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J Infect Dis. 2018 Dec 24. doi: 10.1093/infdis/jiy734. [Epub ahead of print]

Phylogenetic methods inconsistently predict direction of HIV transmission among heterosexual pairs in the HPTN052 cohort.

Author information

1
BioInfoExperts, LLC, Thibodaux, LA, USA.
2
Big Data Institute, Oxford University, Oxford, UK.
3
Laboratory of Immunoregulation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Baltimore, MD, USA.
4
Genomics Unit, Research Technologies Section, Rocky Mountain Laboratories, Division of Intramural Research, NIAID, NIH, Hamilton, MT, USA.
5
Dept. of Pathology, Johns Hopkins Univ. School of Medicine, Baltimore, MD, USA.
6
Science Facilitation Department, FHI360, Durham, NC, USA.
7
Vaccine and Infectious Disease Science Division, Fred Hutchinson Cancer Research Institute, Seattle, WA, USA.
8
College of Medicine-Johns Hopkins Project, Blantyre, Malawi.
9
Dept. of Medicine, Univ. of North Carolina at Chapel Hill, Chapel Hill, NC.
10
University of Zimbabwe, Harare, Zimbabwe.
11
YRGCARE Medical Centre, Chennai, India.
12
Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand.
13
Hospital Geral de Nova IguaƧu and Laboratorio de AIDS e Imunologia Molecular (IOC/Fiocruz), Rio de Janeiro, Brazil.
14
Instituto Nacional de Infectologia Evandro Chagas-INI-Fiocruz, Rio de Janeiro, Brazil.
15
Centers for Disease Control and Prevention (CDC) Division of HIV/AIDS Prevention/KEMRI- CDC Research and Public Health Collaboration HIV Research Branch, Kisumu, Kenya.
16
Botswana Harvard AIDS Institute, Gabarone, Botswana.
17
Servico de Infectologia, Hospital Nossa Senhora da Conceicao/GHC, Porto Alegre, Brazil.

Abstract

Background:

We evaluated use of phylogenetic methods to predict the direction of HIV transmission.

Methods:

For 33 index-partner pairs with genetically-linked infection, samples were collected from partners and indexes close to time of partners' seroconversion (SC); 31 indexes also had an earlier sample. Phylogenies were inferred using env next-generation sequences (one tree per pair/subtype). Direction of transmission (DoT) predicted from each tree was classified as correct or incorrect based on which sequences (index or partner) were closest to the root. DoT was also assessed using maximum-parsimony to infer ancestral node states for 100 bootstrap trees.

Results:

DoT was predicted correctly for both single pair and subtype-specific trees in 22 pairs (67%) using SC samples and 23 pairs (74%) using early index samples. DoT was predicted incorrectly for four pairs (15%) using SC or early index samples. In the bootstrap analysis, DoT was predicted correctly for 18 pairs (55%) using SC samples and 24 pairs (73%) using early index samples. DoT was predicted incorrectly for seven pairs (21%) using SC samples and four pairs (13%) using early index samples.

Conclusions:

Phylogenetic methods based solely on tree topology of HIV env sequences, particularly without consideration of phylogenetic uncertainty, may be insufficient for determining DoT.

PMID:
30590741
DOI:
10.1093/infdis/jiy734

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