Work

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

Year: 2014

Type: article

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.

Source: Antiviral Therapy

DOI: 10.3851/imp2772

Authors: Saran Vardhanabhuti, Babafemi Taiwo, Daniel R Kuritzkes, Joseph J Eron, Ronald J Bosch

Institutions: Harvard University, Northwestern University, University of North Carolina at Chapel Hill

Language: English

Topic: HIV/AIDS drug development and treatment

Subfield: Infectious Diseases

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green