Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are commonly used in pediatric patients; however, rapid development of resistance, due to non-adherence and cross-resistance, results in their discontinuation and limits their recycling. We evaluated the clinical experience of recycling NNRTIs despite documented NNRTI resistance (NNRTI-R), and examined virologic and CD4 cell count outcomes among participants enrolled in Longitudinal Epidemiologic Study to Gain Insight into HIV/AIDS in Children and Youth (LEGACY), a national HIV-infected pediatric cohort. We conducted a retrospective analysis of LEGACY participants with major NNRTI-R. Using chi-square analyses and logistic regression, we examined demographic and clinical factors associated with prescription of NNRTIs despite documented NNRTI-R, and associated changes in plasma HIV RNA viral load and CD4 cell counts. Sixteen of 133 (12%) participants with documented NNRTI-R re-started NNRTIs for a median of 370 days (IQR 105-919) with a median 402 days (IQR 70-841) between documentation of NNRTI-R to NNRTI recycling. Participants recycling NNRTIs were less likely to have documented past non-adherence (40.0% vs. 69.2%; p = 0.02). Among twelve patients with virologic data at 24 (+/- 8) weeks; seven (58.3%) experienced virologic suppression while on the recycled NNRTI-based regimens. Of the five who failed to suppress, three with subsequent genotyping developed additional NNRTI-R mutations compromising higher generation NNRTIs. While NNRTI's were recycled in only a small fraction of LEGACY participants harboring NNRTI-R mutations, such recycling increased the risk of inducing further resistance mutations that compromised use of higher generation NNRTIs.
Agwu, A. L., Chang, J. Y., Wiegand, R. E., Wheeling, J. T., Bohannon, B. A., & Dominguez, and the LEGACY Consortiu, K. L. (2014). Prevalence and Outcomes of Recycling NNRTIs Despite Documented NNRTI Resistance in HIV-Infected Children and Youth. AIDS Patient Care and STDs, 28(1), 10–14. https://doi.org/10.1089/apc.2013.0308