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

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

doi:10.1093/infdis/jir651

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

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

School of Medicine

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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.

Original language	English (US)
Pages (from-to)	1918-1926
Number of pages	9
Journal	Journal of Infectious Diseases
Volume	204
Issue number	12
DOIs	https://doi.org/10.1093/infdis/jir651
State	Published - Dec 15 2011

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Medicine(all)

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Eshleman, S. H., Hudelson, S. E., Redd, A. D., Wang, L., Debes, R., Chen, Y. Q., Martens, C. A., Ricklefs, S. M., Selig, E. J., Porcella, S. F., Munshaw, S., Ray, S. C., Piwowar-Manning, E., McCauley, M., Hosseinipour, M. C., Kumwenda, J., Hakim, J. G., Chariyalertsak, S., De Bruyn, G., ... Hughes, J. P. (2011). Analysis of genetic linkage of HIV from couples enrolled in the HIV prevention trials network 052 trial. Journal of Infectious Diseases, 204(12), 1918-1926. https://doi.org/10.1093/infdis/jir651

Eshleman, SH, Hudelson, SE, Redd, AD, 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

@article{4fee95aa8afa4055b20f26edb8c50d12,

title = "Analysis of genetic linkage of HIV from couples enrolled in the HIV prevention trials network 052 trial",

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 = "Eshleman, {Susan H.} and Hudelson, {Sarah E.} and Redd, {Andrew D.} 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 C.} 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.}",

note = "Funding Information: Financial support. This work was supported by the HIV Prevention Trials Network (HPTN) sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), the National Institute on Drug Abuse (NIDA), the National Institute of Mental Health (NIMH), and the Office of AIDS Research, of NIH, Department of Health and Human Services (U01AI068613/UM1AI068613 to HPTN Network Laboratory; U01AI068617 to HPTN Statistical and Data Management Center; and U01AI068619 to HPTN Core and Operations Center); the Division of Intramural Research, NIAID, NIH; NIAID, NIH (R01AI029168); and NIDA, NIH (R01DA024565).",

year = "2011",

month = dec,

day = "15",

doi = "10.1093/infdis/jir651",

language = "English (US)",

volume = "204",

pages = "1918--1926",

journal = "Journal of Infectious Diseases",

issn = "0022-1899",

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number = "12",

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TY - JOUR

T1 - Analysis of genetic linkage of HIV from couples enrolled in the HIV prevention trials network 052 trial

AU - Eshleman, Susan H.

AU - Hudelson, Sarah E.

AU - Redd, Andrew D.

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 C.

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.

N1 - Funding Information: Financial support. This work was supported by the HIV Prevention Trials Network (HPTN) sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), the National Institute on Drug Abuse (NIDA), the National Institute of Mental Health (NIMH), and the Office of AIDS Research, of NIH, Department of Health and Human Services (U01AI068613/UM1AI068613 to HPTN Network Laboratory; U01AI068617 to HPTN Statistical and Data Management Center; and U01AI068619 to HPTN Core and Operations Center); the Division of Intramural Research, NIAID, NIH; NIAID, NIH (R01AI029168); and NIDA, NIH (R01DA024565).

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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DO - 10.1093/infdis/jir651

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SN - 0022-1899

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JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

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ER -

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

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