Abstract
IntroductionTransmission 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 MethodsThirty-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.ResultsThere 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].ConclusionsThe 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.
Highlights
Transmission through breastfeeding remains important for mother-to-child transmission (MTCT) in resourcelimited settings
At 6 months, cell-free and cellassociated levels in breastmilk remained significantly associated with human immunodeficiency virus (HIV)-1 transmission but was stronger for cellfree than cell-associated levels [adjusted hazard ratio (aHR) 2.53 vs. 1.73, respectively]
The findings suggest that cell-associated virus level is more important for early postpartum HIV-1 transmission than cell-free virus
Summary
Transmission through breastfeeding remains important for mother-to-child transmission (MTCT) in resourcelimited settings. In 2010, an estimated 2.7 million people became infected with human immunodeficiency virus (HIV); 1.9 million (70%) of new infections occurred in sub-Saharan Africa (SSA) [1]. An estimated 390,000 (340,000–450,000) new infections occurred in children, 90% of these in SSA, mainly through mother-to-child transmission (MTCT) [1]. MTCT can occur before, during and after delivery, with postnatal transmission through breastfeeding which accounts for one-third to one-half of MTCT remaining an unresolved issue [2]. Postnatal transmission of HIV-1 through breastfeeding is likely to remain an issue for the foreseeable future in resource-limited settings
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