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Authors' Reply

Early Initiation of Antiretroviral Therapy Among Young Children

A Long Way to Go

Koller, Manuel DrSc*; Patel, Kunjal DSc, MPH; Chi, Benjamin H. MD; Wools-Kaloustian, Kara MD§; Dicko, Fatoumata MD; Chokephaibulkit, Kulkanya MD; Chimbetete, Cleophas MD#; Hazra, Rohan MD**; Ayaya, Samual MD††; Leroy, Valeriane MD, PhD‡‡; Trong, Huu Khanh MD§§; Egger, Matthias MD*,‖‖; Davies, Mary-Ann MD, PhD‖‖ for the IeDEA, NISDI, PHACS and IMPAACT 219C Studies

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JAIDS Journal of Acquired Immune Deficiency Syndromes: October 1, 2015 - Volume 70 - Issue 2 - p e71-e72
doi: 10.1097/QAI.0000000000000773
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To the Editors:

We thank Doherty and co-workers for their thoughtful and pertinent response to our article describing trends in immunodeficiency at antiretroviral therapy (ART) initiation in children in low, middle, and high income countries.1 We agree that it is important to know more about the International Epidemiologic Databases to Evaluate AIDS (IeDEA) sites included in the analysis to assess the extent to which they are representative of general public health facilities, and hence whether the finding of improvement in proportion of children with immunosuppression at ART initiation (albeit modest) is generalizable across these countries.

The IeDEA collaboration and the participating sites have therefore been described in dedicated profiles,2,3 and a survey of the IeDEA sites providing HIV care for children has been published.4 The survey included 63 sites in Asia (10), Central Africa (4), East Africa (29), Southern Africa (10), and West Africa (10). Nearly 75% of sites were public government-run clinics, 65% were in urban settings, and 57% provided pediatric care in combined adult–pediatric clinics.4 As pointed out by Doherty and co-workers, many sites received additional financial support from research grants (57%), the US PEPFAR programe (54%) or the Global Fund (24%).4 We cannot exclude that access to timely pediatric ART at non-IeDEA facilities may be even worse. However, all IeDEA sites followed the relevant national ART guidelines, and the strength of IeDEA data is that it is collected as part of routine care and not from dedicated research cohorts. We believe that the availability of individualized data through the IeDEA collaboration allowed a more nuanced picture of pediatric ART than analyses of program-level aggregate data, while preventing the ecological bias that may affect aggregate data analyses.5

We concur with Doherty and co-workers regarding the importance of advocacy for pediatric HIV as a neglected disease with an urgent need for better access to diagnostic tests and effective and safe pediatric-friendly drug formulations.6 The first barrier to early ART initiation is poor access to early infant diagnosis for which coverage remains low in many settings due to lack of virological diagnostic capacity, delivery services, and low social acceptability.7,8 Even in IeDEA sites, early infant diagnosis for infants was not universally available throughout the period of data collection, with the diagnosis of HIV being dependent on the presence of clinical symptoms. In the IeDEA site survey, access to certain drugs especially as part of fixed dose combinations was limited in certain regions.4 Interestingly, Asian sites had poorer access to tenofovir and abacavir, which may reflect more frequent eligibility for PEPFAR pricing in sub-Saharan Africa.4 We have also previously found limited access to second-line options for children, which may result in delays or lack of switching to second-line therapy.9,10 Although the dramatically increased coverage and effectiveness of prevention of mother to child transmission programs are to be welcomed, there is a risk of even further neglect of treatment options for children as the market diminishes in size. In addition, the low priority and complexity of conducting research in children mean that there is limited high-quality data from randomized clinical trials to inform optimal pediatric treatment guidelines and drug choices. We strongly endorse the call for better drug options for children, especially for very young infants where treatment options are extremely limited, and we know that there is substantial mortality and morbidity benefit in starting ART before 3 months of age.11


1. Koller M, Patel K, Chi BH, et al.. Immunodeficiency in children starting antiretroviral therapy in low-, middle-, and high-income countries. J Acquir Immune Defic Syndr. 2015;68:62–72.
2. Egger M, Ekouevi DK, Williams C, et al.. Cohort Profile: the international epidemiological databases to evaluate AIDS (IeDEA) in sub-Saharan Africa. Int J Epidemiol. 2011;18:18.
3. McGowan C, Cahn P, Gotuzzo E, et al.. Cohort Profile: Caribbean, Central and South America Network for HIV research (CCASAnet) collaboration within the international epidemiologic databases to evaluate AIDS (IeDEA) programme. Int J Epidemiol. 2007;36:969–976.
4. The International epidemiologic Databases to Evaluate AIDS (IeDEA) Pediatric Collaboration. A survey of paediatric HIV programmatic and clinical management practices in Asia and sub-Saharan Africa-the International epidemiologic Databases to Evaluate AIDS (IeDEA). J Int AIDS Soc. 2013;16:17998.
5. Ford N, Mills E, Egger M. Immunodeficiency at start of antiretroviral therapy: the persistent problem of late presentation to care. Clin Infect Dis. 2015. Available at: Accessed 15 June 2015.
6. Lallemant M, Chang S, Cohen R, et al.. Pediatric HIV–a neglected disease? N Engl J Med. 2011;365:581–583.
7. Ciaranello AL, Park JE, Ramirez-Avila L, et al.. Early infant HIV-1 diagnosis programs in resource-limited settings: opportunities for improved outcomes and more cost-effective interventions. BMC Med. 2011;9:59.
8. UNAIDS. Global Report: UNAIDS Report on the Global AIDS Epidemic 2013. 2013. Available at: Accessed June, 15 2015.
9. Treat-Asia Pediatric HIV Observational Database (TApHOD) and The International Epidemiologic Databases to Evaluate AIDS Southern Africa (IeDEA-SA) Collaboration. A biregional survey and review of first-line treatment failure and second-line paediatric antiretroviral access and use in Asia and southern Africa. J Int AIDS Soc. 2011;14:7.
10. Davies M, Moultrie H, Eley B, et al.. Virologic failure and second-line antiretroviral therapy in children in South Africa: the IeDEA Southern Africa collaboration. J Acquir Immune Defic Syndr. 2011;56:270–278.
11. Violari A, Cotton MF, Gibb DM, et al.. Early antiretroviral therapy and mortality among HIV-infected infants. N Engl J Med. 2008;359:2233–2244.
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