2507. Transmitted and Acquired NNRTI Resistance in the Philippines: Are Newer Generation NNRTIs a Viable Option?

Open Forum Infectious Diseases(2019)

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Abstract Background Doravirine, rilpivirine, and etravirine are newer generation non-nucleoside reverse transcriptase inhibitors (NNRTI) that are intended to be more durable alternatives to efavirenz and nevirapine. We examined transmitted drug resistance (TDR) and acquired drug resistance (ADR) to NNRTIs from recent local TDR and ADR data to determine whether these can be useful as first-line or second-line antiretroviral (ARV) agents. Methods We reanalyzed Sanger-Based sequences (SBS) from an ADR surveillance study; and SBS and near-whole-genome next-generation sequences (NGS) from a TDR surveillance study using the Stanford HIV Drug Resistance Database. Results ADR: Out of 513 Filipino PLHIV from an ADR surveillance study on one year of ARV treatment, 53 (10.3%) failed (HIV VL >1,000 copies/mL). Among these, 48 had clinically significant mutations. Table 1 shows NNRTI ADR frequencies. There was no significant ADR difference between first-generation and newer generation NNRTIs. TDR: 298 treatment-naïve Filipino PLHIV underwent baselines sequencing. All 298 had SBS. 266 had successful NGS. Table 1 shows SBS and NGS TDR NNRTI resistance at a 5% minor variant cutoff. There was no significant TDR difference between first-generation and newer generation NNRTIs. Conclusion ADR and TDR rates to the newer NNRTIs are similar to first-generation NNRTIs. High TDR to doravirine on NGS is concerning, but its clinical significance is unclear. Etravirine had the lowest TDR and ADR and may be the most useful new-generation NNRTI. However, integrase strand transfer inhibitor-based regimens will likely be more durable. Disclosures All authors: No reported disclosures.
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