Low effectiveness of nevirapine to reduce MTCT in real life situation

6 November 2004. Related: Pregnancy.

Polly Clayden, HIV i-Base

A research letter in the 3 September edition of AIDS discusses the effectiveness of nevirapine in reducing mother to child transmission in a field setting in Mombasa, in which mother to child transmission rates were similar to those found using no intervention.

The authors point out that although the HIVNET012 regimen has been widely recommended, data to validate the effectiveness of this strategy outside a research setting are lacking.

In the study – conducted between April 2001 and October 2003 – HIV-positive women received nevirapine and instructions to use it at the onset of labour, and were invited to participate in the follow up study. Infant blood was taken at 6 and 14 weeks and DNA PCR were performed. When no sample was available at 6 weeks, the result of the 14-week sample was used to calculate transmission rates, when there was no 14 week result and the 6-week sample was negative, the results were not included in the calculation of the overall perinatal transmission rate. A child was considered HIV positive when the 6-week sample was positive and the 14-week sample missing.

The programme enrolled 482 women, and 172 presented for follow up at 6 or 14 weeks. The investigators report, over 58% of the women delivered at the hospital, 19% delivered at home, and 22% delivered in another hospital. More than 85% of the women (147/172) reported taking the maternal dose, 86.0% of babies (148/172) received the nevirapine suspension, and 82% (141/172) reported the administration of both the maternal and neonatal dose.

Samples were available for 127 babies, and the authors report a transmission rate of 18.1% at 14–16 weeks. They write that there was no correlation between the maternal dose intake only, intake by the baby only, or the intake of nevirapine by both mother and baby, and the transmission rates at 14 weeks (p= 0.887, p=0.336 and p= 0.529, respectively).

The authors write that this transmission rate is similar to a perinatal transmission rate at 14 weeks of 21.7% using no intervention in this Mombasa setting, and does not compare well to the HIVNET012 reported rate of 13.1% at 14 weeks.

The authors add: “These data, suggesting a rather limited effect of the widely recommended HIVNET012 intervention, call for further research on the long-term efficacy of the HIVNET012 regimen in a field setting. Taking into account the low coverage of the nevirapine regimen, the lack of benefit for maternal health, the concerns about resistance, the enormous deployment of resources needed to provide nevirapine within the current voluntary counselling and testing paradigm, and the reported lack of efficacy in real life conditions, the true health gains of the intervention should be reconsidered.”

Comment

Two articles are presented with data and analysis which result in assessments of the potential financial cost and clinical effectiveness of single dose maternal plus single dose infant nevirapine for the prevention of mother-to-child transmission of HIV-1 that differ from earlier studies.

The findings are not particularly surprising and will continue the swing of the pendulum away from this approach which might have begun when the first reports of nevirapine resistance in mothers following single dose exposure were reported – by Eshleman et al – from HIVNET012 but certainly gained momentum in February 2004 when Jourdain et al reported the negative impact of these mutations on maternal treatment at six months.

It is clear to most that single dose nevirapine is not the panacea of MTCT. The trick now is not to throw the baby out with the bathwater. Nevirapine is a highly effective HIV RT inhibitor which efficiently crosses the placenta and which has a long plasma half-life that can be used to advantage. Lallemant et al showed that used in combination with zidovudine monotherapy from 28 weeks single dose nevirapine contributes significantly to reducing pre/intrapartum transmission to 2%. While McIntyre et al demonstrated the addition of Combivir for 4 – 7 days post-partum dramatically limits the development of detectable nevirapine resistance mutations in plasma at 12 days. Whether these two approaches can be successfully combined and the determination of the optimal duration and components of therapy to preserve the use of nevirapine is the next priority.

Meanwhile we should not forget that the prevention of paediatric HIV infection as well as the survival of HIV uninfected children starts with prevention of HIV infection in their parents and with treating those mothers already infected if this is indicated for their own HIV. The point is already implicit in the cost effectiveness analysis but could stand a little more emphasis, some have speculated that all the infrastructure needed for 012 is just about what is needed for treatment.

The study also reminds us: “The goal in the Declaration on HIV/AIDS of the UN General Assembly Special Session is bold in its mandate, ‘reduce the proportion of infants infected with HIV by 20% by 2005, and by 50% by 2010’. We are very unlikely to reach this goal if we concentrate on MTCT single dose nevirapine interventions in isolation.

Reference:

Quaghebeura A, Mutungab L, Mwanyumbac F et al. Low efficacy of nevirapine (HIVNET012) in preventing perinatal HIV-1 transmission in a real life situation. AIDS: Vol 18(13), 3 September. Research Letters 1855.