Gaps in health outcomes for adolescents with HIV but treatment expanding

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Research highlights significant gaps in health outcomes for adolescents born with HIV across the world – but paints a hopeful picture for the future as treatment access expands.

The first global comparison of health outcomes for adolescents living with HIV acquired through mother-to-child transmission has been published and the results shed light on the extent to which health inequalities still exist among adolescents across the world, despite antiretroviral treatment (ART) having greatly reduced inequality among adult and child populations.

Through a retrospective longitudinal analysis, researchers compared treatment outcomes among adolescent populations across five regions worldwide: North America, Europe, sub-Saharan Africa, South and Southeast Asia and South America and the Caribbean.

In using retrospective data, the study sample was also able to compare adolescents who were born with HIV at different periods of time, dividing participants into those born prior to 1995, between 1995 and 1999 and those born between 2000 and 2005. With a cohort of over 38,000 adolescents, the study provides the largest analysis of global HIV epidemiology among this age group.

Some of the poorest health outcomes were found in sub-Saharan Africa. The average age of children from sub-Saharan Africa starting antiretroviral treatment was 7.9 years compared to 0.9 in North America.

The researchers found that there was a strong link between a country’s income and the health outcomes of the adolescents born with HIV. Those living in higher income countries had the lowest mortality and were starting ART younger. They also had higher CD4 counts and less impaired height when they started treatment.

The geographical findings reflect these economic trends, with results showing adolescents in North America and Europe having better health outcomes. Here, they entered into HIV care earlier, started ART younger and had less impaired height.

At 15 years of age, the average global incidence of mortality was 15.6%. However, there was a lot of variation across the regions. Sub-Saharan Africa, South and Southeast Asia and South America and the Caribbean had higher rates of mortality than other regions.
Comparisons by birth year provided some evidence that mortality was decreasing among adolescent populations. Those born later (2000-2005) were more likely to have started ART earlier and had much lower mortality rates than the older cohort. None of the study participants born between 2000 and 2005 in Europe, North America or South America and the Caribbean had died.

The study also investigated rates of loss to follow up, as adherence and staying in care has been identified as one of the key challenges in treating an adolescent population who are transitioning from paediatric to adult care. They found that loss to follow up was lowest in South America and the Caribbean, at 4.4%, and highest in sub-Saharan Africa, at 13.2%.

The study was part of the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER), an ongoing global project that seeks to understand epidemiological factors among adolescents living with HIV. It helps develop a better understanding of the factors at play in adolescent populations that cannot be explained by treatment alone.

The researcher’s comment that, as more “children with HIV acquired around the time of birth or through breastfeeding (perinatally acquired HIV) are surviving into adolescence… better understanding is required to inform the appropriate policy responses to meet the needs of this dynamic and complex population… There is still much work to be done to achieve equality in health and survival for all adolescents living with perinatally acquired HIV, irrespective of geographic location.”

Background: Globally, the population of adolescents living with perinatally acquired HIV (APHs) continues to expand. In this study, we pooled data from observational pediatric HIV cohorts and cohort networks, allowing comparisons of adolescents with perinatally acquired HIV in “real-life” settings across multiple regions. We describe the geographic and temporal characteristics and mortality outcomes of APHs across multiple regions, including South America and the Caribbean, North America, Europe, sub-Saharan Africa, and South and Southeast Asia.
Methods and findings: Through the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER), individual retrospective longitudinal data from 12 cohort networks were pooled. All children infected with HIV who entered care before age 10 years, were not known to have horizontally acquired HIV, and were followed up beyond age 10 years were included in this analysis conducted from May 2016 to January 2017. Our primary analysis describes patient and treatment characteristics of APHs at key time points, including first HIV-associated clinic visit, antiretroviral therapy (ART) start, age 10 years, and last visit, and compares these characteristics by geographic region, country income group (CIG), and birth period. Our secondary analysis describes mortality, transfer out, and lost to follow-up (LTFU) as outcomes at age 15 years, using competing risk analysis. Among the 38,187 APHs included, 51% were female, 79% were from sub-Saharan Africa and 65% lived in low-income countries. APHs from 51 countries were included (Europe: 14 countries and 3,054 APHs; North America: 1 country and 1,032 APHs; South America and the Caribbean: 4 countries and 903 APHs; South and Southeast Asia: 7 countries and 2,902 APHs; sub-Saharan Africa, 25 countries and 30,296 APHs). Observation started as early as 1982 in Europe and 1996 in sub-Saharan Africa, and continued until at least 2014 in all regions. The median (interquartile range [IQR]) duration of adolescent follow-up was 3.1 (1.5–5.2) years for the total cohort and 6.4 (3.6–8.0) years in Europe, 3.7 (2.0–5.4) years in North America, 2.5 (1.2–4.4) years in South and Southeast Asia, 5.0 (2.7–7.5) years in South America and the Caribbean, and 2.1 (0.9–3.8) years in sub-Saharan Africa. Median (IQR) age at first visit differed substantially by region, ranging from 0.7 (0.3–2.1) years in North America to 7.1 (5.3–8.6) years in sub-Saharan Africa. The median age at ART start varied from 0.9 (0.4–2.6) years in North America to 7.9 (6.0–9.3) years in sub-Saharan Africa. The cumulative incidence estimates (95% confidence interval [CI]) at age 15 years for mortality, transfers out, and LTFU for all APHs were 2.6% (2.4%–2.8%), 15.6% (15.1%–16.0%), and 11.3% (10.9%–11.8%), respectively. Mortality was lowest in Europe (0.8% [0.5%–1.1%]) and highest in South America and the Caribbean (4.4% [3.1%–6.1%]). However, LTFU was lowest in South America and the Caribbean (4.8% [3.4%–6.7%]) and highest in sub-Saharan Africa (13.2% [12.6%–13.7%]). Study limitations include the high LTFU rate in sub-Saharan Africa, which could have affected the comparison of mortality across regions; inclusion of data only for APHs receiving ART from some countries; and unavailability of data from high-burden countries such as Nigeria.
Conclusion: To our knowledge, our study represents the largest multiregional epidemiological analysis of APHs. Despite probable under-ascertained mortality, mortality in APHs remains substantially higher in sub-Saharan Africa, South and Southeast Asia, and South America and the Caribbean than in Europe. Collaborations such as CIPHER enable us to monitor current global temporal trends in outcomes over time to inform appropriate policy responses.

The Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) Global Cohort Collaboration

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