Time to switch to second-line antiretroviral therapy in children with HIV in Europe and Thailand

25 Mar, 2018

Authors: European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) Study Group in EuroCoord.

Published in: Clin Infect Dis. 2018;66(4):594-603.

Background Global data on durability of first-line antiretroviral therapy (ART) in children with HIV is limited. We assessed time to switch to second-line therapy in 16 European countries and Thailand.

Methods Children <18-years initiating combination ART (≥2 nucleoside reverse transcriptase inhibitor (NRTI) plus non-NRTI (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 3,668 children included, median [IQR] age at ART initiation was 6.1 [1.7,10.5] years. Initial regimens were 32% PI, 34% nevirapine (NVP), 33% efavirenz-based. Median duration of follow-up from ART start was 5.4 [2.9,8.3] years. Cumulative incidence of switch at 5 years was 21% (95% CI 20, 23), with lowest incidence in Russia/Ukraine and highest in UK/Ireland. Median time to switch was 30 [15, 58] months, two-thirds of switches were related to treatment failure. In multivariable analysis, older age, severe immunosuppression and higher viral load at ART start, and NVP-based initial regimens were associated with increased risk of switch. Among those switched, 65% had viral load <400c/mL at 12-months after start of second-line ART.

Conclusions One in five children switched to second-line 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.