Nevirapine-resistant HIV present in breastmilk of a third of women exposed to single dose

A third of women who take single-dose nevirapine (Viramune) to prevent mother-to-child transmission of HIV have virus resistant to non-nucleoside reverse transcriptase inhibitors (NNRTIs) present in their breastmilk eight weeks after giving birth, according to a study published in the October 1^st edition of Clinical Infectious Diseases (now online). The investigators also found that almost three quarters of women had detectable HIV in their breastmilk and that women with mastitis – breast tissue inflammation – had significantly higher levels of HIV shedding, leading the researchers to recommend that “interventions to reduce mastitis…are warranted, to increase the safety of breast-feeding and prevent breastmilk transmission of HIV.”

It is estimated that over 600,000 infants were infected with HIV via mother-to-child transmission in sub-Saharan Africa in 2003, and that a third of these infections were due to breast-feeding. Mastitis has been associated with increased viral load in breastmilk and a higher risk of mother-to-child transmission.

Although single-dose nevirapine has been shown to substantially reduce mother-to-child transmission, there is a significant risk that HIV resistance to drugs in the NNRTI class will evolve.

As the effects of single-dose nevirapine are unknown on HIV shedding in breastmilk, investigators in Zimbabwe examined HIV viral load in both breastmilk and blood eight weeks after treatment with the drug was provided. The effect of mastitis on viral load in breastmilk was also determined. NNRTI-resistance mutations in both plasma and breastmilk were also identified.

Thirty-two women were enrolled in the study (HIVNET 023) and all were provided with 200mg of nevirapine at the onset of labour. Viral load in plasma was above 400 copies/ml in 29 (91%) of the women eight weeks after giving birth, with median viral load being 50,000 copies/ml. A total of 23 women (72%) had HIV detectable in their eight-week breastmilk sample, the median viral load being 160 copies/ml.

Mastitis was present in 17 women (57%) and the investigators calculated that these women were 5.4-fold more likely to have viral load levels in their breastmilk above the study median.

Resistance testing indicated that eleven (32%) women had at least one NNRTI mutation present eight weeks after delivery which was not present at baseline. The most common mutation was K103N. Women with resistance mutations had significantly lower CD4 cell counts than women who did not (320 cells/mm³ versus 400 cells/mm³).

Breastmilk samples from 20 women were subjected to resistance testing. Of these 20 samples, 13 (65%) had at least one resistance mutation present.

The investigators then looked at the subset of women who had resistance tests performed on both their plasma and breastmilk samples. They found that ten (50%) had an NNRTI resistance mutation in their plasma and 13 (65%) had NNRTI resistance in their breastmilk. Further analysis showed that the resistance pattern was identical in breastmilk and plasma in ten of the women.

Resistance to drugs from the nucleoside analogue reverse transcriptase inhibitor class (NRTI) was identified in plasma or breastmilk samples from five women.

One infant became infected with HIV whilst breast-fed. Although his mother harboured NNRTI resistant virus, the infant was infected with wildtype HIV.

“The observation of drug-resistant virus in a high proportion of single-dose nevirapine-exposed women who breastfeed their infants is of concern”, comment the investigators.