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Maternal use of HAART may cause multidrug resistance in breast-feeding infants
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Breast milk from mothers who start postpartum highly active antiretroviral therapy may trigger antiretroviral drug resistance in breast-feeding infants, according to data from the Six Week Extended Nevirapine study.
“Some mothers initiate HAART postpartum for their own health, and an HIV–infected infant who is breast-feeding while the mother is on HAART may be at risk for developing resistance to drugs in the mother’s HAART regimen,” Jessica Lidstrom, of the Johns Hopkins University School of Medicine, said. “The infant could acquire antiretroviral-resistant HIV from transmission of the resistant virus via breast milk or from transfer of low levels of antiretroviral drugs via breast milk.”
Speaking on behalf of researchers from Johns Hopkins University and Emory University in Atlanta, Lidstrom reported that she and colleagues analyzed seven Ugandan infants from the SWEN study to determine whether antiretroviral drug resistance was related to breast-feeding.
All of the infants included in the study were breast-fed and had HIV by 6 weeks old and before initiation of maternal HAART use. The mothers involved began treatment with either D4T/3TC/NVP or ZDV/3TC/NVP by six months postpartum. Additionally, because the analysis involved SWEN study participants, mothers were also assigned to single-dose nevirapine, and infants were assigned to either single-dose nevirapine or single-dose nevirapine with an infant regimen of as long as six weeks of daily nevirapine prophylaxis.
Results indicated that when aged 1 year, all seven infants showed nevirapine resistance with K103N and Y181C mutations. All infants also had the M184V mutation. Six of the infants demonstrated resistance mutations to nucleoside analog reverse transcriptase inhibitors (NRTIs) or non-nucleoside analog reverse transcriptase inhibitors, according to the researchers.
“From this study, we determined that HIV-infected breast-feeding infants can acquire resistance to antiretroviral drugs in their mother’s HAART regimen, and development of resistance to both NNRTIs and NRTIs, [meaning] multiclass resistance, in these HIV-infected infants is likely to significantly reduce the chance of responding to future treatment,” Lidstrom said.
One question raised by an audience member addressed the possibility of transmission of the mother’s mutations to the infant through breast-feeding. Lidstrom explained that the researchers were only able to obtain samples from the infants at 1 year and had no samples of the mothers’ breast milk. Therefore, they could not determine whether maternal transfer of viral mutations took place. – by Melissa Foster
Lidstrom J. #920. Presented at: 17th Conference on Retroviruses and Opportunistic Infections; Feb. 16-19, 2010; San Francisco.