Michael R Jordan1, Martina Penazzato2, Amandine Cournil3, Adolfo Vubil4, Ilesh Jani4, Gillian Hunt5, Sergio Carmona6, Gugu Maphalala7, Nobuhle Mthethwa7, Christine Watera8, Pontiano Kaleebu8, Christine Chakanyuka Musanhu9, Sekesai Mtapuri-Zinyowera10, Janet Dzangare11, Martine Peeters3, Chunfu Yang12, Neil Parkin13, Silvia Bertagnolio2. 1. Tufts University School of Medicine and Tufts Medical Center, Boston, Massachusetts. 2. Department of HIV/AIDS, World Health Organization, Geneva, Switzerland. 3. IRD UMI 233, INSERM U1175, Université de Montpellier, Unité TransVIHMI, France. 4. Instituto Nacional de Saúde, Maputo, Mozambique. 5. National Institute for Communicable Diseases. 6. Witwatersrand University, Johannesburg, South Africa. 7. Ministry of Health Swaziland, Mbabane. 8. Uganda Virus Research Institute, Entebbe. 9. World Health Organization, Country Office. 10. National Microbiology Reference Laboratory. 11. Ministry of Health and Child Care, Harare, Zimbabwe. 12. Division of Global HIV and TB, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia. 13. Data First Consulting, Belmont, California.
Abstract
BACKGROUND: Programs for the prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV) have been scaled up in many low- and middle-income countries. However, HIV drug resistance (HIVDR) data among HIV-1-infected young children remain limited. METHODS: Surveys of pretreatment HIVDR among children aged <18 months who were diagnosed with HIV through early infant diagnosis were conducted in 5 sub-Saharan African countries (Mozambique, Swaziland, South Africa, Uganda, and Zimbabwe) between 2011 and 2014 following World Health Organization (WHO) guidance. Deidentified demographic and clinical data were used to explore risk factors associated with nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance. RESULTS: Among the 1450 genotypes analyzed, 1048 had accompanying demographic and clinical data. The median age of children was 4 months; 50.4% were female. HIV from 54.1% showed resistance to 1 or more antiretroviral (ARV) drugs, with 53.0% and 8.8% having resistance to 1 or more NNRTI or nucleoside reverse transcriptase inhibitors, respectively. NNRTI resistance was particularly high in children exposed to ARV drugs through PMTCT; adjusted odds ratios were 1.8 (95% confidence interval [CI], 1.3-2.6) for maternal exposure only and 2.4 (CI, 1.6-3.6) for neonatal exposure only. CONCLUSIONS: Protease inhibitor-based regimens in children aged <3 years are currently recommended by WHO, but the implementation of this recommendation is suboptimal. These results reinforce the urgent need to overcome barriers to scaling up pediatric protease inhibitor-based regimens in sub-Saharan Africa and underscore the need to accelerate the study and approval of integrase inhibitors for use in young children.
BACKGROUND: Programs for the prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV) have been scaled up in many low- and middle-income countries. However, HIV drug resistance (HIVDR) data among HIV-1-infected young children remain limited. METHODS: Surveys of pretreatment HIVDR among children aged <18 months who were diagnosed with HIV through early infant diagnosis were conducted in 5 sub-Saharan African countries (Mozambique, Swaziland, South Africa, Uganda, and Zimbabwe) between 2011 and 2014 following World Health Organization (WHO) guidance. Deidentified demographic and clinical data were used to explore risk factors associated with nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance. RESULTS: Among the 1450 genotypes analyzed, 1048 had accompanying demographic and clinical data. The median age of children was 4 months; 50.4% were female. HIV from 54.1% showed resistance to 1 or more antiretroviral (ARV) drugs, with 53.0% and 8.8% having resistance to 1 or more NNRTI or nucleoside reverse transcriptase inhibitors, respectively. NNRTI resistance was particularly high in children exposed to ARV drugs through PMTCT; adjusted odds ratios were 1.8 (95% confidence interval [CI], 1.3-2.6) for maternal exposure only and 2.4 (CI, 1.6-3.6) for neonatal exposure only. CONCLUSIONS: Protease inhibitor-based regimens in children aged <3 years are currently recommended by WHO, but the implementation of this recommendation is suboptimal. These results reinforce the urgent need to overcome barriers to scaling up pediatric protease inhibitor-based regimens in sub-Saharan Africa and underscore the need to accelerate the study and approval of integrase inhibitors for use in young children.
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Authors: V Carnimeo; I A Pulido Tarquino; S Fuentes; D Vaz; L Molfino; N Tamayo Antabak; R M Cuco; A Couto; S Lobo; J de Amaral Fidelis; J S Mulassua; I Ciglenecki; T Ellman; B Schramm Journal: JAC Antimicrob Resist Date: 2021-05-12