Compartmentalized cytomegalovirus replication and transmission in the setting of maternal HIV-1 infection.

J Slyker; C Farquhar; C Atkinson; K Asbjörnsdóttir; A Roxby; A Drake; J Kiarie; A Wald; M Boeckh; B Richardson; K Odem-Davis; G John-Stewart; V Emery

doi:10.1093/cid/cit727

Compartmentalized cytomegalovirus replication and transmission in the setting of maternal HIV-1 infection.

J Slyker, C Farquhar, C Atkinson, K Asbjörnsdóttir, A Roxby, A Drake, J Kiarie, A Wald, M Boeckh, B Richardson, K Odem-Davis, G John-Stewart, V Emery

Faculty of Medicine

Research output: Contribution to journal › Article › peer-review

Abstract

Background. Cytomegalovirus (CMV) infection is associated with adverse outcomes in human immunodeficiency virus (HIV)-exposed infants. Determinants of vertical CMV transmission in the setting of maternal HIV-1 infection are not well-defined.Methods. CMV and HIV-1 levels were measured in plasma, cervical secretions, and breast milk of 147 HIV-1-infected women to define correlates of maternal CMV replication and infant CMV acquisition.Results. Although few women had detectable CMV in plasma (4.8%), the majority had detectable CMV DNA in cervical secretions (66%) and breast milk (99%). There was a strong association between cervical CMV detection during pregnancy and later breast milk levels (= 0.47; P =. 005). Plasma HIV-1 level and CD4 counts were associated with CMV in the cervix and breast milk. However HIV-1 levels within the cervix and breast milk were not associated with CMV within these compartments. Maternal breast milk CMV levels (hazard ratio [HR], 1.4; P =. 003) and maternal CD4 < 450 cells/mm³ (HR, 1.8; P =. 008) were independently associated with infant CMV acquisition; each log₁₀ increase in breast milk CMV was associated with a 40% increase in infant infection. The breast milk CMV level required to attain a 50% probability of CMV transmission increased with higher maternal CD4 counts, increasing from 3.55 log₁₀ CMV DNA copies/mL at a CD4 count of 350 cells/mm³ to 5.50 log₁₀ CMV DNA copies/mL at a CD4 count of 1000 cells/mm³.Conclusions. Breast milk CMV levels and maternal CD4 count are major determinants of CMV transmission in the setting of maternal HIV-1. Maternal immune reconstitution or lowering breast milk CMV levels may reduce vertical CMV transmission.

Original language	English
Pages (from-to)	564-572
Number of pages	9
Journal	Clinical Infectious Diseases
Volume	58
Issue number	4
DOIs	https://doi.org/10.1093/cid/cit727
Publication status	Published - Nov 2013

Bibliographical note

Funding Information:
Financial support. This study was supported by K01AI087369 (J. S.) from the National Institute of Allergy and Infectious Diseases (NIAID), and by an Emerging Opportunity Grant (J. S.) from the University of Washington Center for AIDS Research (CFAR), a National Institutes of Health (NIH)–funded program (P30 AI027757), which is supported by the following NIH Institutes and Centers: NIAID, National Cancer Institute, National Institute of Mental Health, National Institute on Drug Abuse, National Institute of Child Health and Human Development, NIH Heart, Lung, and Blood Institute, and the National Institute on Aging. A. D. was supported by a CFAR Training Grant (T32 AI07140-32), and A. R. was a scholar in the International AIDS Research and Training Program, funded by the Fogarty International Center, NIH (D43 TW000007) and was a Fogarty International Clinical Research Fellow (R24 TW007988). V. C. E. is supported through the MRC Centre for Clinical Virology. The randomized trial was conducted with the support of US NIH research grants (R03 HD 057773, R03 HD 057773-02S1, R01 AI076105; K24 AI087399 to C. F.; K24 HD 054314 to G. J. S.; K24 AI071113 and PO1 AI30731 to A. W.; K24 HL093294 to M. B.); a Puget Sound Partners for Global Health Research and Technology Grant; and a University of Washington Royalty Research Fund Grant (to C. F.). GlaxoSmithKline donated study drug and matched placebo but had no role in the study.

Other keywords

compartmentalization
cytomegalovirus
human immunodeficiency virus
neonates
opportunistic infection

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Slyker, J., Farquhar, C., Atkinson, C., Asbjörnsdóttir, K., Roxby, A., Drake, A., Kiarie, J., Wald, A., Boeckh, M., Richardson, B., Odem-Davis, K., John-Stewart, G., & Emery, V. (2013). Compartmentalized cytomegalovirus replication and transmission in the setting of maternal HIV-1 infection. Clinical Infectious Diseases, 58(4), 564-572. https://doi.org/10.1093/cid/cit727

@article{09745714605f4815a23c229c0ecd66e2,

title = "Compartmentalized cytomegalovirus replication and transmission in the setting of maternal HIV-1 infection.",

abstract = "Background. Cytomegalovirus (CMV) infection is associated with adverse outcomes in human immunodeficiency virus (HIV)-exposed infants. Determinants of vertical CMV transmission in the setting of maternal HIV-1 infection are not well-defined.Methods. CMV and HIV-1 levels were measured in plasma, cervical secretions, and breast milk of 147 HIV-1-infected women to define correlates of maternal CMV replication and infant CMV acquisition.Results. Although few women had detectable CMV in plasma (4.8%), the majority had detectable CMV DNA in cervical secretions (66%) and breast milk (99%). There was a strong association between cervical CMV detection during pregnancy and later breast milk levels (= 0.47; P =. 005). Plasma HIV-1 level and CD4 counts were associated with CMV in the cervix and breast milk. However HIV-1 levels within the cervix and breast milk were not associated with CMV within these compartments. Maternal breast milk CMV levels (hazard ratio [HR], 1.4; P =. 003) and maternal CD4 < 450 cells/mm3 (HR, 1.8; P =. 008) were independently associated with infant CMV acquisition; each log10 increase in breast milk CMV was associated with a 40% increase in infant infection. The breast milk CMV level required to attain a 50% probability of CMV transmission increased with higher maternal CD4 counts, increasing from 3.55 log10 CMV DNA copies/mL at a CD4 count of 350 cells/mm3 to 5.50 log10 CMV DNA copies/mL at a CD4 count of 1000 cells/mm3.Conclusions. Breast milk CMV levels and maternal CD4 count are major determinants of CMV transmission in the setting of maternal HIV-1. Maternal immune reconstitution or lowering breast milk CMV levels may reduce vertical CMV transmission.",

keywords = "compartmentalization, cytomegalovirus, human immunodeficiency virus, neonates, opportunistic infection",

author = "J Slyker and C Farquhar and C Atkinson and K Asbj{\"o}rnsd{\'o}ttir and A Roxby and A Drake and J Kiarie and A Wald and M Boeckh and B Richardson and K Odem-Davis and G John-Stewart and V Emery",

note = "Funding Information: Financial support. This study was supported by K01AI087369 (J. S.) from the National Institute of Allergy and Infectious Diseases (NIAID), and by an Emerging Opportunity Grant (J. S.) from the University of Washington Center for AIDS Research (CFAR), a National Institutes of Health (NIH)–funded program (P30 AI027757), which is supported by the following NIH Institutes and Centers: NIAID, National Cancer Institute, National Institute of Mental Health, National Institute on Drug Abuse, National Institute of Child Health and Human Development, NIH Heart, Lung, and Blood Institute, and the National Institute on Aging. A. D. was supported by a CFAR Training Grant (T32 AI07140-32), and A. R. was a scholar in the International AIDS Research and Training Program, funded by the Fogarty International Center, NIH (D43 TW000007) and was a Fogarty International Clinical Research Fellow (R24 TW007988). V. C. E. is supported through the MRC Centre for Clinical Virology. The randomized trial was conducted with the support of US NIH research grants (R03 HD 057773, R03 HD 057773-02S1, R01 AI076105; K24 AI087399 to C. F.; K24 HD 054314 to G. J. S.; K24 AI071113 and PO1 AI30731 to A. W.; K24 HL093294 to M. B.); a Puget Sound Partners for Global Health Research and Technology Grant; and a University of Washington Royalty Research Fund Grant (to C. F.). GlaxoSmithKline donated study drug and matched placebo but had no role in the study.",

year = "2013",

month = nov,

doi = "10.1093/cid/cit727",

language = "English",

volume = "58",

pages = "564--572",

journal = "Clinical Infectious Diseases",

issn = "1058-4838",

publisher = "Oxford University Press",

number = "4",

}

Slyker, J, Farquhar, C, Atkinson, C, Asbjörnsdóttir, K, Roxby, A, Drake, A, Kiarie, J, Wald, A, Boeckh, M, Richardson, B, Odem-Davis, K, John-Stewart, G & Emery, V 2013, 'Compartmentalized cytomegalovirus replication and transmission in the setting of maternal HIV-1 infection.', Clinical Infectious Diseases, vol. 58, no. 4, pp. 564-572. https://doi.org/10.1093/cid/cit727

TY - JOUR

T1 - Compartmentalized cytomegalovirus replication and transmission in the setting of maternal HIV-1 infection.

AU - Slyker, J

AU - Farquhar, C

AU - Atkinson, C

AU - Asbjörnsdóttir, K

AU - Roxby, A

AU - Drake, A

AU - Kiarie, J

AU - Wald, A

AU - Boeckh, M

AU - Richardson, B

AU - Odem-Davis, K

AU - John-Stewart, G

AU - Emery, V

N1 - Funding Information: Financial support. This study was supported by K01AI087369 (J. S.) from the National Institute of Allergy and Infectious Diseases (NIAID), and by an Emerging Opportunity Grant (J. S.) from the University of Washington Center for AIDS Research (CFAR), a National Institutes of Health (NIH)–funded program (P30 AI027757), which is supported by the following NIH Institutes and Centers: NIAID, National Cancer Institute, National Institute of Mental Health, National Institute on Drug Abuse, National Institute of Child Health and Human Development, NIH Heart, Lung, and Blood Institute, and the National Institute on Aging. A. D. was supported by a CFAR Training Grant (T32 AI07140-32), and A. R. was a scholar in the International AIDS Research and Training Program, funded by the Fogarty International Center, NIH (D43 TW000007) and was a Fogarty International Clinical Research Fellow (R24 TW007988). V. C. E. is supported through the MRC Centre for Clinical Virology. The randomized trial was conducted with the support of US NIH research grants (R03 HD 057773, R03 HD 057773-02S1, R01 AI076105; K24 AI087399 to C. F.; K24 HD 054314 to G. J. S.; K24 AI071113 and PO1 AI30731 to A. W.; K24 HL093294 to M. B.); a Puget Sound Partners for Global Health Research and Technology Grant; and a University of Washington Royalty Research Fund Grant (to C. F.). GlaxoSmithKline donated study drug and matched placebo but had no role in the study.

PY - 2013/11

Y1 - 2013/11

N2 - Background. Cytomegalovirus (CMV) infection is associated with adverse outcomes in human immunodeficiency virus (HIV)-exposed infants. Determinants of vertical CMV transmission in the setting of maternal HIV-1 infection are not well-defined.Methods. CMV and HIV-1 levels were measured in plasma, cervical secretions, and breast milk of 147 HIV-1-infected women to define correlates of maternal CMV replication and infant CMV acquisition.Results. Although few women had detectable CMV in plasma (4.8%), the majority had detectable CMV DNA in cervical secretions (66%) and breast milk (99%). There was a strong association between cervical CMV detection during pregnancy and later breast milk levels (= 0.47; P =. 005). Plasma HIV-1 level and CD4 counts were associated with CMV in the cervix and breast milk. However HIV-1 levels within the cervix and breast milk were not associated with CMV within these compartments. Maternal breast milk CMV levels (hazard ratio [HR], 1.4; P =. 003) and maternal CD4 < 450 cells/mm3 (HR, 1.8; P =. 008) were independently associated with infant CMV acquisition; each log10 increase in breast milk CMV was associated with a 40% increase in infant infection. The breast milk CMV level required to attain a 50% probability of CMV transmission increased with higher maternal CD4 counts, increasing from 3.55 log10 CMV DNA copies/mL at a CD4 count of 350 cells/mm3 to 5.50 log10 CMV DNA copies/mL at a CD4 count of 1000 cells/mm3.Conclusions. Breast milk CMV levels and maternal CD4 count are major determinants of CMV transmission in the setting of maternal HIV-1. Maternal immune reconstitution or lowering breast milk CMV levels may reduce vertical CMV transmission.

AB - Background. Cytomegalovirus (CMV) infection is associated with adverse outcomes in human immunodeficiency virus (HIV)-exposed infants. Determinants of vertical CMV transmission in the setting of maternal HIV-1 infection are not well-defined.Methods. CMV and HIV-1 levels were measured in plasma, cervical secretions, and breast milk of 147 HIV-1-infected women to define correlates of maternal CMV replication and infant CMV acquisition.Results. Although few women had detectable CMV in plasma (4.8%), the majority had detectable CMV DNA in cervical secretions (66%) and breast milk (99%). There was a strong association between cervical CMV detection during pregnancy and later breast milk levels (= 0.47; P =. 005). Plasma HIV-1 level and CD4 counts were associated with CMV in the cervix and breast milk. However HIV-1 levels within the cervix and breast milk were not associated with CMV within these compartments. Maternal breast milk CMV levels (hazard ratio [HR], 1.4; P =. 003) and maternal CD4 < 450 cells/mm3 (HR, 1.8; P =. 008) were independently associated with infant CMV acquisition; each log10 increase in breast milk CMV was associated with a 40% increase in infant infection. The breast milk CMV level required to attain a 50% probability of CMV transmission increased with higher maternal CD4 counts, increasing from 3.55 log10 CMV DNA copies/mL at a CD4 count of 350 cells/mm3 to 5.50 log10 CMV DNA copies/mL at a CD4 count of 1000 cells/mm3.Conclusions. Breast milk CMV levels and maternal CD4 count are major determinants of CMV transmission in the setting of maternal HIV-1. Maternal immune reconstitution or lowering breast milk CMV levels may reduce vertical CMV transmission.

KW - compartmentalization

KW - cytomegalovirus

KW - human immunodeficiency virus

KW - neonates

KW - opportunistic infection

UR - http://europepmc.org/abstract/med/24192386

UR - http://www.scopus.com/inward/record.url?scp=84893217835&partnerID=8YFLogxK

U2 - 10.1093/cid/cit727

DO - 10.1093/cid/cit727

M3 - Article

C2 - 24192386

SN - 1058-4838

VL - 58

SP - 564

EP - 572

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

IS - 4

ER -

Compartmentalized cytomegalovirus replication and transmission in the setting of maternal HIV-1 infection.

Abstract

Bibliographical note

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