Time to switch to second-line antiretroviral therapy in children with human immunodeficiency virus in Europe and Thailand

Goetghebuer, T.; Hainaut, M.; Van Der Kelen, E.; Delforge, M.; Warszawski, J.; Le Chenadec, J.; Ramos, E.; Dialla, O.; Wack, T.; Laurent, C.; Selmi, L. A.; Leymarie, I.; Benali, F. A.; Brossard, M.; Boufassa, L.; Floch-Tudal, C.; Firtion, G.; Hau, I.; Chace, A.; Bolot, P.; Blanche, S.; Granier, M.; Labrune, P.; Lachassine, E.; Dollfus, C.; Levine, M.; Fourcade, C.; Heller-Roussin, B.; Runel-Belliard, C.; Tricoire, J.; Monpoux, F.; Chirouze, C.; Reliquet, V.; Brouard, J.; Kebaili, K.; Fialaire, P.; Lalande, M.; Mazingue, F.; Partisani, M. L.; Konigs, C.; Schultze-Strasser, S.; Baumann, U.; Niehues, T.; Neubert, J.; Kobbe, R.; Feiterna-Sperling, C.; Konigs, C.; Buchholz, B.; Notheis, G.; Naver, L.; Soeria-Atmadja, S.; Hagas, V.; Scott, S.; Vaughan, Y.; Welch, S.; Laycock, N.; Bernatoniene, J.; Finn, A.; Hutchison, L.; Sharpe, G.; Williams, A.; Lyall, E. G. H.; Seery, P.; Topley, Lewis; Miles, K.; Subramaniam, B.; Hutchinson, L.; Ward, P.; Sloper, K.; Gopal, G.; Doherty, C.; Hague, R.; Price, V.; Bamford, A.; Bundy, H.; Clapson, M.; Flynn, J.; Gibb, D. M.; Klein, N.; Novelli, V.; Shingadia, D.; Ainsley-Walker, P.; Tovey, P.; Gurtin, D.; Garside, J. P.; Fall, A.; Porter, D.; Segal, S.; Ball, C.; Hawkins, S.; Chetcuti, P.; Dowie, M.; Bandi, S.; Mccabe, A.; Eisenhut, M.; Handforth, J.; Roy, P. K.; Flood, T.; Pickering, A.; Liebeschuetz, S.; Kavanagh, C.; Murphy, C.; Rowson, K.; Tan, T.; Daniels, J.; Lees, Y.; Kerr, E.; Thompson, F.; Williams, A.; Le Provost, M.; Cliffe, L.; Smyth, A.; Stafford, S.; Freeman, A.; Reddy, T.; Fidler, K.; Christie, S.; Gordon, A.; Rogahn, D.; Harris, S.; Hutchinson, L.; Collinson, A.; Hutchinson, L.; Jones, L.; Offerman, B.; Van Someren, V.; Benson, C.; Riordan, A.; Riddell, A.; O'Connor, R.; Brown, N.; Ibberson, L.; Shackley, F.; Faust, S. N.; Hancock, J.; Doerholt, K.; Donaghy, S.; Prime, K.; Sharland, M.; Storey, S.; Gorman, S.; Lyall, E. G. H.; Monrose, C.; Seery, P.; Tudor-Williams, G.; Walters, S.; Cross, R.; Menson, E.; Broomhall, J.; Hutchinson, L.; Scott, D.; Stroobant, J.; Bridgwood, A.; Mcmaster, P.; Evans, J.; Gardiner, T.; Jones, R.; Gardiner, K.; Giaquinto, C.

doi:10.1093/cid/cix854

Background. Data on durability of first-line antiretroviral therapy (ART) in children with human immunodeficiency virus (HIV) are limited. We assessed time to switch to second-line therapy in 16 European countries and Thailand. Methods. Children aged <18 years initiating combination ART (.2 nucleoside reverse transcriptase inhibitors [NRTIs] plus nonnucleoside reverse transcriptase inhibitor [NNRTI] or boosted protease inhibitor [PI]) were included. Switch to second-line was defined as (i) change across drug class (PI to NNRTI or vice versa) or within PI class plus change of .1 NRTI; (ii) change from single to dual PI; or (iii) addition of a new drug class. Cumulative incidence of switch was calculated with death and loss to follow-up as competing risks. Results. Of 3668 children included, median age at ART initiation was 6.1 (interquartile range (IQR), 1.7.10.5) years. Initial regimens were 32% PI based, 34% nevirapine (NVP) based, and 33% efavirenz based. Median duration of follow-up was 5.4 (IQR, 2.9.8.3) years. Cumulative incidence of switch at 5 years was 21% (95% confidence interval, 20%.23%), with significant regional variations. Median time to switch was 30 (IQR, 16.58) months; two-thirds of switches were related to treatment failure. In multivariable analysis, older age, severe immunosuppression and higher viral load (VL) at ART start, and NVP-based initial regimens were associated with increased risk of switch. Conclusions. One in 5 children switched to a second-line regimen by 5 years of ART, with two-thirds failure related. Advanced HIV, older age, and NVP-based regimens were associated with increased risk of switch.