Estimating the efficacy of interventions to prevent mother-to-child transmission of HIV in breast-feeding populations: development of a consensus methodology

Postnatal transmission of HIV through breast milk complicates both the desi gn of effective interventions to prevent mother-to-child transmission of HI V (PMTCT) and their evaluation. Estimated long-term efficacy in five Africa n trials (four with peri-partum antiretrovirals and one with artificial fee ding) varied from 25 to 50 per cent. This variation may be due, at least in part, to differences in analytical methodology. To facilitate direct compa rison between trials, a methodological consensus approach to the analysis a nd presentation of the results of PMTCT trials was developed. The initial m ethodology used and results presented from African trials with available lo ng-term efficacy data were reviewed during a workshop in Bordeaux, France, in September 2000. A consensus approach for evaluating efficacy applicable across PMTCT studies was developed. There are four typical situations defin ed by duration of follow-up (short versus long), and the available demograp hic (vital status) and biological data (single versus repeat HIV testing). Efficacy can be assessed from the risk of infection directly or from HIV-fr ee survival by combining infection and death as a single endpoint. Studies should report results in a standardized format including infection, weaning , mortality and loss to follow-up. New statistical methods that account for the unknown date when a child would first test positive for HIV, for weani ng as a competing risk for HIV infection, and for increased risk of death a mong HIV-infected children should be used in analysing data from PMTCT stud ies with repeat HIV testing. All estimates should be reported with confiden ce intervals. This standardized methodology that allows direct comparison b etween studies is now being applied to four randomized clinical trials. Cop yright (C) 2001 John Wiley & Sons, Ltd.