Phylogenetic Methods Inconsistently Predict the Direction of HIV Transmission Among Heterosexual Pairs in the HPTN 052 Cohort

Rebecca Rose, Matthew Hall, Andrew D. Redd, Susanna Lamers, Andrew E. Barbier, Stephen F. Porcella, Sarah E. Hudelson, Estelle Piwowar-Manning, Marybeth McCauley, Theresa Gamble, Ethan A. Wilson, Johnstone Kumwenda, Mina C. Hosseinipour, James G. Hakim, Nagalingeswaran Kumarasamy, Suwat Chariyalertsak, Jose H. Pilotto, Beatriz Grinsztejn, Lisa A. Mills, Joseph MakhemaBreno R. Santos, Ying Q. Chen, Thomas C. Quinn, Christophe Fraser, Myron S. Cohen, Susan H. Eshleman, Oliver Laeyendecker

Research output: Contribution to journalArticle

Abstract

BACKGROUND: We evaluated use of phylogenetic methods to predict the direction of human immunodeficiency virus (HIV) transmission. METHODS: For 33 pairs of HIV-infected patients (hereafter, "index patients") and their partners who acquired genetically linked HIV infection during the study, samples were collected from partners and index patients close to the time when the partner seroconverted (hereafter, "SC samples"); for 31 pairs, samples collected from the index patient at an earlier time point (hereafter, "early index samples") were also available. Phylogenies were inferred using env next-generation sequences (1 tree per pair/subtype). The direction of transmission (DoT) predicted from each tree was classified as correct or incorrect on the basis of which sequences (those from the index patient or the 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%) by using SC samples and in 23 pairs (74%) by using early index samples. DoT was predicted incorrectly for 4 pairs (15%) by using SC or early index samples. In the bootstrap analysis, DoT was predicted correctly for 18 pairs (55%) by using SC samples and for 24 pairs (73%) by using early index samples. DoT was predicted incorrectly for 7 pairs (21%) by using SC samples and for 4 pairs (13%) by using early index samples. CONCLUSIONS: Phylogenetic methods based solely on the tree topology of HIV env sequences, particularly without consideration of phylogenetic uncertainty, may be insufficient for determining DoT.

Original languageEnglish (US)
Pages (from-to)1406-1413
Number of pages8
JournalThe Journal of infectious diseases
Volume220
Issue number9
DOIs
StatePublished - Sep 26 2019

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Heterosexuality
HIV
Direction compound
Virus Diseases
Phylogeny
Uncertainty

Keywords

  • epidemiology
  • Networks
  • viral dynamics

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

Cite this

Phylogenetic Methods Inconsistently Predict the Direction of HIV Transmission Among Heterosexual Pairs in the HPTN 052 Cohort. / Rose, Rebecca; Hall, Matthew; Redd, Andrew D.; Lamers, Susanna; Barbier, Andrew E.; Porcella, Stephen F.; Hudelson, Sarah E.; Piwowar-Manning, Estelle; McCauley, Marybeth; Gamble, Theresa; Wilson, Ethan A.; Kumwenda, Johnstone; Hosseinipour, Mina C.; Hakim, James G.; Kumarasamy, Nagalingeswaran; Chariyalertsak, Suwat; Pilotto, Jose H.; Grinsztejn, Beatriz; Mills, Lisa A.; Makhema, Joseph; Santos, Breno R.; Chen, Ying Q.; Quinn, Thomas C.; Fraser, Christophe; Cohen, Myron S.; Eshleman, Susan H.; Laeyendecker, Oliver.

In: The Journal of infectious diseases, Vol. 220, No. 9, 26.09.2019, p. 1406-1413.

Research output: Contribution to journalArticle

Rose, R, Hall, M, Redd, AD, Lamers, S, Barbier, AE, Porcella, SF, Hudelson, SE, Piwowar-Manning, E, McCauley, M, Gamble, T, Wilson, EA, Kumwenda, J, Hosseinipour, MC, Hakim, JG, Kumarasamy, N, Chariyalertsak, S, Pilotto, JH, Grinsztejn, B, Mills, LA, Makhema, J, Santos, BR, Chen, YQ, Quinn, TC, Fraser, C, Cohen, MS, Eshleman, SH & Laeyendecker, O 2019, 'Phylogenetic Methods Inconsistently Predict the Direction of HIV Transmission Among Heterosexual Pairs in the HPTN 052 Cohort', The Journal of infectious diseases, vol. 220, no. 9, pp. 1406-1413. https://doi.org/10.1093/infdis/jiy734
Rose, Rebecca ; Hall, Matthew ; Redd, Andrew D. ; Lamers, Susanna ; Barbier, Andrew E. ; Porcella, Stephen F. ; Hudelson, Sarah E. ; Piwowar-Manning, Estelle ; McCauley, Marybeth ; Gamble, Theresa ; Wilson, Ethan A. ; Kumwenda, Johnstone ; Hosseinipour, Mina C. ; Hakim, James G. ; Kumarasamy, Nagalingeswaran ; Chariyalertsak, Suwat ; Pilotto, Jose H. ; Grinsztejn, Beatriz ; Mills, Lisa A. ; Makhema, Joseph ; Santos, Breno R. ; Chen, Ying Q. ; Quinn, Thomas C. ; Fraser, Christophe ; Cohen, Myron S. ; Eshleman, Susan H. ; Laeyendecker, Oliver. / Phylogenetic Methods Inconsistently Predict the Direction of HIV Transmission Among Heterosexual Pairs in the HPTN 052 Cohort. In: The Journal of infectious diseases. 2019 ; Vol. 220, No. 9. pp. 1406-1413.
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T1 - Phylogenetic Methods Inconsistently Predict the Direction of HIV Transmission Among Heterosexual Pairs in the HPTN 052 Cohort

AU - Rose, Rebecca

AU - Hall, Matthew

AU - Redd, Andrew D.

AU - Lamers, Susanna

AU - Barbier, Andrew E.

AU - Porcella, Stephen F.

AU - Hudelson, Sarah E.

AU - Piwowar-Manning, Estelle

AU - McCauley, Marybeth

AU - Gamble, Theresa

AU - Wilson, Ethan A.

AU - Kumwenda, Johnstone

AU - Hosseinipour, Mina C.

AU - Hakim, James G.

AU - Kumarasamy, Nagalingeswaran

AU - Chariyalertsak, Suwat

AU - Pilotto, Jose H.

AU - Grinsztejn, Beatriz

AU - Mills, Lisa A.

AU - Makhema, Joseph

AU - Santos, Breno R.

AU - Chen, Ying Q.

AU - Quinn, Thomas C.

AU - Fraser, Christophe

AU - Cohen, Myron S.

AU - Eshleman, Susan H.

AU - Laeyendecker, Oliver

PY - 2019/9/26

Y1 - 2019/9/26

N2 - BACKGROUND: We evaluated use of phylogenetic methods to predict the direction of human immunodeficiency virus (HIV) transmission. METHODS: For 33 pairs of HIV-infected patients (hereafter, "index patients") and their partners who acquired genetically linked HIV infection during the study, samples were collected from partners and index patients close to the time when the partner seroconverted (hereafter, "SC samples"); for 31 pairs, samples collected from the index patient at an earlier time point (hereafter, "early index samples") were also available. Phylogenies were inferred using env next-generation sequences (1 tree per pair/subtype). The direction of transmission (DoT) predicted from each tree was classified as correct or incorrect on the basis of which sequences (those from the index patient or the 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%) by using SC samples and in 23 pairs (74%) by using early index samples. DoT was predicted incorrectly for 4 pairs (15%) by using SC or early index samples. In the bootstrap analysis, DoT was predicted correctly for 18 pairs (55%) by using SC samples and for 24 pairs (73%) by using early index samples. DoT was predicted incorrectly for 7 pairs (21%) by using SC samples and for 4 pairs (13%) by using early index samples. CONCLUSIONS: Phylogenetic methods based solely on the tree topology of HIV env sequences, particularly without consideration of phylogenetic uncertainty, may be insufficient for determining DoT.

AB - BACKGROUND: We evaluated use of phylogenetic methods to predict the direction of human immunodeficiency virus (HIV) transmission. METHODS: For 33 pairs of HIV-infected patients (hereafter, "index patients") and their partners who acquired genetically linked HIV infection during the study, samples were collected from partners and index patients close to the time when the partner seroconverted (hereafter, "SC samples"); for 31 pairs, samples collected from the index patient at an earlier time point (hereafter, "early index samples") were also available. Phylogenies were inferred using env next-generation sequences (1 tree per pair/subtype). The direction of transmission (DoT) predicted from each tree was classified as correct or incorrect on the basis of which sequences (those from the index patient or the 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%) by using SC samples and in 23 pairs (74%) by using early index samples. DoT was predicted incorrectly for 4 pairs (15%) by using SC or early index samples. In the bootstrap analysis, DoT was predicted correctly for 18 pairs (55%) by using SC samples and for 24 pairs (73%) by using early index samples. DoT was predicted incorrectly for 7 pairs (21%) by using SC samples and for 4 pairs (13%) by using early index samples. CONCLUSIONS: Phylogenetic methods based solely on the tree topology of HIV env sequences, particularly without consideration of phylogenetic uncertainty, may be insufficient for determining DoT.

KW - epidemiology

KW - Networks

KW - viral dynamics

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DO - 10.1093/infdis/jiy734

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