High levels of dual-class drug resistance in HIV-infected children failing first-line antiretroviral therapy in Southern Ethiopia

Birkneh Tilahun Tadesse, Natalie N. Kinloch, Bemuluyigza Baraki, Hope R. Lapointe, Kyle D. Cobarrubias, Mark A. Brockman, Chanson J. Brumme, Byron (Alex) Foster, Degu Jerene, Eyasu Makonnen, Eleni Aklillu, Zabrina L. Brumme

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Clinical monitoring of pediatric HIV treatment remains a major challenge in settings where drug resistance genotyping is not routinely available. As a result, our understanding of drug resistance, and its impact on subsequent therapeutic regimens available in these settings, remains limited. We investigate the prevalence and correlates of HIV-1 drug resistance among 94 participants of the Ethiopia Pediatric HIV Cohort failing first-line combination antiretroviral therapy (cART) using dried blood spot-based genotyping. Overall, 81% (73/90) of successfully genotyped participants harbored resistance mutations, including 69% (62/90) who harbored resistance to both Nucleoside Reverse Transcriptase Inhibitors (NRTIs) and Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs). Strikingly, 42% of resistant participants harbored resistance to all four NRTIs recommended for second-line use in this setting, meaning that there are effectively no remaining cART options for these children. Longer cART duration and prior regimen changes were significantly associated with detection of drug resistance mutations. Replicate genotyping increased the breadth of drug resistance detected in 34% of cases, and thus is recommended for consideration when typing from blood spots. Implementation of timely drug resistance testing and access to newer antiretrovirals and drug classes are urgently needed to guide clinical decision-making and improve outcomes for HIV-infected children on first-line cART in Ethiopia.

Original languageEnglish (US)
Article number60
JournalViruses
Volume10
Issue number2
DOIs
StatePublished - Feb 1 2018

Fingerprint

Ethiopia
Drug Resistance
HIV
Reverse Transcriptase Inhibitors
Nucleosides
Therapeutics
Blood Grouping and Crossmatching
Pediatrics
Mutation
HIV-1
Pharmaceutical Preparations

Keywords

  • Children
  • Dried blood spots
  • Drug resistance
  • Ethiopia
  • First-line combination antiretroviral therapy (cART)
  • Genotyping
  • HIV
  • Pediatrics
  • Treatment failure

ASJC Scopus subject areas

  • Infectious Diseases
  • Virology

Cite this

Tadesse, B. T., Kinloch, N. N., Baraki, B., Lapointe, H. R., Cobarrubias, K. D., Brockman, M. A., ... Brumme, Z. L. (2018). High levels of dual-class drug resistance in HIV-infected children failing first-line antiretroviral therapy in Southern Ethiopia. Viruses, 10(2), [60]. https://doi.org/10.3390/v10020060

High levels of dual-class drug resistance in HIV-infected children failing first-line antiretroviral therapy in Southern Ethiopia. / Tadesse, Birkneh Tilahun; Kinloch, Natalie N.; Baraki, Bemuluyigza; Lapointe, Hope R.; Cobarrubias, Kyle D.; Brockman, Mark A.; Brumme, Chanson J.; Foster, Byron (Alex); Jerene, Degu; Makonnen, Eyasu; Aklillu, Eleni; Brumme, Zabrina L.

In: Viruses, Vol. 10, No. 2, 60, 01.02.2018.

Research output: Contribution to journalArticle

Tadesse, BT, Kinloch, NN, Baraki, B, Lapointe, HR, Cobarrubias, KD, Brockman, MA, Brumme, CJ, Foster, BA, Jerene, D, Makonnen, E, Aklillu, E & Brumme, ZL 2018, 'High levels of dual-class drug resistance in HIV-infected children failing first-line antiretroviral therapy in Southern Ethiopia', Viruses, vol. 10, no. 2, 60. https://doi.org/10.3390/v10020060
Tadesse, Birkneh Tilahun ; Kinloch, Natalie N. ; Baraki, Bemuluyigza ; Lapointe, Hope R. ; Cobarrubias, Kyle D. ; Brockman, Mark A. ; Brumme, Chanson J. ; Foster, Byron (Alex) ; Jerene, Degu ; Makonnen, Eyasu ; Aklillu, Eleni ; Brumme, Zabrina L. / High levels of dual-class drug resistance in HIV-infected children failing first-line antiretroviral therapy in Southern Ethiopia. In: Viruses. 2018 ; Vol. 10, No. 2.
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