Phylogenetic evidence of HIV-1 sequence evolution in subjects with persistent low-level viraemia.

TitlePhylogenetic evidence of HIV-1 sequence evolution in subjects with persistent low-level viraemia.
Publication TypeJournal Article
Year of Publication2015
AuthorsVardhanabhuti S, Taiwo B, Kuritzkes DR, Eron JJ, Bosch RJ
JournalAntivir Ther
Volume20
Issue1
Pagination73-6
Date Published2015
ISSN2040-2058
KeywordsAdult, Anti-HIV Agents, Antiretroviral Therapy, Highly Active, Benzoxazines, Drug Resistance, Viral, Evolution, Molecular, Female, HIV Infections, HIV-1, Humans, Lopinavir, Male, Middle Aged, Mutation, Phylogeny, pol Gene Products, Human Immunodeficiency Virus, Retrospective Studies, Ritonavir, RNA, Viral, Viral Load, Viremia
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.

DOI10.3851/IMP2772
Alternate JournalAntivir. Ther. (Lond.)
PubMed ID24699164
PubMed Central IDPMC4185268
Grant ListAI-68634 / AI / NIAID NIH HHS / United States
AI-68636 / AI / NIAID NIH HHS / United States
AI50410 / AI / NIAID NIH HHS / United States
AI69423 / AI / NIAID NIH HHS / United States
P30 AI050410 / AI / NIAID NIH HHS / United States
P30 AI060354 / AI / NIAID NIH HHS / United States
RR025747 / RR / NCRR NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States
UM1 AI106701 / AI / NIAID NIH HHS / United States