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Drug resistance among newly diagnosed HIV-infected children in the era of more efficacious antiretroviral prophylaxis

Kuhn, Louisea; Hunt, Gillianb; Technau, Karl-Günterc; Coovadia, Ashrafc; Ledwaba, Johannab; Pickerill, Samc; Penazzato, Martinad; Bertagnolio, Silviae; Mellins, Claude A.f; Black, Viviang; Morris, Lynnb; Abrams, Elaine J.h

doi: 10.1097/QAD.0000000000000261
Epidemiology and Social: Concise Communication

Background: In the era of more efficacious prevention of mother-to-child transmission (PMTCT) regimens, documenting the profile of drug resistance in HIV-infected infants and young children is critical to our efforts to improve care and treatment for children.

Methods: HIV drug resistance mutations in plasma virus were ascertained using population sequencing among 230 newly diagnosed HIV-infected children under 2 years of age recruited in Johannesburg, South Africa, during 2011. By this time, more effective PMTCT regimens, including combination antiretroviral therapy for pregnant women, were being implemented.

Results: Two-thirds (67.4%) of HIV-infected children had been exposed to some form of maternal (89%) and/or infant (97%) PMTCT. Among PMTCT-exposed, 56.8% had nonnucleoside reverse transcriptase inhibitor (NNRTI), 14.8% nucleoside reverse transcriptase inhibitor (NRTI), and 1.3% protease inhibitor mutations. NNRTI mutations were strongly related to younger age. The remaining third (32.6%) had no reported or recorded PMTCT exposures, but resistance to NNRTI was detected in 24.0%, NRTI in 10.7%, and protease inhibitor in 1.3%.

Conclusion: The new PMTCT strategies dramatically reduce the number of children who acquire infection, but among those who do become infected, NNRTI resistance prevalence is high. In this South African setting with high PMTCT coverage, almost a quarter of children with no reported or recorded PMTCT also have drug resistance mutations. PMTCT history is an inadequate means of ruling out pretreatment drug resistance. Our results support the use of protease inhibitor-based first-line regimens in HIV-infected infants and young children regardless of PMTCT history.

aGertrude H. Sergievsky Center, College of Physicians and Surgeons, and Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, USA

bNational Institute for Communicable Diseases of the National Health Laboratory Services

cFaculty of Health Sciences, Empilweni Services and Research Unit, Department of Paediatrics & Child Health, Rahima Moosa Mother and Child Hospital, University of the Witwatersrand, Johannesburg, South Africa

dMRC Clinical Trial Unit, University College London, London, UK

eHIV Department, World Health Organization, Geneva, Switzerland

fHIV Center for Clinical and Behavioral Studies in the Division of Gender Sexuality and Health, Department of Psychiatry, Columbia University and the New York State Psychiatric Institute, New York, New York, USA

gFaculty of Health Sciences, Wits Reproductive Health and HIV Institute, University of Witwatersrand, Johannesburg, South Africa

hICAP, Mailman School of Public Health, and Department of Pediatrics, College of Physicians & Surgeons, Columbia University, New York, New York, USA.

Correspondence to Louise Kuhn, PhD, Gertrude H. Sergievsky Center, Columbia University, 630 W 168th Street, New York, NY 10032, USA. E-mail: lk24@cumc.columbia.edu

Received 2 January, 2014

Revised 12 February, 2014

Accepted 12 February, 2014

© 2014 Lippincott Williams & Wilkins, Inc.