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

• Published in: PloS one Vol. 7; no. 12; p. e51493
• Main Authors: Ndirangu, James, Viljoen, Johannes, Bland, Ruth M, Danaviah, Siva, Thorne, Claire, Van de Perre, Philippe, Newell, Marie-Louise
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 28-12-2012; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; Adult; AIDS; Antiretroviral agents; Antiretroviral drugs; Antiretroviral therapy; Biology; Breast feeding; Breast Feeding - adverse effects; Breast milk; Breastfeeding & lactation; Case-Control Studies; CD4 antigen; Deoxyribonucleic acid; Disease transmission; DNA; DNA, Viral - analysis; Drugs; Female; Health risks; HIV; HIV Infections - transmission; HIV Infections - virology; HIV-1 - genetics; HIV-1 - isolation & purification; HIV-1 - physiology; Human immunodeficiency virus; Humans; Infant; Infant, Newborn; Infectious Disease Transmission, Vertical - statistics & numerical data; Lactation; Medicine; Milk, Human - virology; Postpartum; Postpartum Period; Regression analysis; Ribonucleic acid; Risk Factors; RNA; RNA, Viral - analysis; Shedding; Time Factors; Viruses; Young Adult; France; Africa
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0051493

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.
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.
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].
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.