Maternal valacyclovir and infant cytomegalovirus acquisition: a randomized controlled trial among HIV-infected women.

Journal article

Roxby AC, Fullerton, C., Asbjörnsdóttir K, Farquhar C, Kiarie JN, Drake AL, Wald A, Boeckh M, Richardson B, Emery V, John-Stewart G and Slyker JA (2014). Maternal valacyclovir and infant cytomegalovirus acquisition: a randomized controlled trial among HIV-infected women. PLoS ONE. https://doi.org/10.1371/journal.pone.0087855
AuthorsRoxby AC, Fullerton, C., Asbjörnsdóttir K, Farquhar C, Kiarie JN, Drake AL, Wald A, Boeckh M, Richardson B, Emery V, John-Stewart G and Slyker JA
Abstract

Background
Studies in HIV-1-infected infants and HIV-1-exposed, uninfected infants link early cytomegalovirus (CMV) acquisition with growth delay and cognitive impairment. We investigated maternal valacyclovir to delay infant acquisition of CMV.

Methods
Pregnant women with HIV-1, HSV-2 and CD4 count >250 cells/µl were randomized at 34 weeks gestation to 500 mg twice-daily valacyclovir or placebo for 12 months. Maternal CMV DNA was measured in plasma at 34 weeks gestation, in cervical secretions at 34 and 38 weeks gestation, and in breast milk at 7 postpartum timepoints; infant CMV DNA was measured in dried blood spots at 8 timepoints including birth.

Results
Among 148 women, 141 infants were compared in intent-to-treat analyses. Maternal and infant characteristics were similar between study arms. Infant CMV acquisition did not differ between study arms, with 46/70 infants (66%) in placebo arm and 47/71 infants (66%) in the valacyclovir arm acquiring CMV; median time to CMV detection did not differ. CMV DNA was detected in 92% of 542 breast milk specimens with no difference in CMV level between study arms. Change in cervical shedding of CMV DNA between baseline and 38 weeks was 0.40-log greater in the placebo arm than the valacyclovir arm (p = 0.05).

Conclusions
In this cohort of HIV-1-seropositive mothers, two-thirds of infants acquired CMV by one year. Maternal valacyclovir had no effect on timing of infant CMV acquisition or breast milk CMV viral loads, although it modestly reduced cervical CMV shedding. Maternal prophylaxis to reduce infant CMV acquisition warrants further evaluation in trials with antiviral agents.

Year2014
JournalPLoS ONE
PublisherPublic Library of Science (PLoS)
ISSN1932-6203
Digital Object Identifier (DOI)https://doi.org/10.1371/journal.pone.0087855
Publication dates
Print04 Feb 2014
Publication process dates
Accepted24 Dec 2013
Deposited17 May 2023
Publisher's version
License
File Access Level
Open
Permalink -

https://openresearch.lsbu.ac.uk/item/94078

Download files

Publisher's version
file.pdf
License: CC BY 4.0
File access level: Open

  • 80
    total views
  • 15
    total downloads
  • 1
    views this month
  • 0
    downloads this month

Export as

Related outputs

Influenza H1N2 - first human case detected in the UK
Fullerton, C. (2024). Influenza H1N2 - first human case detected in the UK. The Biomedical Scientist Redactive Publishing Limited.
Antibiotic resistance, bacterial transmission and improved prediction of bacterial infection in patients with antibody deficiency
Rofael, S., Babe, C.L., Davrandi, M., Kondratiuk, A.L., Cleaver, L., Ahmed, N., Fullerton, C., McHugh, T. and Lowe, D.M. (2023). Antibiotic resistance, bacterial transmission and improved prediction of bacterial infection in patients with antibody deficiency. JAC-antimicrobial resistance. 5 (6), p. dlad135. https://doi.org/10.1093/jacamr/dlad135
Genomic and geographical structure of human cytomegalovirus
Charles, J., Venturini, C., Gantt, S., Atkinson, C., Griffiths, P., Goldstein, R.S. and Breuer, J. (2023). Genomic and geographical structure of human cytomegalovirus. PNAS. 120 (30), p. e2221797120. https://doi.org/10.1073/pnas.2221797120
A temperature dependent virus binding assay reveals the presence of neutralising antibodies in human cytomegalovirus gB vaccine recipients’ sera
Gomes, A., Baraniak, I., McIntosh, M., Sodi, I., Langstone, T., Siddiqui, S., Fullerton, C., McLean, G., Griffiths, P. and Reeves, M. (2023). A temperature dependent virus binding assay reveals the presence of neutralising antibodies in human cytomegalovirus gB vaccine recipients’ sera. Journal of General Virology. 104 (6). https://doi.org/10.1099/jgv.0.001860
In silico interrogation of the miRNAome of infected haematopoietic cells to predict processes important for human cytomegalovirus latent infection
Fullerton, C., Murray, M. J., Bradley, E., Ng, Y., Thomas, O., Patel, K., Angus, C. and Reeves, M. B. (2023). In silico interrogation of the miRNAome of infected haematopoietic cells to predict processes important for human cytomegalovirus latent infection. Journal of Biological Chemistry. 299 (6), p. 104727. https://doi.org/10.1016/j.jbc.2023.104727
The Cytomegalovirus gB/MF59 vaccine candidate induces antibodies against an antigenic domain controlling cell-to-cell spread
Gomes, A.C., Baraniak, I.A., Lankina, A., Holenya, P., Atkinson, C., Tang, G., Mahungu, T., Kern, F., Griffiths, P.D. and Reeves, M.B. (2023). The Cytomegalovirus gB/MF59 vaccine candidate induces antibodies against an antigenic domain controlling cell-to-cell spread. Nature Communications. 14 (1), pp. 1-12. https://doi.org/10.1038/s41467-023-36683-x
Haplotype assignment of longitudinal viral deep sequencing data using covariation of variant frequencies.
Venturini C, Pang J, Tamuri AU, Roy S, Fullerton, C., Griffiths P, Breuer J and Goldstein RA (2022). Haplotype assignment of longitudinal viral deep sequencing data using covariation of variant frequencies. Virus Evolution. 8 (2), p. veac093. https://doi.org/10.1093/ve/veac093
HCMV carriage in the elderly diminishes anti-viral functionality of the adaptive immune response resulting in virus replication at peripheral sites.
Davies EL, Noor M, Lim EY, Houldcroft CJ, Okecha G, Atkinson C, Reeves MB, Jackson SE, Wills MR and Fullerton, C. (2022). HCMV carriage in the elderly diminishes anti-viral functionality of the adaptive immune response resulting in virus replication at peripheral sites. Frontiers in Immunology. 13. https://doi.org/10.3389/fimmu.2022.1083230
Validation of a commercially available indirect assay for SARS-CoV-2 neutralising antibodies using a pseudotyped virus assay.
Murray MJ, McIntosh M, Fullerton, C., Mahungu T, Wright E, Chatterton W, Gandy M and Reeves MB (2021). Validation of a commercially available indirect assay for SARS-CoV-2 neutralising antibodies using a pseudotyped virus assay. Journal of Infection. 82 (5), pp. 170-177. https://doi.org/10.1016/j.jinf.2021.03.010
Mixed cytomegalovirus genotypes in HIV-positive mothers show compartmentalization and distinct patterns of transmission to infants.
Pang J, Slyker JA, Roy S, Bryant J, Fullerton, C., Cudini J, Farquhar C, Griffiths P, Kiarie J, Morfopoulou S, Roxby AC, Tutil H, Williams R, Gantt S and Breuer J (2020). Mixed cytomegalovirus genotypes in HIV-positive mothers show compartmentalization and distinct patterns of transmission to infants. eLife. https://doi.org/10.7554/elife.63199
A comprehensive characterization of chronic norovirus infection in immunodeficient hosts.
Brown LK, Ruis C, Clark I, Roy S, Brown JR, Albuquerque AS, Patel SY, Miller J, Karim MY, Dervisevic S, Moore J, Williams CA, Cudini J, Moreira F, Lowe DM and Fullerton, C. (2019). A comprehensive characterization of chronic norovirus infection in immunodeficient hosts. Journal of Allergy and Clinical Immunology. 144 (5), pp. 1450-1453. https://doi.org/10.1016/j.jaci.2019.07.036
Seronegative patients vaccinated with cytomegalovirus gB-MF59 vaccine have evidence of neutralising antibody responses against gB early post-transplantation
Baraniak I, Gomes AC, Sodi I, Langstone T, Rothwell E, Atkinson C, Pichon S, Piras-Douce F, Griffiths PD, Reeves MB and Fullerton, C. (2019). Seronegative patients vaccinated with cytomegalovirus gB-MF59 vaccine have evidence of neutralising antibody responses against gB early post-transplantation. EBioMedicine. 50 (19), pp. 45-54. https://doi.org/10.1016/j.ebiom.2019.11.005
High Viral Diversity and Mixed Infections in Cerebral Spinal Fluid From Cases of Varicella Zoster Virus Encephalitis.
Depledge DP, Cudini J, Kundu S, Atkinson C, Brown JR, Haque T, Houldcroft CJ, Koay ES, McGill F, Milne R, Whitfield T, Tang JW, Underhill G, Breuer J and Fullerton, C. (2018). High Viral Diversity and Mixed Infections in Cerebral Spinal Fluid From Cases of Varicella Zoster Virus Encephalitis. Journal of Infectious Diseases. 218 (10), pp. 1592-1601. https://doi.org/10.1093/infdis/jiy358
A collaborative study to establish the 1st WHO International Standard for human cytomegalovirus for nucleic acid amplification technology.
Fryer JF, Heath AB, Minor PD, Collaborative Study Group and Fullerton, C. (2016). A collaborative study to establish the 1st WHO International Standard for human cytomegalovirus for nucleic acid amplification technology. Biologicals. 44 (4), pp. 242-251. https://doi.org/10.1016/j.biologicals.2016.04.005
Islands of linkage in an ocean of pervasive recombination reveals two-speed evolution of human cytomegalovirus genomes
Lassalle, F., Depledge, D.P., Reeves, M.B., Brown, A.C., Christiansen, M.T., Tutill, H.J., Williams, R.J., Einer-Jensen, K., Holdstock, J., Atkinson, C., Brown, J.R., van Loenen, F.B., Clark, D.A., Griffiths, P.D., Verjans, G.M.G.M., Schutten, M., Milne, R.S.B., Balloux, F., Breuer, J. and Fullerton, C. (2016). Islands of linkage in an ocean of pervasive recombination reveals two-speed evolution of human cytomegalovirus genomes. Virus Evolution. 2 (1). https://doi.org/10.1093/ve/vew017
Effects of donor/recipient human leukocyte antigen mismatch on human cytomegalovirus replication following liver transplantation.
Aldridge RW, Mattes FM, Rolando N, Rolles K, Smith C, Shirling G, Fullerton, C., Burroughs AK, Milne RS, Emery VC and Griffiths PD (2015). Effects of donor/recipient human leukocyte antigen mismatch on human cytomegalovirus replication following liver transplantation. Transplant Infectious Disease. https://doi.org/10.1111/tid.12325
Respiratory PCR detects influenza after intranasal live-attenuated influenza vaccination.
Lumley S, Fullerton, C. and Haque T (2013). Respiratory PCR detects influenza after intranasal live-attenuated influenza vaccination. Archives of Disease in Childhood. 99 (3). https://doi.org/10.1136/archdischild-2013-305511
Cytomegalovirus replication kinetics in solid organ transplant recipients managed by preemptive therapy.
Atabani SF, Smith C, Fullerton, C., Aldridge RW, Rodriguez-Perálvarez M, Rolando N, Harber M, Jones G, O'Riordan A, Burroughs AK, Thorburn D and Griffiths PD (2012). Cytomegalovirus replication kinetics in solid organ transplant recipients managed by preemptive therapy. American Journal of Transplantation. 12 (9), pp. 2457-2464. https://doi.org/10.1111/j.1600-6143.2012.04087.x