Outcomes on ART among children and adolescents in Latin America

Mortality in children with human immunodeficiency virus initiating treatment: a six-cohort study in Latin America.

Luque MT, Jenkins CA, Shepherd BE, Padgett D, Rouzier V, Succi RC, Machado DM, McGowan CC, Vermund SH, Pinto JA. J Pediatr. 2017 Jan 9. pii: S0022-3476(16)31433-0. doi: 10.1016/j.jpeds.2016.12.034. [Epub ahead of print]

Objectives: To assess the risks of and factors associated with mortality, loss to follow-up, and changing regimens after children with HIV infected perinatally initiate combination antiretroviral therapy (cART) in Latin America and the Caribbean.

Study design: This 1997-2013 retrospective cohort study included 1174 antiretroviral therapy-naive, perinatally infected children who started cART when they were younger than 18 years of age (median 4.7 years; IQR 1.7-8.8) at 1 of 6 cohorts from Argentina, Brazil, Haiti, and Honduras, within the Caribbean, Central and South America Network for HIV Epidemiology. Median follow-up was 5.6 years (IQR 2.3-9.3). Study outcomes were all-cause mortality, loss to follow-up, and major changes/interruption/stopping of cART. We used Cox proportional hazards models stratified by site to examine the association between predictors and times to death or changing regimens.

Results: Only 52% started cART at younger than 5 years of age; 19% began a protease inhibitor. At cART initiation, median CD4 count was 472 cells/mm3 (IQR 201-902); median CD4% was 16% (IQR 10-23). Probability of death was high in the first year of cART: 0.06 (95% CI 0.04-0.07). Five years after cART initiation, the cumulative mortality incidence was 0.12 (95% CI 0.10-0.14). Cumulative incidences for loss to follow-up and regimen change after 5 years were 0.16 (95% 0.14-0.18) and 0.30 (95% 0.26-0.34), respectively. Younger children had the greatest risk of mortality, whereas older children had the greatest risk of being lost to follow-up or changing regimens.

Conclusions: Innovative clinical and community approaches are needed for quality improvement in the pediatric care of HIV in the Americas.

Abstract access [1]

Editor’s notes: Despite the dramatic declines in mortality with antiretroviral therapy (ART), mortality rates among children living with HIV still remain substantially higher than in the general paediatric population in high-income settings, such as in the United States of America. Mortality rates after ART initiation are even higher in sub-Saharan Africa, likely because children initiate ART at older ages and at more advanced stages of disease. There are, however, no data available for Latin America and the Caribbean, which has had a mostly stable epidemic with a slowly declining adult HIV incidence over the past decade.

In this retrospective cohort study, the authors investigate mortality, loss-to-follow-up (LTFU) and regimen change among children who acquired HIV in the perinatal period from Argentina, Haiti, Honduras and Brazil. They initiated ART aged below 18 years. About half of all children started ART aged over five years, and a third had clinical AIDS by the time they initiated ART. This would suggest that paediatric HIV programmes in this region face similar challenges to those seen in African programmes, including failure of prevention of mother-to-child HIV transmission (PMTCT) programmes and late diagnosis of children.

As expected, a low baseline CD4 count and clinical AIDS at baseline were both associated with an increased risk of mortality. Importantly, younger age at starting ART was also associated with an increased hazard of death, as was being an adolescent (although the association was weaker). The most likely reason for this is that the youngest children placed on ART may have been initiated following presentation with fast-progressing disease, and would therefore have a higher risk of death than comparatively healthier and stable older children. The higher risk of death among the adolescents likely reflects delayed diagnosis of slow-progressors in adolescence.   

Another important finding was the significantly higher risk of LTFU and regimen change in adolescents compared to younger children. This finding, also noted in African and high-income setting cohorts, highlights the challenges of retaining adolescents in care, addressing treatment fatigue, and possibly increased risk of attrition from care during transitioning from paediatric to adult services. 

In summary, HIV care outcomes in children in Latin America and the Caribbean appear to be similar to those reported in other settings. Together, they highlight the pressing need for strengthening prevention of mother-to-child HIV transmission programmes, particularly follow-up and prompt testing of HIV-exposed infants. It also emphasizes the need for innovative approaches to support children to stay in care and maintain long-term adherence. 

Latin America [7]
Argentina [8], Brazil [9], Haiti [10], Honduras [11]
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