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


CONCLUSIONS
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.
Louise
L
Kuhn
Gillian
G
Hunt
Karl-Günter
KG
Technau
Ashraf
A
Coovadia
Johanna
J
Ledwaba
Sam
S
Pickerill
Martina
M
Penazzato
Silvia
S
Bertagnolio
Claude A
CA
Mellins
Vivian
V
Black
Lynn
L
Morris
Elaine J
EJ
Abrams
D019380:Anti-HIV Agents / Q000627:therapeutic use; D018890:Chemoprevention / Q000379:methods; D024882:Drug Resistance, Viral; D005260:Female; D006678:HIV / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification*; D015658:HIV Infections / Q000517:prevention & control / Q000821:virology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D010949:Plasma / Q000821:virology; D011247:Pregnancy; D015995:Prevalence; D012367:RNA, Viral / Q000235:genetics*; D013019:South Africa / Q000453:epidemiology
D019380:Anti-HIV Agents; D012367:RNA, Viral