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 language | English (US) |
|---|---|
| Article number | 60 |
| Journal | Viruses |
| Volume | 10 |
| Issue number | 2 |
| DOIs | |
| State | Published - Feb 1 2018 |
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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
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 journal › Article
}
TY - JOUR
T1 - High levels of dual-class drug resistance in HIV-infected children failing first-line antiretroviral therapy in Southern Ethiopia
AU - Tadesse, Birkneh Tilahun
AU - Kinloch, Natalie N.
AU - Baraki, Bemuluyigza
AU - Lapointe, Hope R.
AU - Cobarrubias, Kyle D.
AU - Brockman, Mark A.
AU - Brumme, Chanson J.
AU - Foster, Byron (Alex)
AU - Jerene, Degu
AU - Makonnen, Eyasu
AU - Aklillu, Eleni
AU - Brumme, Zabrina L.
PY - 2018/2/1
Y1 - 2018/2/1
N2 - 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.
AB - 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.
KW - Children
KW - Dried blood spots
KW - Drug resistance
KW - Ethiopia
KW - First-line combination antiretroviral therapy (cART)
KW - Genotyping
KW - HIV
KW - Pediatrics
KW - Treatment failure
UR - http://www.scopus.com/inward/record.url?scp=85041418802&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85041418802&partnerID=8YFLogxK
U2 - 10.3390/v10020060
DO - 10.3390/v10020060
M3 - Article
C2 - 29389912
AN - SCOPUS:85041418802
VL - 10
JO - Viruses
JF - Viruses
SN - 1999-4915
IS - 2
M1 - 60
ER -