Drug resistance patterns following pharmacy stock shortage in Nigerian Antiretroviral Treatment Program

Seema T. Meloni, Beth Chaplin, John Idoko, Oche Agbaji, Sulaimon Akanmu, Godwin Imade, Prosper Okonkwo, Robert L. Murphy, Phyllis J. Kanki*

*Corresponding author for this work

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Background: For patients on antiretroviral therapy (ART), treatment interruptions can impact patient outcomes and result in the accumulation of drug resistance mutations leading to virologic failure. There are minimal published data on the impact of an ART stock shortage on development of drug resistance mutations (DRMs). In this report, we evaluate data from patients enrolled in the Government of Nigeria National ART Program that were receiving treatment at the time of a national drug shortage in late 2003. Methods: We conducted a cross-sectional evaluation of samples collected between December 2004 and August 2005 from ART patients in virologic failure that either had a treatment interruption or did not during the late 2003 drug shortage period at the Jos University Teaching Hospital (JUTH). Plasma virus was genotyped, sequence data were edited and analyzed, and mutation profiles were categorized to evaluate predicted drug susceptibility. Data were analyzed to examine factors associated with development of resistance mutations. A genotypic sensitivity score to the alternate recommended regimen was computed to assess drug susceptibility if regimens were changed. Results: A total of 56 patients were included in this evaluation (28 interrupted, 28 uninterrupted). Patients in the interrupted group had more DRMs than those in the uninterrupted group (p < 0.001); interrupted patients were more likely than uninterrupted patients to have one or more TAM-2 mutations (57.1% interrupted vs. 21.3% uninterrupted; p = 0.04). There was a statistically significant difference in resistance to both d4T (53.7% interrupted vs. 17.9 uninterrupted; p = 0.011) and AZT (64.3% interrupted vs. 25.0% uninterrupted; p = 0.003) by drug interruption status. Examining genotypic sensitivity scores, we found that 67.9% of the interrupted patients, as compared to 25.0% of the uninterrupted patients, did not have full susceptibility to one drug in the regimen to which guidelines recommended they be switched (p = 0.001). Discussion: In this small observational study, we found evidence of a difference in resistance profiles and ART susceptibility between those that were stocked-out of drug versus those that were not. We believe that these data are relevant for many other low- and middle-income countries (LMIC) that also experienced similar ART shortages as they rapidly scaled up their national programs.

Original languageEnglish (US)
Article number58
JournalAIDS Research and Therapy
Volume14
Issue number1
DOIs
StatePublished - Oct 13 2017

Keywords

  • Antiretroviral therapy
  • Drug resistance
  • Drug shortage
  • Mutations
  • Nigeria
  • Unstructured treatment interruption

ASJC Scopus subject areas

  • Molecular Medicine
  • Virology
  • Pharmacology (medical)

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    Meloni, S. T., Chaplin, B., Idoko, J., Agbaji, O., Akanmu, S., Imade, G., Okonkwo, P., Murphy, R. L., & Kanki, P. J. (2017). Drug resistance patterns following pharmacy stock shortage in Nigerian Antiretroviral Treatment Program. AIDS Research and Therapy, 14(1), [58]. https://doi.org/10.1186/s12981-017-0184-5