Abstract
BackgroundThe viral and host factors involved in transmission of HIV through breastfeeding are largely unknown, and intervention strategies are urgently needed to protect at-risk populations. To evaluate the viral and immunological factors directly related to milk transmission of virus, we have evaluated the disease course of Simian Immunodeficiency Virus (SIV) in lactating rhesus macaques (Macaca mulatta) as a model of natural breast milk transmission of HIV.ResultsFourteen lactating macaques were infected intravenously with SIV/DeltaB670, a pathogenic isolate of SIV and were pair-housed with their suckling infants throughout the disease course. Transmission was observed in 10 mother-infant pairs over a one-year period. Two mothers transmitted virus during the period of initial viremia 14–21 days post inoculation (p.i.) and were classified as early transmitters. Peak viral loads in milk and plasma of early transmitters were similar to other animals, however the early transmitters subsequently displayed a rapid progressor phenotype and failed to control virus expression as well as other animals at 56 days p.i. Eight mothers were classified as late transmitters, with infant infection detected at time points in the chronic stage of the maternal SIV disease course (81 to 360 days). Plasma viral loads, CD4+ T cell counts and SIV-specific antibody titers were similar in late transmitters and non-transmitters. Late breast milk transmission, however, was correlated with higher average milk viral loads and more persistent viral expression in milk 12 to 46 weeks p.i. as compared to non-transmitters. Four mothers failed to transmit virus, despite disease progression and continuous lactation.ConclusionThese studies validate the SIV-infected rhesus macaque as a model for breast milk transmission of HIV. As observed in studies of HIV-infected women, transmission occurred at time points throughout the period of lactation. Transmission during the chronic stage of SIV-infection correlated with a threshold level of virus expression as well as more persistent shedding in milk. This model will be a valuable resource for deciphering viral and host factors responsible for transmission of HIV through breastfeeding.
Highlights
The viral and host factors involved in transmission of HIV through breastfeeding are largely unknown, and intervention strategies are urgently needed to protect at-risk populations
We have previously reported breast milk transmission of Simian Immunodeficiency Virus (SIV) in experimentally infected rhesus macaques (Macaca mulatta) [25], and in this report, we expand our observations and examine the correlation between milk transmission of SIV and levels of virus in maternal plasma and milk samples, levels of peripheral CD4+ T cells, and titers of SIV-specific antibodies in milk and plasma from 14 lactating macaques
PCR and Reverse transcription (RT)-PCR analysis of peripheral blood mononuclear cells (PBMC), plasma, spleen, lymph node and thymus obtained at the time of necropsy were all negative for SIV
Summary
The viral and host factors involved in transmission of HIV through breastfeeding are largely unknown, and intervention strategies are urgently needed to protect at-risk populations. Mother-to-infant transmission is the primary cause of HIV-1 infection in children worldwide, with an estimated 700,000 children infected in 2003 [1]. Since breastfeeding is unavoidable in many countries in which the HIV-1 epidemic is most severe, it is necessary to understand risk factors associated with breast milk transmission and the underlying viral and immunological mechanisms responsible for transmission. Epidemiological studies of HIV-1 infected women and their infants have identified several risk factors for milk transmission of HIV, as recently reviewed by Read et al [6]. Conditions affecting the mucosal epithelium, such as mastitis, and oral candidiasis in the infant, have been identified as risk factors for milk transmission of HIV [4,11,12,13]. Several studies have shown that longer durations of breastfeeding increase the cumulative risk of milk transmission [3,4,1416]
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