Factors beyond ART play role in the health of sub-Saharan HIV+ adolescents

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Adolescents who acquired HIV perinatally were less likely to die, grew faster and had better immune restoration on treatment if they lived in upper-middle income countries in sub-Saharan Africa, a comparative study presented at the 9th International AIDS Society Conference on HIV Science (IAS 2017) reported.

Of adolescents who had ever received antiretroviral therapy (ART), those in low- and lower-middle income countries had a two-and-a-half- to three-fold greater risk of death than adolescents in upper-middle income countries.

The results suggest that factors beyond the ART programme still play an important role in the health and wellbeing of adolescents with perinatally acquired HIV, Dr Amy Slogrove, presenting on behalf of the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) Global Cohort Collaboration Adolescent Project Team said.
While global access to antiretrovirals is expanding, the emerging population of adolescents with perinatally acquired HIV continues to grow. 80% of adolescents living with perinatally or behaviourally acquired HIV live in sub-Saharan Africa. This is a complex region marked by diversity and inequality.

Expanding upon their previous analysis (presented at IAS 2016) the researchers from University of Cape Town, Centre for Infectious Disease and Epidemiologic Research, Universite Paul Sabatier Toulouse, INSERM U1027, Toulouse, University College London, and MRC Clinical Trials Unit, London, looked at the outcomes of adolescents with perinatally acquired HIV according to country income group in sub-Saharan Africa. Their first analysis showed adolescents in sub-Saharan Africa had a two- to four-fold greater risk of death compared to adolescents in Europe, North America and South and Southeast Asia.

Through the CIPHER cohort collaboration individual retrospective data from 12 cohort networks across five continents were pooled. This analysis includes seven networks representing 25 countries in sub-Saharan Africa.

An adolescent with perinatally acquired HIV included in this analysis is defined as a child having entered care before the age of 10 with no known non-vertical route of HIV infection and having been followed after the age of 10.

Country income group was determined according to World Bank classification at the median year of the first visit by country. Of the 30,296 adolescents included in the analysis 75.7% lived in low-income countries (LIC), close to 5% in lower-middle income countries (LMIC) and almost 20% in upper-middle income countries (UMIC). The cohort accumulated a total of 78,619 person-years of follow-up between 10 and 19 years of age.

Approximately two-thirds were born in or after 2000. The median age at the start of ART was 8 (IQR: 6-9) years and at the last follow-up the median age was 12 (IQR: 11-14) years and was comparable in all country income groups.

Out of approximately half (15,254) of adolescents with perinatally acquired HIV with CD4 cell counts at the start of ART the median ranged from 310 (IQR: 165-520) cells/mm3 in LIC to 292 (IQR: 174-417) cells/mm3 and 318 (IQR: 162-558) cells/mm3 in LMIC and UMIC, respectively. However, the mean CD4 cell count change between ART start and last visit was greatest in the LMIC, followed by UMIC and LIC, at 463 cells/mm3, 353 cells/mm3 and 295 cells/mm3, respectively.

Of just over half (16,181) with height-for-age Z score (HAZ) at the start of ART the median was -2.01, -2.08 and -2.02 for LIC, LMIC and UMIC, respectively (a HAZ of <-2 indicates that most of the children were already stunted at ART start).

The greatest improvement in height was seen in adolescents in UMIC followed by LIC and LMIC at 0.44, 0.16 and 0.04 mean Z-scores, respectively. The cumulative incidence of death between the ages of 10 and 15 was similar in LIC and LMIC but lowest in UMIC, at 3.5% (95% CI: 3.1-3.8, p < 0.001) 3.9% (95%CI: 2.7-5.4) and 1.1% (95% CI: 0.8-1.4) p < 0.001, respectively,

While 85.9% (26,018) ever started ART and 12.5% (3352) started at or above 10 years of age, the differences between country income groups varied significantly. Of the 75% (22,925) living in LIC, 83.4% (19,114) had ever started ART compared to 87.1% (1207) and 95.2% (5697) in LMIC and UMIC, p < 0.001, respectively.

More than double the number of children in LIC started ART at or above the age of 10 compared to those in UMIC and approximately 25% more compared to those in LMIC, 14.8% (2829), 6.7% (382) and 11.7% (141), p < 0.001, respectively.

Abstract
Background: Eighty percent of adolescents living with perinatally- and behaviourally-acquired HIV live in sub-Saharan Africa (SSA), a continent with marked economic inequality. Extending our previous global description of adolescents living with perinatally-acquired HIV (APH), this analysis aimed to describe APH outcomes in SSA by country income group (CIG).
Methods: Through the CIPHER cohort collaboration, individual retrospective data from 12 cohort networks across 5 continents were pooled; 7 networks representing SSA were included here. APH included were HIV-infected children with entry into care at age < 10 years (proxy for perinatally-acquired HIV), and follow-up at age >10 years. CIG was classified according to World Bank classification at median year of first visit by country. Cumulative incidence functions were calculated by competing risks analysis for mortality, transfer-out and loss-to-follow-up.
Results: 30,296 APH were included; 75.7% resident in low income countries (LIC), 4.6% in lower-middle income countries (LMIC) and 19.8% in upper-middle income countries (UMIC). 64% of APH were born ≥2000. Median (interquartile range [IQR]) age at antiretroviral therapy (ART) start (8 [6;9] years) and at last follow-up (12 [11;14] years) were equivalent across CIG. 26,018 (85.9%) ever started ART and 3,352 (12.5%) started at age >10 years, both significantly different between CIG (p< 0.001) (Table 1). Individual CD4 count improved between ART start and last visit in all CIG (p< 0.001). Half of APH had height-for-age Z-score (HAZ) < -2 at ART start that improved by last visit in LIC (p< 0.001) and UMIC (p< 0.001) but not LMIC (p=0.18). Mortality between age 10-15 years was lowest in UMIC however loss-to-follow-up was highest in UMIC.
Conclusions: Despite starting ART late, improvements in height and CD4 count were observed in most APH surviving to adolescence. Mortality rates are likely under-estimated. However, results highlight inequalities in mortality and access to ART according to CIG in SSA.

Authors
A Slogrove, V Leroy, A Judd

Aidsmap material
IAS 2017 abstract


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