MTCT programmes short-sighted if no long-term HIV drugs for mums

Treatment programmes which use antiretrovirals to prevent mother to child transmission are likely to succeed only in creating a generation of orphans and ruining the treatment chances of mothers, according to an editorial by prominent US paediatrician Karen Beckerman published today in The Lancet.

She calls for antiretroviral treatment for mothers to be prioritised, noting that the biggest gains in preventing mother to child transmission in the developed world came after the introduction of triple drug antiretroviral therapy.

The editorial accompanies the final publication of findings from the PETRA study, a pan-African investigation of the use of AZT/3TC (zidovudine/lamivudine) in late pregnancy, at the time of delivery and for a week after birth. The study found that whilst transmission in those mothers who received intrapartum treatment, with or without prepartum treatment, was reduced compared to both the placebo and the postpartum treatment only groups in the early months after birth, growing proportions of infants became infected in the 18 month follow-up period due to breast-feeding (18-20%, regardless of which regimen the mother received). The authors note that programmes to prevent mother-to-child transmission will only be partially effective if infection through breastfeeding cannot be addressed.

Dr Beckerman, of San Franciso General Hospital, argues that short-course regimens will compromise the likely effectiveness of any regimens that can be rolled out for widespread use in resource-limited settings in the near future.

"The risks of Petra and other perinatal prophylaxis interventions, such as HIVNET 012, which use single-dose nevirapine intrapartum and neonatally as prophylaxis, have increased in proportion to the increasing probability of access to AIDS treatment in resource-poor settings", she says.

"Treatment success in such regions will hinge on the use of low-pill-burden non-protease-inhibitor combinations, relying on the very classes of drugs used in such studies.

"Is it justifiable to visit the antiretroviral mistakes of the industrialised world on regions that have been devastated by the HIV epidemic but are at least antiretrovirally naive? Active deployment of Petra A or B [prepartum plus intrapartum AZT/3TC or intrapartum treatment only] or the HIVNET 012 protocols for millions of pregnancies (as both teams and

many others advocate) may prevent hundreds of thousands of paediatric infections per year. However, these same women and their infected children exposed to short-course zidovudine plus lamivudine or single-dose nevirapine will be at substantial risk of treatment failure when antiretroviral therapy becomes available. Instead of inducing resistance to AIDS therapies, prophylaxis against mother-to-child transmission must be linked to preventing the creation of orphans."

The nucleoside analogues used in the PETRA study, AZT and 3TC, have been shown to penetrate into breast milk and could thus potentially reduce the risk of HIV transmission through breastfeeding if they form part of a triple regimen given to mothers in the years after birth (Moodley).

"Although support for home care, community programmes, and government services are routinely mentioned as effective responses to the global orphan

tragedy, strategies to prevent the creation of orphans - that is, saving the lives of parents - are rarely discussed. This lack is particularly disturbing in view of the developed world’s experience that treatment of maternal HIV disease results in transmission rates far lower than transmission prophylaxis alone."

An increasing number of governments across Africa, Asia and Latin America are now providing or planning to provide large-scale access to antiretroviral drugs to prevent MTCT, including the governments of Brazil and Thailand which are also working to provide free or widely affordable access to treatment for adults living with HIV. Many of these efforts are supported by international agencies such as UNICEF and by a nevirapine donation programme from Boehringer Ingelheim. The advocates of treatment with AZT (as in Brazil), AZT/3TC (as in Thailand) or nevirapine (as in Uganda and South Africa) have not so far accepted the argument that the risks of spreading antiviral resistance outweigh the opportunity to save the lives and protect the health of babies.

The Elizabeth Glaser Pediatric Foundation, which is funding programmes that could reach 250,000 mothers in Africa and Asia within the next two years, has argued that MTCT programmes will provide a foundation for longer-term access to antiretroviral treatment for mothers. The Foundation will attempt to fund five years-worth of antiretroviral treatment for mothers who are identified as HIV-positive through a programm called MTCT Plus.