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High levels of pre-treatment HIV drug resistance and treatment failure in Nigerian children.
J Int AIDS Soc. 2016; 19(1):21140.JI

Abstract

INTRODUCTION

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.

METHODS

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-based pol genotypic 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).

RESULTS

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).

DISCUSSION

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.

CONCLUSIONS

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.

Authors+Show Affiliations

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.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.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.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.Institute of Human Virology Nigeria, Abuja, Nigeria.Lagos University Teaching Hospital, University of Lagos, Lagos, Nigeria.Lagos University Teaching Hospital, University of Lagos, Lagos, Nigeria.Lagos University Teaching Hospital, University of Lagos, Lagos, Nigeria.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. Department of Paediatric Intensive Care, Emma Children's Hospital, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.Lagos University Teaching Hospital, University of Lagos, Lagos, Nigeria.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27836020

Citation

Boerma, Ragna S., et al. "High Levels of Pre-treatment HIV Drug Resistance and Treatment Failure in Nigerian Children." Journal of the International AIDS Society, vol. 19, no. 1, 2016, p. 21140.
Boerma RS, Boender TS, Sigaloff KC, et al. High levels of pre-treatment HIV drug resistance and treatment failure in Nigerian children. J Int AIDS Soc. 2016;19(1):21140.
Boerma, R. S., Boender, T. S., Sigaloff, K. C., Rinke de Wit, T. F., van Hensbroek, M. B., Ndembi, N., Adeyemo, T., Temiye, E. O., Osibogun, A., Ondoa, P., Calis, J. C., & Akanmu, A. S. (2016). High levels of pre-treatment HIV drug resistance and treatment failure in Nigerian children. Journal of the International AIDS Society, 19(1), 21140. https://doi.org/10.7448/IAS.19.1.21140
Boerma RS, et al. High Levels of Pre-treatment HIV Drug Resistance and Treatment Failure in Nigerian Children. J Int AIDS Soc. 2016;19(1):21140. PubMed PMID: 27836020.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - High levels of pre-treatment HIV drug resistance and treatment failure in Nigerian children. AU - Boerma,Ragna S, AU - Boender,T Sonia, AU - Sigaloff,Kim C E, AU - Rinke de Wit,Tobias F, AU - van Hensbroek,Michael Boele, AU - Ndembi,Nicaise, AU - Adeyemo,Titilope, AU - Temiye,Edamisan O, AU - Osibogun,Akin, AU - Ondoa,Pascale, AU - Calis,Job C, AU - Akanmu,Alani Sulaimon, Y1 - 2016/11/10/ PY - 2016/04/19/received PY - 2016/09/09/revised PY - 2016/10/06/accepted PY - 2016/11/13/entrez PY - 2016/11/12/pubmed PY - 2017/9/21/medline KW - HIV drug resistance KW - HIV-1 KW - PMTCT KW - genotypic resistance testing KW - paediatric KW - sub-Saharan Africa SP - 21140 EP - 21140 JF - Journal of the International AIDS Society JO - J Int AIDS Soc VL - 19 IS - 1 N2 - INTRODUCTION: 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. METHODS: 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-based pol genotypic 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). RESULTS: 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). DISCUSSION: 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. CONCLUSIONS: 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. SN - 1758-2652 UR - https://www.unboundmedicine.com/medline/citation/27836020/High_levels_of_pre_treatment_HIV_drug_resistance_and_treatment_failure_in_Nigerian_children_ L2 - https://doi.org/10.7448/IAS.19.1.21140 DB - PRIME DP - Unbound Medicine ER -