Yifan Li
(U.S. Military HIV Research Program, CIDR, Walter Reed Army Institute of Research, Silver Spring, MD; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD)
About 25% of HIV-1 infections are initiated by multiple founder variants based on HIV-1 sequencing via single genome amplification (SGA). Infections with multiple HIV-1 variants are associated with poorer clinical outcomes. Compared to SGA, deep-sequencing platforms offer high resolution to study within-host genetic diversity. We investigated the genetic characteristics of HIV-1 populations during acute infection for persons living with HIV-1 (PLWH) enrolled in the RV254 acute HIV-1 infection cohort in Bangkok, Thailand.
Samples from 49 PLWH were collected at HIV-1 diagnosis in Fiebig stage I-V and the Pacific Biosciences single molecule real-time platform was used to sequence PCR amplicons derived from cDNA templates tagged with unique molecular identifiers (SMRT-UMI). Most participants (n=42) had Rev-Env-Nef sequences that corresponded to CRF01_AE (five subtype B/CRF01_AE recombinants, one subtype B, one G/CRF02_AG recombinant). After sequence quality control, an average of 542 Rev-Env-Nef sequences were derived per sample, with an average of 203 unique sequences per sample. Sequence diversity was low with an average mean pairwise diversity of 0.004 (min=0.0003 and max=0.05). The analysis of maximum pairwise diversity (0.018 (0.002, 0.175)) along with phylogenetic trees showed the presence of distant lineages corresponding to co-infections with two independent HIV-1 strains in five participants.
We identified multiple lineages (with ≥10 substitutions) in 19 participants. For these participants, the most frequent lineage corresponded to 87.67% of the population [56.07%-99.87%]. Rare lineages corresponding to <3% of the viral population were found in 12 out of 19 participants. In 10 of these 12 participants, these lineages were present only as singletons and all corresponded to functional Env.
Our results showed that multiple founder lineages were found in a higher fraction of infections (39%) than reported based on SGA sequencing, as expected with the PacBio SMRT-UMI strategy. This strategy allowed detection of rare lineages whose biological significance needs to be evaluated.
Yifan Li
(U.S. Military HIV Research Program, CIDR, Walter Reed Army Institute of Research, Silver Spring, MD; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD)
Phuc Pham
(U.S. Military HIV Research Program, CIDR, Walter Reed Army Institute of Research, Silver Spring, MD; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD)
Matthew Lind
(U.S. Military HIV Research Program, CIDR, Walter Reed Army Institute of Research, Silver Spring, MD; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD)
Phillip Kuri
(U.S. Military HIV Research Program, CIDR, Walter Reed Army Institute of Research, Silver Spring, MD; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD)
Eric Sanders-Buell
(U.S. Military HIV Research Program, CIDR, Walter Reed Army Institute of Research, Silver Spring, MD; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD)
Bethany Dearlove
(U.S. Military HIV Research Program, CIDR, Walter Reed Army Institute of Research, Silver Spring, MD; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD)
Eric Lewitus
(U.S. Military HIV Research Program, CIDR, Walter Reed Army Institute of Research, Silver Spring, MD; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD)
Dylan Westfall
(University of Washington, Seattle, WA)
James Mullins
(University of Washington, Seattle, WA)
Nicha Tulmethakaan
(SEARCH Research Foundation, Bangkok, Thailand)
Somchai Sriplienchan
(SEARCH Research Foundation, Bangkok, Thailand)
Eugène Kroon
(SEARCH Research Foundation, Bangkok, Thailand)
Nittaya Phanuphak
(Institute of HIV Research and Innovation, Bangkok, Thailand)
Carlo Sacdalan
(SEARCH Research Foundation, Bangkok, Thailand; Research Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand)
Julie Ake
(U.S. Military HIV Research Program, CIDR, Walter Reed Army Institute of Research, Silver Spring, MD)
Sandhya Vasan
(U.S. Military HIV Research Program, CIDR, Walter Reed Army Institute of Research, Silver Spring, MD; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD)
Merlin Robb
(U.S. Military HIV Research Program, CIDR, Walter Reed Army Institute of Research, Silver Spring, MD; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD)
Donn Colby
(U.S. Military HIV Research Program, CIDR, Walter Reed Army Institute of Research, Silver Spring, MD; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD)
Lydie Trautmann
(U.S. Military HIV Research Program, CIDR, Walter Reed Army Institute of Research, Silver Spring, MD; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD)
Morgane Rolland
(U.S. Military HIV Research Program, CIDR, Walter Reed Army Institute of Research, Silver Spring, MD; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD)
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