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Mother to child transmission of HIV among Zimbabwean women who seroconverted postnatally: prospective cohort study

BMJ 2010; 341 doi: https://doi.org/10.1136/bmj.c6580 (Published 22 December 2010) Cite this as: BMJ 2010;341:c6580
  1. Jean H Humphrey, associate professor of international health12,
  2. Edmore Marinda, senior statistician13,
  3. Kuda Mutasa, laboratory manager1,
  4. Lawrence H Moulton, professor of international health2,
  5. Peter J Iliff, medical director14,
  6. Robert Ntozini, senior statistician1,
  7. Henry Chidawanyika, data manager1,
  8. Kusum J Nathoo, professor of paediatrics and child health3,
  9. Naume Tavengwa, senior counselling adviser1,
  10. Alison Jenkins, deputy director1, HIV behaviour change communication technical adviser5,
  11. Ellen G Piwoz, director, Center for Nutrition6, senior programme officer7,
  12. Philippe Van de Perre, professor of bacteriology and virology8,
  13. Brian J Ward, professor of infectious diseases and microbiology9
  14. on behalf of the ZVITAMBO study group
  1. 1ZVITAMBO Project, Harare, Zimbabwe
  2. 2Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
  3. 3School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
  4. 4Department of Paediatrics and Child Health, University of Zimbabwe, Harare, Zimbabwe
  5. 5Population Services International, Kigali, Rwanda
  6. 6Academy for Educational Development, Washington, DC, USA
  7. 7Bill and Melinda Gates Foundation, Seattle, WA, USA
  8. 8Laboratory of Bacteriology-Virology, Montpellier University Hospital, Montpellier, France
  9. 9The Research Institute of the McGill University Health Centres, Montreal, Quebec, Canada
  1. Correspondence to: J H Humphrey, ZVITAMBO Project, No 1 Borrowdale Road, Borrowdale, Harare, Zimbabwe jhumphrey{at}zvitambo.co.zw
  • Accepted 22 September 2010

Abstract

Objectives To estimate the rates and timing of mother to infant transmission of HIV associated with breast feeding in mothers who seroconvert postnatally, and their breast milk and plasma HIV loads during and following seroconversion, compared with women who tested HIV positive at delivery.

Design Prospective cohort study.

Setting Urban Zimbabwe.

Participants 14 110 women and infants enrolled in the Zimbabwe Vitamin A for Mothers and Babies (ZVITAMBO) trial (1997-2001).

Main outcome measures Mother to child transmission of HIV, and breast milk and maternal plasma HIV load during the postpartum period.

Results Among mothers who tested HIV positive at baseline and whose infant tested HIV negative with polymerase chain reaction (PCR) at six weeks (n=2870), breastfeeding associated transmission was responsible for an average of 8.96 infant infections per 100 child years of breast feeding (95% CI 7.92 to 10.14) and varied little over the breastfeeding period. Breastfeeding associated transmission for mothers who seroconverted postnatally (n=334) averaged 34.56 infant infections per 100 child years (95% CI 26.60 to 44.91) during the first nine months after maternal infection, declined to 9.50 (95% CI 3.07 to 29.47) during the next three months, and was zero thereafter. Among women who seroconverted postnatally and in whom the precise timing of infection was known (≤90 days between last negative and first positive test; n=51), 62% (8/13) of transmissions occurred in the first three months after maternal infection and breastfeeding associated transmission was 4.6 times higher than in mothers who tested HIV positive at baseline and whose infant tested HIV negative with PCR at six weeks. Median plasma HIV concentration in all mothers who seroconverted postnatally declined from 5.0 log10 copies/mL at the last negative enzyme linked immunosorbent assay (ELISA) to 4.1 log10 copies/mL at 9-12 months after infection. Breast milk HIV load in this group was 4.3 log10 copies/mL 0-30 days after infection, but rapidly declined to 2.0 log10 copies/mL and <1.5 log10 copies/mL by 31-90 days and more than 90 days, respectively. Among women whose plasma sample collected soon after delivery tested negative for HIV with ELISA but positive with PCR (n=17), 75% of their infants were infected or had died by 12 months. An estimated 18.6% to 20.4% of all breastfeeding associated transmission observed in the ZVITAMBO trial occurred among mothers who seroconverted postnatally.

Conclusions Breastfeeding associated transmission is high during primary maternal HIV infection and is mirrored by a high but transient peak in breast milk HIV load. Around two thirds of breastfeeding associated transmission by women who seroconvert postnatally may occur while the mother is still in the “window period” of an antibody based test, when she would test HIV negative using one of these tests.

Trial registration Clinical trials.gov NCT00198718.

Footnotes

  • Members of the ZVITAMBO study group, in addition to the named authors, are: John Hargrove, Agnes Mahomva, Florence Majo, Michael Mbizvo, Faith Mzengeza, Mary Ndhlovu, Lidia Propper, Phillipa Rambanepasi, Andrea Ruff, and Clare Zunguza.

  • Contributors: JHH was the principal investigator of the ZVITAMBO trial, drafted this manuscript, had access to the data, and controlled the decision to publish. JHH also acts as guarantor for the work. EM and LHM designed and conducted the statistical analyses. KM managed all laboratory work. RN and HC designed and implemented the data management system, including calculation of laboratory data. PJI, KJN, NT, EGP, and BJW contributed to the design, implementation, and interpretation of the ZVITAMBO trial. All authors contributed to interpreting the data presented in this paper and to writing this manuscript.

  • Funding: The ZVITAMBO Project was supported by the Canadian International Development Agency (R/C Project 690/M3688); United States Agency for International Development (USAID; cooperative agreement number HRN-A-00-97-00015-00 between Johns Hopkins University and the Office of Health and Nutrition-USAID); a grant from the Bill and Melinda Gates Foundation, Seattle, WA; the SARA Project, operated by the Academy for Educational Development, Washington, DC; and the Department for International Development, United Kingdom (“Saving Maternal and Newborn Lives in the Context of HIV and AIDS in Zimbabwe” Grant No AG 4996 (MIS code 073-555-013 CA 007)). The sponsors of the study had no role in the study design, recruitment of participants, data collection, data analysis, data interpretation, writing of the report, or the decision to submit for publication. The corresponding author had full access to all data and had final responsibility for the decision to submit for publication.

  • Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous 3 years; no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: The Medical Research Council of Zimbabwe, the Medicines Control Authority of Zimbabwe, Johns Hopkins Bloomberg School of Public Health Committee on Human Research, and the Research Institute of the McGill University Health Centres Research Ethics Committee approved the study protocol.

  • Data sharing: Data are available for secondary analyses under some circumstances; please send requests to corresponding author at jhumphrey{at}zvitambo.co.zw.

  • This research was presented in part at the 16th International AIDS Conference, Toronto, Canada; 2006 August 13-18 (poster No MOPEO384).

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