11 Jun, 12 | by Leslie Goode, Blogmaster
One area in which the recent wide scale deployment of ARV could have the greatest impact is that of mother-to-child HIV transmission (PMTCT). The UNAIDS goal is for total elimination of PMTCT by 2015 – though this is scarcely feasible (STI 2010:86 Suppl.II – especially M. Mahy et al. (http://sti.bmj.com/content/86/Suppl_2/ii48.full?sid=50f44956-1266-4dd0-bed1-08ebd39bb60a)). A component of the PMTCT risk is that of breastfeeding – and a complicating factor here is the need to balance the dangers of PMTCT against the protective effects of breastfeeding in low- medium- resource settings against many of the causes of infant mortality.
Results of the 48-week follow up of the Breastfeeding, Anti-retrovirals and Nutrition (BAN) randomized control trial, conducted 2004-2010 on 2639 breast-feeding HIV+ mothers in Malawi, published in last month’s The Lancet (http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)60321-3/fulltext) indicate some of the complexities involved in making recommendations for resource-poor settings – let alone estimating what it would take to eliminate PMTCT (see above: M. Mahy et al.).
This study is particularly interesting in view of the influence of early findings of this trial in bringing about important changes in the WHO guidelines (2010) on which projections for HIV reduction (STI 2010:86 Suppl.II) were based. Broadly, changes included: 1. an extension of ART to cover six-months of exclusive breastfeeding; 2. dropping of the earlier (2006) recommendations concerning rapid weaning and no mixed feeding (http://www.avert.org/hiv-breastfeeding.htm). Since then (2011) the Kesho Bora study, evaluating of maternal HAART (during pregnancy and breastfeeding) against single dose infant nevirapine, estimated the relative benefit of HAART at 43% (http://sti.bmj.com/content/88/4/313.full?sid=e656a189-e88b-46c9-859f-f719ff4ebf3b.
What more do we learn from the details of the 48-week follow-up in last month’s The Lancet? The relative advantage of ART until weaning at 28 weeks over no ART (4% infant sero-conversion as against 7%) is comparable to earlier findings. A surprise, however, is that 30% of sero-conversions took place after the 28 weeks at which breastfeeding was supposed to have stopped (9 in the maternal ART; 13 in the infant nevirapine; 6 in the control group). This brings home the difficulty of making recommendations that can be applied in contexts where cultural expectations (e.g. mixed feeding or wet nursing of infants, see http://www.time.com/time/health/article/0,8599,1878917,00.html), social pressures or practical constraints must vary widely. The trial also gives details of neonatal and infant morbidity and mortality from any cause until 48 weeks. Mortality stood at 3% for all groups.
In summary, the reduction of sero-conversion by 3% with ART prophylaxis is appreciable but not overwhelming. It has to be set in the context of high levels of infant mortality from causes (e.g. diarrhoea) from which breastfeeding offers considerable protection, and an evident difficulty of complying with recommendations for weaning in low-income settings (which, there is every reason to suppose, will be replicated in non-trial situations). This tends to endorse the thinking behind the 2010 guidelines: namely, that ART prophylaxis is strongly to be recommended for the duration of breast-feeding, but that rapid weaning, and no subsequent mixed feeding, is unlikely to confer any health advantage.
Mary Mahy, Nathan Shaffer et al., “What will it take to achieve virtual elimination of mother-to-child transmission of HIV? An assessment of current progress and future needs”, STI 2010:86 Suppl. II
D. J. Jamieson, C. Van der Horst et al., “Maternal and infant antiretroviral regimens to prevent postnatal HIV-1 transmission: 48-week follow-up of the BAN randomised controlled trial”, The Lancet, online pub., 26th April 2012
M. Desai, “Maternal HAART during breastfeeding confers a 43% RR reduction in mother-to-child transmission of HIV-1”, Clinical Round-up, STI 2011:87:3