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Time to First-Line ART Failure and Time to Second-Line ART Switch in the IeDEA Pediatric Cohort

Wools-Kaloustian, Kara, MS, MD*; Marete, Irene, MBCHB, MMED; Ayaya, Samuel, MBCHB, MMED; Sohn, Annette, H., MD; Van Nguyen, Lam, MD, PhD§; Li, Shanshan, PhD; Leroy, Valériane, MD, PhD; Musick, Beverly, S., MS#; Newman, Jamie, E., PhD**; Edmonds, Andrew, MSPH, PhD††; Davies, Mary-Ann, MBChB, PhD‡‡; Eboua, François, T., MD§§; Obama, Marie-Thérèse, MD‖‖; Yotebieng, Marcel, MD¶¶; Sawry, Shobna, MSc(Med)##; Mofenson, Lynne, M., MD***; Yiannoutsos, Constantin, T., PhD

JAIDS Journal of Acquired Immune Deficiency Syndromes: June 1, 2018 - Volume 78 - Issue 2 - p 221–230
doi: 10.1097/QAI.0000000000001667
Clinical Science

Background: Globally, 49% of the estimated 1.8 million children living with HIV are accessing antiretroviral therapy (ART). There are limited data concerning long-term durability of first-line ART regimens and time to transition to second-line.

Methods: Children initiating their first ART regimen between 2 and 14 years of age and enrolled in one of 208 sites in 30 Asia-Pacific and African countries participating in the Pediatric International Epidemiology Databases to Evaluate AIDS consortium were included in this analysis. Outcomes of interest were: first-line ART failure (clinical, immunologic, or virologic), change to second-line, and attrition (death or loss to program ). Cumulative incidence was computed for first-line failure and second-line initiation, with attrition as a competing event.

Results: In 27,031 children, median age at ART initiation was 6.7 years. Median baseline CD4% for children ≤5 years of age was 13.2% and CD4 count for those >5 years was 258 cells per microliter. Almost all (94.4%) initiated a nonnucleoside reverse transcriptase inhibitor; 5.3% a protease inhibitor, and 0.3% a triple nucleoside reverse transcriptase inhibitor–based regimen. At 1 year, 7.7% had failed and 14.4% had experienced attrition; by 5 years, the cumulative incidence was 25.9% and 29.4%, respectively. At 1 year after ART failure, 13.7% had transitioned to second-line and 11.2% had experienced attrition; by 5 years, the cumulative incidence was 31.6% and 25.9%, respectively.

Conclusions: High rates of first-line failure and attrition were identified in children within 5 years after ART initiation. Of children meeting failure criteria, only one-third were transitioned to second-line ART within 5 years.

*Department of Medicine, Indiana University School of Medicine, Indianapolis, IN;

Deptartment of Child Health and Pediatrics, School of Medicine, Moi University, Eldoret, Kenya;

TREAT Asia/amfAR—The Foundation for AIDS Research, Bangkok, Thailand;

§Department of Infectious Diseases, National Hospital of Pediatrics, Hanoi, Vietnam;

Department of Epidemiology, Fairbanks School of Public Health, Indianapolis, IN;

**Inserm U1027, Toulouse 3 University, Toulouse, France;

#Department of Biostatistics, Indiana University School of Medicine, Indianapolis, IN;

**RTI International, Public Health Informatics Program, Research Triangle Park, NC;

††Department of Epidemiology, Gillings School of Global Public Health, The University of North Carolina, Chapel Hill, NC;

‡‡Centre for Infectious Disease Epidemiology and Research, University of Cape Town, Cape Town, South Africa;

§§Department of Pediatrics, Centre Hospitalier Universitaire de Yopougon, Abidjan, Côte d'Ivoire;

‖‖Département de pédiatrie, Centre Hospitalier et Universitaire, Yaoundé, Cameroon;

¶¶Division of Epidemiology, College of Public Health, Ohio State University, Columbus, OH;

##Wits Reproductive Health and HIV Institute, University of the Witwatersrand, School of Clinical Medicine, Johannesburg, South Africa; and

***Elizabeth Glaser Pediatric AIDS Foundation, Washington DC.

Correspondence to: Kara Wools-Kaloustian, MS, MD, 545 Barnhill Dr. Suite EH421, Indianapolis, IN (e-mail:

Supported through grants from the National Institutes of Health through the National Institute of Allergy and Infectious Diseases and the Eunice Kennedy Shriver National Institute of Child Health and Human Development under the following grants: East Africa IeDEA (U01 AI069911), IeDEA Asia-Pacific (U01 AI069907), IeDEA West Africa (U01 AI069919), IeDEA Southern Africa (U01 AI069924), IeDEA Central Africa 1.0 (U01 AI069927), and IeDEA Central Africa 2.0 (U01 AI096299).

Presented at the 6th International Workshop on HIV Pediatrics; July 18–19, 2014; Melbourne, Australia.

The authors have no funding or conflicts of interest to disclose.

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Received September 08, 2017

Accepted February 05, 2018

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