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
