic, M., Van Laethem, K., Zazzi, M., Zidovec Lepej, S., Boucher, C.A., Schmit, J.C., Wensing, A.M., Program, S., Transmission of HIV drug resistance and the predicted effect on current first-line regimens in europe. Clin. Infect. Dis. 62:5 (2016), 655–663.
42. Johnson, M., Borland, J., Chen, S., Savina, P., Wynne, B., Piscitelli, S., Effects of boceprevir and telaprevir on the pharmacokinetics of dolutegravir. Br. J. Clin. Pharmacol. 78:5 (2014), 1043–1049.
43. Jones, A., Cremin, I., Abdullah, F., Idoko, J., Cherutich, P., Kilonzo, N., Rees, H., Hallett, T., O'Reilly, K., Koechlin, F., Schwartlander, B., de Zalduondo, B., Kim, S., Jay, J., Huh, J., Piot, P., Dybul, M., Transformation of HIV from pandemic to low-endemic levels: a public health approach to combination prevention. Lancet 384:9939 (2014), 272–279.
44. Katlama, C.S.C., Blanc, C., Denis, A., Caby, F., Schneider, L., et al. Dolutegravir monotherapy in patients with suppressed HIV viremia. 15th European AIDS Conference., 2015.
45. Kobayashi, M., Yoshinaga, T., Seki, T., Wakasa-Morimoto, C., Brown, K.W., Ferris, R., Foster, S.A., Hazen, R.J., Miki, S., Suyama-Kagitani, A., Kawauchi-Miki, S., Taishi, T., Kawasuji, T., Johns, B.A., Underwood, M.R., Garvey, E.P., Sato, A., Fujiwara, T., In vitro antiretroviral properties of S/GSK1349572, a next-generation HIV integrase inhibitor. Antimicrob. Agents Chemother. 55:2 (2011), 813–821.
46. Lennox, J.L., Landovitz, R.J., Ribaudo, H.J., Ofotokun, I., Na, L.H., Godfrey, C., Kuritzkes, D.R., Sagar, M., Brown, T.T., Cohn, S.E., McComsey, G.A., Aweeka, F., Fichtenbaum, C.J., Presti, R.M., Koletar, S.L., Haas, D.W., Patterson, K.B., Benson, C.A., Baugh, B.P., Leavitt, R.Y., Rooney, J.F., Seekins, D., Currier, J.S., Team, A.A., Efficacy and tolerability of 3 nonnucleoside reverse transcriptase inhibitor-sparing antiretroviral regimens for treatment-naive volunteers infected with HIV-1: a randomized, controlled equivalence trial. Ann. Intern. Med. 161:7 (2014), 461–471.
47. Llibre, J.M., Walmsley, S., Gatell, J.M., Backbones versus core agents in initial ART regimens: one game, two players. J. Antimicrob. Chemother. 71:4 (2016), 856–861.
48. Llibre, J.M., First-line boosted protease inhibitor-based regimens in treatment-naive HIV-1-infected patients—making a good thing better. AIDS Rev. 11:4 (2009), 215–222.
49. Low, A.J., Swenson, L.C., Harrigan, P.R., HIV coreceptor phenotyping in the clinical setting. AIDS Rev. 10:3 (2008), 143–151.
50. Malet, I., Delelis, O., Valantin, M.A., Montes, B., Soulie, C., Wirden, M., Tchertanov, L., Peytavin, G., Reynes, J., Mouscadet, J.F., Katlama, C., Calvez, V., Marcelin, A.G., Mutations associated with failure of raltegravir treatment affect integrase sensitivity to the inhibitor in vitro. Antimicrob. Agents Chemother. 52:4 (2008), 1351–1358.
51. Malet, I., Fourati, S., Charpentier, C., Morand-Joubert, L., Armenia, D., Wirden, M., Sayon, S., Van Houtte, M., Ceccherini-Silberstein, F., Brun-Vezinet, F., Perno, C.F., Descamps, D., Capt, A., Calvez, V., Marcelin, A.G., The HIV-1 integrase G118R mutation confers raltegravir resistance to the CRF02_AG HIV-1 subtype. J. Antimicrob. Chemother. 66:12 (2011), 2827–2830.
52. Manasa, J., Danaviah, S., Lessells, R., Elshareef, M., Tanser, F., Wilkinson, E., Pillay, S., Mthiyane, H., Mwambi, H., Pillay, D., Oliveira, T., Increasing HIV-1 drug resistance between 2010 and 2012 in adults participating in population-based HIV surveillance in rural KwaZulu-Natal, South Africa. AIDS Res. Hum. Retroviruses, 2016.
53. Marconi, V.C., Sunpath, H., Lu, Z., Gordon, M., Koranteng-Apeagyei, K., Hampton, J., Carpenter, S., Giddy, J., Ross, D., Holst, H., Losina, E., Walker, B.D., Kuritzkes, D.R., Prevalence of HIV-1 drug resistance after failure of a first highly active antiretroviral therapy regimen in KwaZulu Natal. S. Afr. Clin. Infect. Dis. 46:10 (2008), 1589–1597.
54. Masso, M., Sequence-based predictive models of resistance to HIV-1 integrase inhibitors: an n-grams approach to phenotype assessment. Curr. HIV Res. 13:6 (2015), 497–502.
55. McCallum, M., Oliveira, M., Ibanescu, R.I., Kramer, V.G., Moisi, D., Asahchop, E.L., Brenner, B.G., Harrigan, P.R., Xu, H., Wainberg, M.A., Basis for early and preferential selection of the E138K mutation in HIV-1 reverse transcriptase. Antimicrob. Agents Chemother. 57:10 (2013), 4681–4688.
56. McCormack, S., Dunn, D.T., Desai, M., Dolling, D.I., Gafos, M., Gilson, R., Sullivan, A.K., Clarke, A., Reeves, I., Schembri, G., Mackie, N., Bowman, C., Lacey, C.J., Apea, V., Brady, M., Fox, J., Taylor, S., Antonucci, S., Khoo, S.H., Rooney, J., Nardone, A., Fisher, M., McOwan, A., Phillips, A.N., Johnson, A.M., Gazzard, B., Gill, O.N., Pre-exposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD): effectiveness results from the pilot phase of a pragmatic open-label randomised trial. Lancet, 2015.
57. Mesplede, T., Quashie, P.K., Osman, N., Han, Y., Singhroy, D.N., Lie, Y., Petropoulos, C.J., Huang, W., Wainberg, M.A., Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. Retrovirology, 10, 2013, 22.
58. Mesplede, T., Quashie, P.K., Zanichelli, V., Wainberg, M.A., Integrase strand transfer inhibitors in the management of HIV-positive individuals. Ann. Med. 46:3 (2014), 123–129.
59. Mesplede, T., Moisi, D., Oliveira, M., Ibanescu, I., Ohnona, F., Brenner, B., Wainberg, M.A., Dolutegravir inhibits HIV-1 Env evolution in primary human cells. AIDS 29:6 (2015), 659–665.
60. Miller, M.M., Liedtke, M.D., Lockhart, S.M., Rathbun, R.C., The role of dolutegravir in the management of HIV infection. Infect. Drug Resist. 8 (2015), 19–29.
61. Molina, J.M., Lamarca, A., Andrade-Villanueva, J., Clotet, B., Clumeck, N., Liu, Y.P., Zhong, L., Margot, N., Cheng, A.K., Chuck, S.L., Study, T., Efficacy and safety of once daily elvitegravir versus twice daily raltegravir in treatment-experienced patients with HIV-1 receiving a ritonavir-boosted protease inhibitor: randomised, double-blind, phase 3, non-inferiority study. Lancet Infect. Dis. 12:1 (2012), 27–35.
62. Montaner, J.S., Lima, V.D., Barrios, R., Yip, B., Wood, E., Kerr, T., Shannon, K., Harrigan, P.R., Hogg, R.S., Daly, P., Kendall, P., Association of highly active antiretroviral therapy coverage, population viral load, and yearly new HIV diagnoses in British Columbia, Canada: a population-based study. Lancet 376:9740 (2010), 532–539.
63. Moreira, J., Dolutegravir monotherapy as a simplified strategy in virologically suppressed HIV-1-infected patients. J. Antimicrob. Chemother., 2016.
64. Munir, S., Thierry, E., Malet, I., Subra, F., Calvez, V., Marcelin, A.G., Deprez, E., Delelis, O., G118R and F121Y mutations identified in patients failing raltegravir treatment confer dolutegravir resistance. J. Antimicrob. Chemother. 70:3 (2015), 739–749.
65. Novitsky, V., Zahralban-Steele, M., McLane, M.F., Moyo, S., van Widenfelt, E., Gaseitsiwe, S., Makhema, J., Essex, M., Long-range HIV genotyping using viral RNA and proviral DNA for analysis of HIV drug resistance and HIV clustering. J. Clin. Microbiol. 53:8 (2015), 2581–2592.
66. Oliveira, M., Brenner, B.G., Wainberg, M.A., Isolation of drug-resistant mutant HIV variants using tissue culture drug selection. Methods Mol. Biol. 485 (2009), 427–433.
67. Oliveira, M., Mesplede, T., Quashie, P.K., Moisi, D., Wainberg, M.A., Resistance mutations against dolutegravir in HIV integrase impair the emergence of resistance against reverse transcriptase inhibitors. AIDS 28:6 (2014), 813–819.
68. Oliveira, M., Mesplede, T., Moisi, D., Ibanescu, R.I., Brenner, B., Wainberg, M.A., The dolutegravir R263K resistance mutation in HIV-1 integrase is incompatible with the emergence of resistance against raltegravir. AIDS, 2015.
69. Osterholzer, D.A., Goldman, M., Dolutegravir: a next-generation integrase inhibitor for treatment of HIV infection. Clin. Infect. Dis. 59:2 (2014), 265–271.
70. Parkin, N., Chappey, C., Maroldo, L., Bates, M., Hellmann, N.S., Petropoulos, C.J., Phenotypic and genotypic HIV-1 drug resistance assays provide complementary information. J. Acquir. Immune Defic. Syndr. 31:2 (2002), 128–136.
71. Pattery, T., Verlinden, Y., De Wolf, H., Nauwelaers, D., Van Baelen, K., Van Houtte, M., Mc Kenna, P., Villacian, J., Development and performance of conventional HIV-1 phenotyping (Antivirogram(R)) and genotype-based calculated phenotyping assay (virco(R)TYPE HIV-1) on protease and reverse transcriptase genes to evaluate drug resistance. Intervirology 55:2 (2012), 138–146.
72. Pinnetti, C., Tintoni, M., Ammassari, A., Tamburrini, E., Bernardi, S., Liuzzi, G., Scambia, G., Perno, C.F., Floridia, M., Antinori, A., Cavaliere, A.F., Successful prevention of HIV mother-to-child transmission with dolutegravir-based combination antiretroviral therapy in a vertically infected pregnant woman with multiclass highly drug-resistant HIV-1. AIDS 29:18 (2015), 2534–2537.
73. Plaza-Diaz, J., Fernandez-Caballero, J.A., Chueca, N., Garcia, F., Gomez-Llorente, C., Saez-Lara, M.J., Fontana, L., Gil, A., Pyrosequencing analysis reveals changes in intestinal microbiota of healthy adults who received a daily dose of immunomodulatory probiotic strains. Nutrients 7:6 (2015), 3999–4015.
74. Quashie, P.K., Mesplede, T., Han, Y.S., Oliveira, M., Singhroy, D.N., Fujiwara, T., Underwood, M.R., Wainberg, M.A., Characterization of the R263K mutation in HIV-1 integrase that confers low-level resistance to the second-generation integrase strand transfer inhibitor dolutegravir. J. Virol. 86:5 (2012), 2696–2705.
75. Quashie, P.K., Oliviera, M., Veres, T., Osman, N., Han, Y.S., Hassounah, S., Lie, Y., Huang, W., Mesplede, T., Wainberg, M.A., Differential effects of the G118R, H51Y, and E138K resistance substitutions in different subtypes of HIV integrase. J. Virol. 89:6 (2015), 3163–3175.
76. Raffi, F., Jaeger, H., Quiros-Roldan, E., Albrecht, H., Belonosova, E., Gatell, J.M., Baril, J.G., Domingo, P., Brennan, C., Almond, S., Min, S., extended, S.-S.G., Once-daily dolutegravir versus twice-daily raltegravir in antiretroviral-naive adults with HIV-1 infection (SPRING-2 study): 96 week results from a randomised, double-blind, non-inferiority trial. Lancet Infect. Dis. 13:11 (2013), 927–935.
77. Raffi, F., Pozniak, A.L., Wainberg, M.A., Has the time come to abandon efavirenz for first-line antiretroviral therapy?. J. Antimicrob. Chemother. 69:7 (2014), 1742–1747.
78. Raffi, F., Rachlis, A., Brinson, C., Arasteh, K., Gorgolas, M., Brennan, C., Pappa, K., Almond, S., Granier, C., Nichols, W.G., Cuffe, R.L., Eron, J. Jr., Walmsley, S., Dolutegravir efficacy at 48 weeks in key subgroups of treatment-naive HIV-infected individuals in three randomized trials. AIDS 29:2 (2015), 167–174.
79. Rhee, S.Y., Blanco, J.L., Jordan, M.R., Taylor, J., Lemey, P., Varghese, V., Hamers, R.L., Bertagnolio, S., Rinke de Wit, T.F., Aghokeng, A.F., Albert, J., Avi, R., Avila-Rios, S., Bessong, P.O., Brooks, J.I., Boucher, C.A., Brumme, Z.L., Busch, M.P., Bussmann, H., Chaix, M.L., Chin, B.S., D'Aquin, T.T., De Gascun, C.F., Derache, A., Descamps, D., Deshpande, A.K., Djoko, C.F., Eshleman, S.H., Fleury, H., Frange, P., Fujisaki, S., Harrigan, P.R., Hattori, J., Holguin, A., Hunt, G.M., Ichimura, H., Kaleebu, P., Katzenstein, D., Kiertiburanakul, S., Kim, J.H., Kim, S.S., Li, Y., Lutsar, I., Morris, L., Ndembi, N., Ng, K.P., Paranjape, R.S., Peeters, M., Poljak, M., Price, M.A., Ragonnet-Cronin, M.L., Reyes-Teran, G., Rolland, M., Sirivichayakul, S., Smith, D.M., Soares, M.A., Soriano, V.V., Ssemwanga, D., Stanojevic, M., Stefani, M.A., Sugiura, W., Sungkanuparph, S., Tanuri, A., Tee, K.K., Truong, H.H., van de Vijver, D.A., Vidal, N., Yang, C., Yang, R., Yebra, G., Ioannidis, J.P., Vandamme, A.M., Shafer, R.W., Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance: an individual-patient- and sequence-level meta-analysis. PLoS Med., 12(4), 2015, e1001810.
80. Rhee, S.Y., Jordan, M.R., Raizes, E., Chua, A., Parkin, N., Kantor, R., Van Zyl, G.U., Mukui, I., Hosseinipour, M.C., Frenkel, L.M., Ndembi, N., Hamers, R.L., Rinke de Wit, T.F., Wallis, C.L., Gupta, R.K., Fokam, J., Zeh, C., Schapiro, J.M., Carmona, S., Katzenstein, D., Tang, M., Aghokeng, A.F., De Oliveira, T., Wensing, A.M., Gallant, J.E., Wainberg, M.A., Richman, D.D., Fitzgibbon, J.E., Schito, M., Bertagnolio, S., Yang, C., Shafer, R.W., HIV-1 drug resistance mutations: potential applications for point-of-care genotypic resistance testing. PLoS One, 10(12), 2015, e0145772.
81. Rhee, S.Y., Sankaran, K., Varghese, V., Winters, M., Hurt, C.B., Eron, J.J., Parkin, N., Holmes, S.P., Holodniy, M., Shafer, R.W., HIV-1 protease, reverse transcriptase, and integrase variation. J. Virol., 2016.
82. Rojas, J., Blanco, J.L., Marcos, M.A., Lonca, M., Tricas, A., Moreno, L., Gonzalez-Cordon, A., Torres, B., Mallolas, J., Garcia, F., Gatell, J.M., Martinez, E., Dolutegravir monotherapy in HIV-infected patients with sustained viral suppression. J. Antimicrob. Chemother., 2016.
83. Salou, M., Dagnra, A.Y., Butel, C., Vidal, N., Serrano, L., Takassi, E., Konou, A.A., Houndenou, S., Dapam, N., Singo-Tokofai, A., Pitche, P., Atakouma, Y., Prince-David, M., Delaporte, E., Peeters, M., High rates of virological failure and drug resistance in perinatally HIV-1-infected children and adolescents receiving lifelong antiretroviral therapy in routine clinics in Togo. J. Int. AIDS Soc., 19(1), 2016, 20683.
84. Sax, P.E., DeJesus, E., Mills, A., Zolopa, A., Cohen, C., Wohl, D., Gallant, J.E., Liu, H.C., Zhong, L., Yale, K., White, K., Kearney, B.P., Szwarcberg, J., Quirk, E., Cheng, A.K., team, G.-U.-s., Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir versus co-formulated efavirenz, emtricitabine, and tenofovir for initial treatment of HIV-1 infection: a randomised, double-blind, phase 3 trial, analysis of results after 48 weeks. Lancet 379:9835 (2012), 2439–2448.
85. Seki, T., Suyama-Kagitani, A., Kawauchi-Miki, S., Miki, S., Wakasa-Morimoto, C., Akihisa, E., Nakahara, K., Kobayashi, M., Underwood, M.R., Sato, A., Fujiwara, T., Yoshinaga, T., Effects of raltegravir or elvitegravir resistance signature mutations on the barrier to dolutegravir resistance in vitro. Antimicrob. Agents Chemother. 59:5 (2015), 2596–2606.
86. Simoni, J., Nance, R., Delaney, J.M., Wilson, I.R., Aunon, F., Safren, S.A., Mugavero, M.J., Mayer, K.M., Kithata, M.M., Crane, H.M., Changes in viral, load across US clinics over time. Conf. Retroviruses Oppor. Infect., 2016.
87. Smith, R.A., Raugi, D.N., Pan, C., Sow, P.S., Seydi, M., Mullins, J.I., Gottlieb, G.S., University of Washington-Dakar, H.I.V.S.G. In vitro activity of dolutegravir against wild-type and integrase inhibitor-resistant HIV-2. Retrovirology, 12, 2015, 10.
88. Steigbigel, R.T., Cooper, D.A., Teppler, H., Eron, J.J., Gatell, J.M., Kumar, P.N., Rockstroh, J.K., Schechter, M., Katlama, C., Markowitz, M., Yeni, P., Loutfy, M.R., Lazzarin, A., Lennox, J.L., Clotet, B., Zhao, J., Wan, H., Rhodes, R.R., Strohmaier, K.M., Barnard, R.J., Isaacs, R.D., Nguyen, B.Y., Teamsa, B.S., Long-term efficacy and safety of Raltegravir combined with optimized background therapy in treatment-experienced patients with drug-resistant HIV infection: week 96 results of the BENCHMRK 1 and 2 Phase III trials. Clin. Infect. Dis. 50:4 (2010), 605–612.
89. Theys, K., Abecasis, A., Libin, P., Gomes, P., Cabanas, J., Camacho, R.J., Van Laethem, K., Discordant predictions of residual activity could impact dolutegravir prescription upon raltegravir failure. J. Clin. Virol. 70 (2015), 120–127.
90. Wainberg, M.A., Han, Y.S., Will drug resistance against dolutegravir in initial therapy ever occur?. Front. Pharmacol., 6, 2015, 90.
91. Wainberg, M.A., Mesplede, T., Implications for the future of the HIV epidemic if drug resistance against dolutegravir cannot occur in first-line therapy. J. Int. AIDS Soc., 18, 2015, 20824.
92. Wainberg, M.A., Zaharatos, G.J., Brenner, B.G., Development of antiretroviral drug resistance. N. Engl. J. Med. 365:7 (2011), 637–646.
93. Wainberg, M.A., Mesplede, T., Raffi, F., What if HIV were unable to develop resistance against a new therapeutic agent?. BMC Med., 11, 2013, 249.
94. Walmsley, S.L., Antela, A., Clumeck, N., Duiculescu, D., Eberhard, A., Gutierrez, F., Hocqueloux, L., Maggiolo, F., Sandkovsky, U., Granier, C., Pappa, K., Wynne, B., Min, S., Nichols, G., Investigators, S., Dolutegravir plus abacavir-lamivudine for the treatment of HIV-1 infection. N. Engl. J. Med. 369:19 (2013), 1807–1818.
95. Walmsley, S., Baumgarten, A., Berenguer, J., Felizarta, F., Florence, E., Khuong-Josses, M.A., Kilby, J.M., Lutz, T., Podzamczer, D., Portilla, J., Roth, N., Wong, D., Granier, C., Wynne, B., Pappa, K., Brief report: dolutegravir plus abacavir/lamivudine for the treatment of HIV-1 infection in antiretroviral therapy-naive patients: week 96 and week 144 results from the SINGLE randomized clinical trial. J. Acquir. Immune Defic. Syndr. 70:5 (2015), 515–519.
96. Walmsley, S., Baumgarten, A., Berenguer, J., Felizarta, F., Florence, E., Khuong-Josses, M.A., Kilby, J.M., Lutz, T., Podzamczer, D., Portilla, J., Roth, N., Wong, D., Granier, C., Wynne, B., Pappa, K., Dolutegravir plus abacavir/lamivudine for the treatment of HIV-1 infection in antiretroviral therapy-naive patients: week 96 and week 144 results from the SINGLE randomized clinical trial. J. Acquir. Immune Defic. Syndr., 2015.
97. Wang, C., Mitsuya, Y., Gharizadeh, B., Ronaghi, M., Shafer, R.W., Characterization of mutation spectra with ultra-deep pyrosequencing: application to HIV-1 drug resistance. Genome Res. 17:8 (2007), 1195–1201.
98. Wensing, A.M., Calvez, V., Gunthard, H.F., Johnson, V.A., Paredes, R., Pillay, D., Shafer, R.W., Richman, D.D., Update of the drug resistance mutations in HIV-1. Top. Antivir. Med. 23:4 (2015), 132–141.