High levels of pre-treatment HIV drug resistance and treatment failure in Nigerian children.
Pre-treatment HIV drug resistance (PDR) is an increasing problem in sub-Saharan Africa. Children are an especially vulnerable population to develop PDR given that paediatric second-line treatment options are limited. Although monitoring of PDR is important, data on the paediatric prevalence in sub-Saharan Africa and its consequences for treatment outcomes are scarce. We designed a prospective paediatric cohort study to document the prevalence of PDR and its effect on subsequent treatment failure in Nigeria, the country with the second highest number of HIV-infected children in the world.



HIV-1-infected children ≤12 years, who had not been exposed to drugs for the prevention of mother-to-child transmission (PMTCT), were enrolled between 2012 and 2013, and followed up for 24 months in Lagos, Nigeria. Pre-antiretroviral treatment (ART) population-basedpolgenotypic testing and six-monthly viral load (VL) testing were performed. Logistic regression analysis was used to assess the effect of PDR (World Health Organization (WHO) list for transmitted drug resistance) on subsequent treatment failure (two consecutive VL measurements >1000 cps/ml or death).



Of the total 82 PMTCT-naïve children, 13 (15.9%) had PDR. All 13 children harboured non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations, of whom seven also had nucleoside reverse transcriptase inhibitor resistance. After 24 months, 33% had experienced treatment failure. Treatment failure was associated with PDR and a higher log VL before treatment initiation (adjusted odds ratio (aOR) 7.53 (95%CI 1.61-35.15) and 2.85 (95%CI 1.04-7.78), respectively).



PDR was present in one out of six Nigerian children. These high numbers corroborate with recent findings in other African countries. The presence of PDR was relevant as it was the strongest predictor of first-line treatment failure.



Our findings stress the importance of implementing fully active regimens in children living with HIV. This includes the implementation of protease inhibitor (PI)-based first-line ART, as is recommended by the WHO for all HIV-infected children <3 years of age. Overcoming practical barriers to implement PI-based regimens is essential to ensure optimal treatment for HIV-infected children in sub-Saharan Africa. In countries where individual VL or resistance testing is not possible, more attention should be given to paediatric PDR surveys.
Amsterdam Institute for Global Health and Development & Department of Global Health, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.|Global Child Health Group, Emma Children's Hospital, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands; r.boerma@aighd.org.
Ragna S
RS
Boerma
Amsterdam Institute for Global Health and Development & Department of Global Health, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.|Global Child Health Group, Emma Children's Hospital, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.|Stichting HIV Monitoring, Amsterdam, The Netherlands.
T Sonia
TS
Boender
Amsterdam Institute for Global Health and Development & Department of Global Health, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.|Division of Infectious Diseases, Department of Internal Medicine, Leiden University Medical Centre, Leiden, The Netherlands.
Kim C E
KC
Sigaloff
Amsterdam Institute for Global Health and Development & Department of Global Health, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
Tobias F
TF
Rinke de Wit
Global Child Health Group, Emma Children's Hospital, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
Michael Boele
MB
van Hensbroek
Institute of Human Virology Nigeria, Abuja, Nigeria.
Nicaise
N
Ndembi
Lagos University Teaching Hospital, University of Lagos, Lagos, Nigeria.
Titilope
T
Adeyemo
Lagos University Teaching Hospital, University of Lagos, Lagos, Nigeria.
Edamisan O
EO
Temiye
Lagos University Teaching Hospital, University of Lagos, Lagos, Nigeria.
Akin
A
Osibogun
Amsterdam Institute for Global Health and Development & Department of Global Health, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
Pascale
P
Ondoa
Global Child Health Group, Emma Children's Hospital, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.|Department of Paediatric Intensive Care, Emma Children's Hospital, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
Job C
JC
Calis
Lagos University Teaching Hospital, University of Lagos, Lagos, Nigeria.
Alani Sulaimon
AS
Akanmu
D017954:Africa South of the Sahara / Q000453:epidemiology; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D002648:Child; D015331:Cohort Studies; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000517:prevention & control*; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D009549:Nigeria; D015995:Prevalence; D011446:Prospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D017211:Treatment Failure; D019562:Viral Load / Q000187:drug effects
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors
HIV drug resistance; HIV-1; PMTCT; genotypic resistance testing; paediatric; sub-Saharan Africa