Initiation of ART During Breastfeeding Can Induce Multidrug Resistance in Infants

In resource-limited settings some HIV-positive women initiate ART during breastfeeding. This exposes infected infants to the risk emergence of resistance to the antiretrovirals in their mothers' regimen.

Investigators from the Post Exposure Prophylaxis of Infants (PEPI)-Malawi trial -- in which infants were received up to 14 weeks of extended nevirapine (NVP) or extended NVP plus AZT -- evaluated resistance in infants whose mothers began ART post-partum.

Interim data from this analysis was first presented as a poster at CROI.¹ Further findings were reported in a subsequent article in the April 24 2011 edition of AIDS.²

Infant plasma samples were collected at 14 weeks of age and tested using the ViroSeq HIV Genotyping System and LigAmp -- a sensitive point mutation assay -- to detect K103N (limit of detection 0.5%) and Y181C (limit of detection 1%). Later samples collected at 6 and 12 months of age were also analysed using LigAmp.

The investigators found that at 14 weeks 82/108 (75.9%) of infants evaluated had detectable NVP resistance using the Viroseq assay. The proportion of infants with K103N and/or Y181C detected by LigAmp was similar, 78/108 (72.2%), p=0.45. There were no significant differences between rates of resistance among infants receiving extended NVP or NVP plus AZT measured by either assay. Nor were: duration of prophylaxis received prior to infant diagnosis, maternal CD4 count, maternal single dose NVP use, or in utero infection, significantly associated with NVP resistance.

At 6 months, 38 out of 46 (82.6%) samples analysed still had K103N and/or Y181C. Again, results were similar across study arms, p=1.0. And at 12 months 19 out of 29 (66.5%) evaluable infants had these mutations in similar proportions across arms, p=0.43.

Although the data was not presented, the investigators noted that there was no significant difference in the percentage of the total viral population of either K103N or Y181C in infants in the two groups with these mutations at 6 and 12 months of age.

The investigators concluded that the frequent persistence of the K103N and Y181C mutations in infants after exposure to extended NVP prophylaxis, with or without AZT, may compromise the infants' subsequent response to NNRTI-based treatment.

References

1. Fogel J et al. Initiation of ART in women after delivery can induce multi-class drug resistance in breastfeeding HIV-infected infants: PEPI-Malawi Trial. 18th CROI, 27 February - 2 March 2011, Boston. Poster abstract 761.
2. Fogel J et al. Analysis of nevirapine (NVP) resistance in HIV-infected infants who receive extended NVP or NVP/zidovudine prophylaxis. AIDS 2011 25 911-917.24 April 2011.

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