High Levels of Dual-Class Drug Resistance in HIV-Infected Children Failing First-Line Antiretroviral Therapy in Southern Ethiopia

Viruses. 2018 Feb 1;10(2):60. doi: 10.3390/v10020060.

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.

Keywords: Ethiopia; HIV; children; dried blood spots; drug resistance; first-line combination antiretroviral therapy (cART); genotyping; pediatrics; treatment failure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Anti-HIV Agents / pharmacology
  • Anti-HIV Agents / therapeutic use
  • Antiretroviral Therapy, Highly Active
  • CD4 Lymphocyte Count
  • Child
  • Drug Resistance, Viral*
  • Ethiopia / epidemiology
  • Female
  • Genotype
  • HIV Infections / drug therapy
  • HIV Infections / epidemiology*
  • HIV Infections / virology*
  • HIV-1 / drug effects*
  • HIV-1 / genetics
  • Humans
  • Male
  • Prevalence
  • RNA, Viral
  • Treatment Failure
  • Viral Load

Substances

  • Anti-HIV Agents
  • RNA, Viral