Analysis of genetic linkage of HIV from couples enrolled in the HIV prevention trials network 052 trial

Susan Eshleman, Sarah E. Hudelson, Andrew Redd, Lei Wang, Rachel Debes, Ying Q. Chen, Craig A. Martens, Stacy M. Ricklefs, Ethan J. Selig, Stephen F. Porcella, Supriya Munshaw, Stuart Campbell Ray, Estelle Piwowar-Manning, Marybeth McCauley, Mina C. Hosseinipour, Johnstone Kumwenda, James G. Hakim, Suwat Chariyalertsak, Guy De Bruyn, Beatriz Grinsztejn & 8 others Nagalingeswaran Kumarasamy, Joseph Makhema, Kenneth H. Mayer, Jose Pilotto, Breno R. Santos, Thomas C Quinn, Myron S. Cohen, James P. Hughes

Research output: Contribution to journalArticle

Abstract

Background. The HIV Prevention Trials Network (HPTN) 052 trial demonstrated that early initiation of antiretroviral therapy (ART) reduces human immunodeficiency virus (HIV) transmission from HIV-infected adults (index participants) to their HIV-uninfected sexual partners. We analyzed HIV from 38 index-partner pairs and 80 unrelated index participants (controls) to assess the linkage of seroconversion events. Methods. Linkage was assessed using phylogenetic analysis of HIV pol sequences and Bayesian analysis of genetic distances between pol sequences from index-partner pairs and controls. Selected samples were also analyzed using next-generation sequencing (env region). Results. In 29 of the 38 (76.3%) cases analyzed, the index was the likely source of the partner's HIV infection (linked). In 7 cases (18.4%), the partner was most likely infected from a source other than the index participant (unlinked). In 2 cases (5.3%), linkage status could not be definitively established. Conclusions. Nearly one-fifth of the seroconversion events in HPTN 052 were unlinked. The association of early ART and reduced HIV transmission was stronger when the analysis included only linked events. This underscores the importance of assessing the genetic linkage of HIV seroconversion events in HIV prevention studies involving serodiscordant couples.

Original languageEnglish (US)
Pages (from-to)1918-1926
Number of pages9
JournalJournal of Infectious Diseases
Volume204
Issue number12
DOIs
StatePublished - Dec 15 2011

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Genetic Linkage
HIV
Bayes Theorem
Sexual Partners
Virus Diseases
Secondary Prevention
Sequence Analysis

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy

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Analysis of genetic linkage of HIV from couples enrolled in the HIV prevention trials network 052 trial. / Eshleman, Susan; Hudelson, Sarah E.; Redd, Andrew; Wang, Lei; Debes, Rachel; Chen, Ying Q.; Martens, Craig A.; Ricklefs, Stacy M.; Selig, Ethan J.; Porcella, Stephen F.; Munshaw, Supriya; Ray, Stuart Campbell; Piwowar-Manning, Estelle; McCauley, Marybeth; Hosseinipour, Mina C.; Kumwenda, Johnstone; Hakim, James G.; Chariyalertsak, Suwat; De Bruyn, Guy; Grinsztejn, Beatriz; Kumarasamy, Nagalingeswaran; Makhema, Joseph; Mayer, Kenneth H.; Pilotto, Jose; Santos, Breno R.; Quinn, Thomas C; Cohen, Myron S.; Hughes, James P.

In: Journal of Infectious Diseases, Vol. 204, No. 12, 15.12.2011, p. 1918-1926.

Research output: Contribution to journalArticle

Eshleman, S, Hudelson, SE, Redd, A, Wang, L, Debes, R, Chen, YQ, Martens, CA, Ricklefs, SM, Selig, EJ, Porcella, SF, Munshaw, S, Ray, SC, Piwowar-Manning, E, McCauley, M, Hosseinipour, MC, Kumwenda, J, Hakim, JG, Chariyalertsak, S, De Bruyn, G, Grinsztejn, B, Kumarasamy, N, Makhema, J, Mayer, KH, Pilotto, J, Santos, BR, Quinn, TC, Cohen, MS & Hughes, JP 2011, 'Analysis of genetic linkage of HIV from couples enrolled in the HIV prevention trials network 052 trial', Journal of Infectious Diseases, vol. 204, no. 12, pp. 1918-1926. https://doi.org/10.1093/infdis/jir651
Eshleman, Susan ; Hudelson, Sarah E. ; Redd, Andrew ; Wang, Lei ; Debes, Rachel ; Chen, Ying Q. ; Martens, Craig A. ; Ricklefs, Stacy M. ; Selig, Ethan J. ; Porcella, Stephen F. ; Munshaw, Supriya ; Ray, Stuart Campbell ; Piwowar-Manning, Estelle ; McCauley, Marybeth ; Hosseinipour, Mina C. ; Kumwenda, Johnstone ; Hakim, James G. ; Chariyalertsak, Suwat ; De Bruyn, Guy ; Grinsztejn, Beatriz ; Kumarasamy, Nagalingeswaran ; Makhema, Joseph ; Mayer, Kenneth H. ; Pilotto, Jose ; Santos, Breno R. ; Quinn, Thomas C ; Cohen, Myron S. ; Hughes, James P. / Analysis of genetic linkage of HIV from couples enrolled in the HIV prevention trials network 052 trial. In: Journal of Infectious Diseases. 2011 ; Vol. 204, No. 12. pp. 1918-1926.
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abstract = "Background. The HIV Prevention Trials Network (HPTN) 052 trial demonstrated that early initiation of antiretroviral therapy (ART) reduces human immunodeficiency virus (HIV) transmission from HIV-infected adults (index participants) to their HIV-uninfected sexual partners. We analyzed HIV from 38 index-partner pairs and 80 unrelated index participants (controls) to assess the linkage of seroconversion events. Methods. Linkage was assessed using phylogenetic analysis of HIV pol sequences and Bayesian analysis of genetic distances between pol sequences from index-partner pairs and controls. Selected samples were also analyzed using next-generation sequencing (env region). Results. In 29 of the 38 (76.3{\%}) cases analyzed, the index was the likely source of the partner's HIV infection (linked). In 7 cases (18.4{\%}), the partner was most likely infected from a source other than the index participant (unlinked). In 2 cases (5.3{\%}), linkage status could not be definitively established. Conclusions. Nearly one-fifth of the seroconversion events in HPTN 052 were unlinked. The association of early ART and reduced HIV transmission was stronger when the analysis included only linked events. This underscores the importance of assessing the genetic linkage of HIV seroconversion events in HIV prevention studies involving serodiscordant couples.",
author = "Susan Eshleman and Hudelson, {Sarah E.} and Andrew Redd and Lei Wang and Rachel Debes and Chen, {Ying Q.} and Martens, {Craig A.} and Ricklefs, {Stacy M.} and Selig, {Ethan J.} and Porcella, {Stephen F.} and Supriya Munshaw and Ray, {Stuart Campbell} and Estelle Piwowar-Manning and Marybeth McCauley and Hosseinipour, {Mina C.} and Johnstone Kumwenda and Hakim, {James G.} and Suwat Chariyalertsak and {De Bruyn}, Guy and Beatriz Grinsztejn and Nagalingeswaran Kumarasamy and Joseph Makhema and Mayer, {Kenneth H.} and Jose Pilotto and Santos, {Breno R.} and Quinn, {Thomas C} and Cohen, {Myron S.} and Hughes, {James P.}",
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AU - Eshleman, Susan

AU - Hudelson, Sarah E.

AU - Redd, Andrew

AU - Wang, Lei

AU - Debes, Rachel

AU - Chen, Ying Q.

AU - Martens, Craig A.

AU - Ricklefs, Stacy M.

AU - Selig, Ethan J.

AU - Porcella, Stephen F.

AU - Munshaw, Supriya

AU - Ray, Stuart Campbell

AU - Piwowar-Manning, Estelle

AU - McCauley, Marybeth

AU - Hosseinipour, Mina C.

AU - Kumwenda, Johnstone

AU - Hakim, James G.

AU - Chariyalertsak, Suwat

AU - De Bruyn, Guy

AU - Grinsztejn, Beatriz

AU - Kumarasamy, Nagalingeswaran

AU - Makhema, Joseph

AU - Mayer, Kenneth H.

AU - Pilotto, Jose

AU - Santos, Breno R.

AU - Quinn, Thomas C

AU - Cohen, Myron S.

AU - Hughes, James P.

PY - 2011/12/15

Y1 - 2011/12/15

N2 - Background. The HIV Prevention Trials Network (HPTN) 052 trial demonstrated that early initiation of antiretroviral therapy (ART) reduces human immunodeficiency virus (HIV) transmission from HIV-infected adults (index participants) to their HIV-uninfected sexual partners. We analyzed HIV from 38 index-partner pairs and 80 unrelated index participants (controls) to assess the linkage of seroconversion events. Methods. Linkage was assessed using phylogenetic analysis of HIV pol sequences and Bayesian analysis of genetic distances between pol sequences from index-partner pairs and controls. Selected samples were also analyzed using next-generation sequencing (env region). Results. In 29 of the 38 (76.3%) cases analyzed, the index was the likely source of the partner's HIV infection (linked). In 7 cases (18.4%), the partner was most likely infected from a source other than the index participant (unlinked). In 2 cases (5.3%), linkage status could not be definitively established. Conclusions. Nearly one-fifth of the seroconversion events in HPTN 052 were unlinked. The association of early ART and reduced HIV transmission was stronger when the analysis included only linked events. This underscores the importance of assessing the genetic linkage of HIV seroconversion events in HIV prevention studies involving serodiscordant couples.

AB - Background. The HIV Prevention Trials Network (HPTN) 052 trial demonstrated that early initiation of antiretroviral therapy (ART) reduces human immunodeficiency virus (HIV) transmission from HIV-infected adults (index participants) to their HIV-uninfected sexual partners. We analyzed HIV from 38 index-partner pairs and 80 unrelated index participants (controls) to assess the linkage of seroconversion events. Methods. Linkage was assessed using phylogenetic analysis of HIV pol sequences and Bayesian analysis of genetic distances between pol sequences from index-partner pairs and controls. Selected samples were also analyzed using next-generation sequencing (env region). Results. In 29 of the 38 (76.3%) cases analyzed, the index was the likely source of the partner's HIV infection (linked). In 7 cases (18.4%), the partner was most likely infected from a source other than the index participant (unlinked). In 2 cases (5.3%), linkage status could not be definitively established. Conclusions. Nearly one-fifth of the seroconversion events in HPTN 052 were unlinked. The association of early ART and reduced HIV transmission was stronger when the analysis included only linked events. This underscores the importance of assessing the genetic linkage of HIV seroconversion events in HIV prevention studies involving serodiscordant couples.

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