Limited Impact of First-Line Drug Resistance Mutations on Virologic Response Among Patients Receiving Second-Line Antiretroviral Therapy in Rural Uganda.

Abstract

Delayed detection of ART failure in settings without access to viral load (VL) monitoring has been hypothesized to lead to suboptimal response to second-line therapy due to accumulated drug resistance mutations (DRMs). We tested this hypothesis in a program setting in rural Uganda. From June 2012 to January 2014, we enrolled participants receiving nonnucleoside reverse transcriptase inhibitor-based first-line ART for ≥4 years, without access to VL monitoring. Participants who had a measured VL ≥ 1000 copies/mL on two occasions were switched to protease inhibitor-based regimens and followed every 6 months until September 2016. We measured VL at study exit. We conducted DRM testing at enrollment and study exit and examined factors associated with virologic failure. We enrolled 137 participants (64.3% female) with a median age of 44 years and a median duration on ART of 6.0 years. In a median of 2.8 years of follow-up, 7 (5%) died, 5 (3.6%) voluntarily withdrew, and 9 (6.6%) became lost to follow-up. Of 116 participants with a VL result at study exit, 20 (17%) had VL > 1000 copies/mL. Virologic failure was associated with reporting suboptimal adherence ( P = 0.028). Of patients with DRM data at enrollment, 103 of 105 (98%) had at least 1 DRM. Participants with thymidine analog mutations at enrollment were less likely to have virologic failure at study exit (11% vs. 36%; P = 0.007). No other DRMs were associated with failure. Even in the presence of multiple DRMs on first-line therapy, virologic failure after 3 years of protease inhibitor-based ART was infrequent. Suboptimal adherence to ART was associated with virologic failure.