Nevirapine in pregnancy: benefit persists at one year

The reduction in the risk of mother to baby HIV transmission associated with nevirapine prophylaxis, compared to short course AZT therapy, persists for at least the first year of life despite the ongoing risk posed by breastfeeding. This finding was reported at the 13th International AIDS Conference in Durban today.

The HIVNET 012 study, conducted in Uganda, compared two simple treatment regimens, begun at the onset of labour in HIV-positive women. Women randomised to the nevirapine arm received one dose at the onset of labour, and a second dose was administered to their infant within 72 hours of birth. The second group received AZT throughout labour, and their children received twice daily doses for the first week of life.

Information on the effects of these two regimens on the rate of early mother to baby transmission, assessed at six to eight weeks after delivery, has previously been published in the Lancet. At this timepoint, nevirapine was demonstrated to reduce the risk of HIV transmission by 42%.

96% of the full cohort have completed 12 months of follow-up, and two thirds have reached 18 months. Women in this study breastfed their children, which of course poses an ongoing risk of HIV transmission. As the Durban meeting heard today during the presentation of 18 month data from the PETRA study, which investigated the use of short course AZT/3TC regimens in breastfeeding women, initial differences in transmission rates may fade over time because of the additional risk associated with breastfeeding.

In HIVNET 012, however, results at 12 months suggest that infants born to women who received nevirapine remained at lower risk of HIV infection than those in the AZT arm. At 18 months the risk of transmission was still 42% lower in the nevirapine arm.

Emergence of drug resistance: what are the implications?

A second presentation from the HIVNET 012 study group confirms earlier data that demonstrated the emergence of resistance mutations in a proportion of women (and infants) who received this nevirapine regimen in pregnancy. These data have raised concern over the future efficacy of nevirapine in women who have subsequent pregnancies.

Four of seven women with nevirapine signature mutations six weeks after delivery were genotyped again at 14 to 18 months. All four women had reverted to a wild-type genotype – as would be expected given the long period off treatment, given the lack of selective pressure. Whilst it is possible that resistant mutants remain ‘archived’ as minority sub-species too small to be picked up by resistance testing, this wild-type majority would be expected to remain sensitive to the effects of nevirapine, allowing the drug to be re-used.

This concern aside, the potential benefits of nevirapine prophylaxis remain enticing. An excited Lynn Mofensen of the US National Institutes of Health, commented, “With a regimen with 40% efficacy, we can save 240,000 babies per year”.

As has been widely reported, nevirapine’s manufacturer Boehringer Ingelheim has this week announced a plan to provide nevirapine free of charge for the prevention of mother to baby transmission to any mother who cannot afford to pay for it. According to a BI insider, the company will make the drug available ‘today’ if it is demanded.

The SAINT Study, which investigated the use of a similar nevirapine regimen (see previous news stories here on aidsmap.com), reported a comparable efficacy rate to that seen in HIVNET 012. Whilst the HIVNET regimen involved two doses in total – one to the mother and one to the infant, SAINT provided an additional dose to the mother following delivery. Boehringer, however, plan to employ a two dose regimen in the free drug programme, and may in future manufacture a two dose ‘pregnancy pack’ rather than administer the drug in standard packaging, out of their concern to ensure that these supplies are not used in other indications.