Virological outcomes after anti-retroviral therapy initiation among a cohort of children in Canada

Background: The first wave of HIV-infected children to be treated with optimal combination ART (cART) in the developed world setting has now reached adolescence. Little is known on the virological outcomes among this group. The objective of this study is to assess time to virological failure (VF) and treatment interruption (TI) among HIV infected children initiating treatment in the province of Quebec, Canada.
Methods: Study subjects were enrolled in the Centre Maternel et Infantile sur le Sida (CMIS) cohort between 1997 and 2010. HIV-1 plasma RNA levels were measured every three months after cART initiation using the versant HIV-1 RNA assay (Bayer, Pittsburg). Primary outcome was time to first VF, defined as detectable viremia over two consecutive measurements after an initial response to cART, and TI, defined as cessation of HAART for more than 6 months at any time after initiation.
Results: Among the 174 children followed at CMIS during the entire study period, only 45 initiated cART at our center. Median follow-up time was 37.8 (IQR 19.2-59.4) months, median time to first VF was 32 months (IQR 14-44); cumulative incidence of VF at 24, 48 and 96 months of follow-up was 28%, 51%, and 79% respectively. Median time to TI was 52.2 months (IQR 24-72 months), cumulative incidence of TI at 24, 48 and 96 months was 11.8%, 20.4% and 51.13% respectively. Girls were more likely than boys to experience a TI (HR 3.84, 95% CI 1.38-10.10). Children initiated on cART during infancy were more likely to experience VF compared to those initiating treatment after twelve months of age (HR 3.03, 95% CI 1.38-6.72). Among all treated patients (n=108), including those receiving prior sequential mono-bi ART therapy, only 64% had achieved at least I year of sustained virological suppression at any time during their follow-up.
Conclusions: In this cohort of HIV infected children initiating cART in Canada with close monitoring, over 50% experienced VF within 4 years of cART initiation, and over 50% had a TI at some point during their follow-up. These results are concerning given recommendations for life-long therapy in children, and the limited therapeutic options available.

F. Kakkar1, V. Lamarre1, M. Francois2, V. Silvie2, H. Soudeyns3, N. Lapointe2
1CHU Sainte Justine, Infectious Diseases, Montreal, Canada, 2CHU Sainte-Justine, Centre Maternel et Infantile sur le Sida, Montreal, Canada, 3CHU Sainte-Justine, University of Montreal, Microbiology and Immunology, Montreal, Canada