Maternal nevirapine-based ART more effective if delayed for more than six months after single dose at delivery

Women who received single dose nevirapine at the time of childbirth had better outcomes from nevirapine-based triple combination therapy if they started antiretroviral therapy more than six months after delivery, US researchers report in the January 11^th edition of the New England Journal of Medicine.

Concern about the effectiveness of nevirapine-based antiretroviral therapy for women previously exposed to the drug at the time of delivery centres around the risk that a single dose of the drug may be enough to cause long-lasting resistance. This is because nevirapine levels can take 10-14 days after a single dose to fall below the limits of detection in many women, and throughout this period the potential exists for nevirapine-resistant virus to emerge.

In order to study the effect of peripartum nevirapine exposure on subsequent response to nevirapine-based ART, US researchers from the Botswana-Harvard School of Public Health AIDS Initiative conducted a prospective observational study in Botswana that included 218 postpartum, HIV-infected women who had received nevirapine or placebo at delivery plus a short course of AZT during pregnancy in the previous MASHI study.

Sixty women started nevirapine-based ART within six months of giving birth, and the remaining women began the regimen after that time had passed.

Of the 60 women who started nevirapine-based ART within six months of giving birth, 24 had received a single dose of nevirapine during labour, while 36 had received a placebo. (All of the women in the study were given zidovudine from 34 weeks into their pregnancies through delivery; similar to nevirapine, zidovudine reduces HIV transmission from mother to child.) Of the women in this group who received a single dose of nevirapine during labour, 41.7 per cent subsequently experienced treatment failure, or "virologic failure," within a half a year of starting ART - compared to zero percent among the women in this group who had received placebo during delivery (p

In contrast, there were no statistically significant differences in failure rates within the women who delayed ART for six months - regardless of whether they had received a single dose of nevirapine during labour or not. This group (and additional women who have joined the study since) continues to be followed to ensure that no differences emerge as the women receive treatment over a longer period of time, said Dr Shahin Lockman, lead investigator on the study with Dr Max Essex.

Said Dr Essex: "These results translate into very clear policy for how to treat AIDS in new mothers who received nevirapine to protect their infants. If you can wait six months to administer nevirapine-based ART, do so. If not, treat only with combinations of drugs that do not contain nevirapine or nevirapine-related drugs. Implementing this policy can improve the health of women who need AIDS treatment."

Advice about nevirapine-based regimens also applies to efavirenz-based regimens, since nevirapine and efavirenz are cross-resistant.

Treatment response was also measured among 30 infants in the study who received nevirapine-based ART. More than three-quarters of the 15 infants who were exposed to single dose nevirapine as newborns did not respond adequately to the triple-drug treatment (compared with 9.1 percent of the 15 infants without prior nevirapine exposure).

While these results raise concerns regarding the use of nevirapine-based ART for infants following single-dose nevirapine exposure, said Dr Lockman, the group of infants studied was small, and additional data among infants is needed.

Dr Lockman summarised, "Women who need combination ART for their own health during pregnancy should absolutely receive combination ART whenever possible. However, single-dose nevirapine remains important in preventing mother-to-child transmission of HIV in many locales where it is still the only intervention available. This study provides some important guidance and measured reassurance regarding the timing and effectiveness of nevirapine-based antiretroviral treatment for the many women with AIDS who previously received single-dose nevirapine in labour."