Phylogenetic Evidence of HIV-1 Sequence Evolution in Subjects with Persistent Low-Level Viraemia

Abstract

Background

Persistent low-level viraemia (LLV) during the treatment of antiretroviral therapy (ART) is associated with emergent drug resistance mutation (DRM); however, insight into its driver is limited. The objectives were to study HIV-1 pol sequence evolution in subjects with persistent LLV and evaluate factors associated with sequence changes.

Methods

HIV-1 pol sequences from 54 treatment-naive subjects undergoing first-line lopinavir/ritonavir- or efavirenz-containing ART were obtained at pre-ART and end of LLV. HIV-1 sequence evolution was evaluated using phylogenetic analysis and Hamming distance calculation. DRMs were interpreted based on the International AIDS Society-USA 2011 update.

Results

Subjects with new DRM during LLV had greater HIV-1 evolution across pol from the pre-ART to end of LLV compared with subjects without DRM. Evolution over non-DRM sites was similar between groups. Higher degree of genetic evolution was positively associated with higher HIV-1 RNA levels during LLV, both at DRM and non-DRM sites.

Conclusions

The magnitude of LLV was the primary driver of evolution rate at DRM as well as non-DRM sites. Higher viral load was associated with DRM emergence in these subjects. These findings provide insights that may be applicable to the management of patients with persistent LLV during ART.