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. 2012;7(12):e51493.
doi: 10.1371/journal.pone.0051493. Epub 2012 Dec 28.

Cell-free (RNA) and cell-associated (DNA) HIV-1 and postnatal transmission through breastfeeding

James Ndirangu  1 , Johannes Viljoen, Ruth M Bland, Siva Danaviah, Claire Thorne, Philippe Van de Perre, Marie-Louise Newell
Affiliations

Cell-free (RNA) and cell-associated (DNA) HIV-1 and postnatal transmission through breastfeeding

James Ndirangu et al. PLoS One. 2012.

Abstract

Introduction: Transmission through breastfeeding remains important for mother-to-child transmission (MTCT) in resource-limited settings. We quantify the relationship between cell-free (RNA) and cell-associated (DNA) shedding of HIV-1 virus in breastmilk and the risk of postnatal HIV-1 transmission in the first 6 months postpartum.

Materials and methods: Thirty-six HIV-positive mothers who transmitted HIV-1 by breastfeeding were matched to 36 non-transmitting HIV-1 infected mothers in a case-control study nested in a cohort of HIV-infected women. RNA and DNA were quantified in the same breastmilk sample taken at 6 weeks and 6 months. Cox regression analysis assessed the association between cell-free and cell-associated virus levels and risk of postnatal HIV-1 transmission.

Results: There were higher median levels of cell-free than cell-associated HIV-1 virus (per ml) in breastmilk at 6 weeks and 6 months. Multivariably, adjusting for antenatal CD4 count and maternal plasma viral load, at 6 weeks, each 10-fold increase in cell-free or cell-associated levels (per ml) was significantly associated with HIV-1 transmission but stronger for cell-associated than cell-free levels [2.47 (95% CI 1.33-4.59) vs. aHR 1.52 (95% CI, 1.17-1.96), respectively]. At 6 months, cell-free and cell-associated levels (per ml) in breastmilk remained significantly associated with HIV-1 transmission but was stronger for cell-free than cell-associated levels [aHR 2.53 (95% CI 1.64-3.92) vs. 1.73 (95% CI 0.94-3.19), respectively].

Conclusions: The findings suggest that cell-associated virus level (per ml) is more important for early postpartum HIV-1 transmission (at 6 weeks) than cell-free virus. As cell-associated virus levels have been consistently detected in breastmilk despite antiretroviral therapy, this highlights a potential challenge for resource-limited settings to achieve the UNAIDS goal for 2015 of eliminating vertical transmission. More studies would further knowledge on mechanisms of HIV-1 transmission and help develop more effective drugs during lactation.

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Conflict of interest statement

Competing Interests: Please note that co-author Dr. Claire Thorne is a PLOS ONE Editorial Board member. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Figure 1
Figure 1. Kaplan-Meier curve showing transmission probabilities after 6 weeks of age.
Figure 2
Figure 2. Distribution of observed log10 cell-free and cell-associated values by age of infant.
Figure 3
Figure 3. Distribution of log10 cell-free and cell-associated values (per ml) by breast and infant age.
See this image and copyright information in PMC

References

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