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Review
Does maternal HSV-2 coinfection increase mother-to-child transmission of HIV? A systematic review
  1. Vishalini Sivarajah1,
  2. Kevin Venus1,
  3. Mark H Yudin2,3,
  4. Kellie E Murphy3,4,
  5. Steven A Morrison1,
  6. Darrell HS Tan5,6,7
  1. 1 Faculty of Medicine, University of Toronto, Toronto, Canada
  2. 2 Department of Obstetrics and Gynaecology, St. Michael’s Hospital, Toronto, Canada
  3. 3 Department of Obstetrics and Gynaecology, University of Toronto, Toronto, Canada
  4. 4 Department of Obstetrics and Gynaecology, Mount Sinai Hospital, Toronto, Canada
  5. 5 Division of Infectious Diseases, St. Michael’s Hospital, Toronto, Canada
  6. 6 Centre for Urban Health Solutions, St. Michael’s Hospital, Toronto, Ontario, Canada
  7. 7 Department of Medicine, University of Toronto, Toronto, Ontario, Canada
  1. Correspondence to Darrell HS Tan, Division of Infectious Diseases, St. Michael’s Hospital, Toronto, ON M5B 1W8, Canada; darrell.tan{at}gmail.com

Abstract

Background Reducing HIV mother-to-child transmission (MTCT) is critical to ending the HIV pandemic. Reports suggest that herpes simplex virus-2 (HSV-2), a common coinfection in HIV-infected individuals, is associated with increased MTCT, but results have been conflicting. We conducted a systematic review of observational studies to quantify the magnitude of this relationship (PROSPERO no. CRD42016043315).

Methods We searched Medline (1981 to June week 3, 2016), EMBASE (1981 to week 26, 2016), relevant conferences (2013–2016) and bibliographies of identified studies for cohort and case–control studies enrolling HIV-positive women during pregnancy or peripartum that quantified the effect of HSV-2 infection on MTCT. The primary outcome was the risk of perinatal HIV transmission associated with maternal HSV-2 status. Risk of bias was evaluated using a standardised tool, and results were meta-analysed where appropriate using a random-effects model, with studies weighted using the inverse variance method.

Results From 2103 hits, 112 studies were considered for inclusion, and 10 were ultimately included. Of the included studies, three used a case–control design, three were retrospective cohorts and four were prospective cohorts. Risk of bias was low in three studies, moderate in six and high in one. The median sample size was 278.5 mother–infant pairs (range: 48–1513). The most common strategy for classifying maternal HSV-2 status was type-specific serology (n=6), followed by genital shedding (n=3) or genital culture (n=3), clinical diagnosis of herpes (n=2) or genital ulcer disease (n=1). Results from five studies that provided quantitative estimates of the association between HSV-2 seropositivity and MTCT were meta-analysed, yielding a pooled unadjusted OR=1.17 (95% CI=0.69 to 1.96, I2=58%). Three of these studies further considered key confounding variables, specifically antiretroviral use and/or viral load (n=3), and mode of delivery (n=2), yielding a pooled adjusted OR=1.57 (95% CI=1.17 to 2.11, I2=0).

Conclusions Maternal HSV-2 coinfection appears to be associated with increased perinatal HIV transmission. Further study of the effect of HSV-2 treatment on MTCT is warranted.

  • herpesvirus-2
  • HIV
  • transmission
  • coinfection
  • infant
  • mother
  • human

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/sextrans-2016-052921

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    Footnotes

    • Acknowledgements We thank Elizabeth Uleryk for her assistance in developing and conducting the search strategy for this systematic review.

    • Contributors All authors contributed significantly to the work, as follows: DHST conceived the study idea; DHST designed the protocol in consultation with MHY and KEM; VS and KV conducted database searches; VS, KV, SAM and DHST selected eligible articles for inclusion; KV and VS conducted the data extraction; DHST, KV and VS designed and conducted the statistical analysis; VS and DHST wrote the original draft of the manuscript; all authors provided critical input into and approved the final version of the manuscript.

    • Funding DHST is supported by a New Investigator Award from the Canadian Institutes of HealthResearch / Ontario HIV Treatment Network.

    • Competing interests DHST has received honouraria from Abbvie, Gilead, Merck and Viiv Healthcare, has been awarded grants for investigator-initiated studies from Gilead and Viiv Healthcare and is a site principal investigator for clinical trials sponsored by GSK.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Correction notice This paper has been amended since it was published Online First. Owing to a scripting error, some of the publisher names in the references were replaced with ’BMJ Publishing Group'. This only affected the full text version, not the PDF. We have since corrected these errors and the correct publishers have been inserted into the references.