- Email: [email protected]
Late postnatal mother-to-child transmission of HIV-1
CORRESPONDENCE
which are involved in loss of reflexes and vibration sensation. A cocktail of neurotrophic factors, including NGF and NT-3, may in the future be needed to rescue the full complement of sensory fibres. P Anand Academic Department of Neurology, St Bartholomew’s and the Royal London School of Medicine and Dentistry, London E1 1BB, UK 1 2
3
Larkin M. Nerve growth factor promising in diabetic neuropathy. Lancet 1998; 352: 1039. Anand P, Terenghi G, Warner G, Kopelman P, Sinicropi DV, Williams-Chestnut RE. The role of nerve growth factor in human diabetic neuropathy. Nat Med 1996; 2: 703–07. Anand P. Neurotrophins and peripheral neuropathy. Philos Trans R Soc Lond B Biol Sci 1996; 351: 449–54.
Late postnatal mother-tochild transmission of HIV-1 Sir—We are concerned that the takehome message of Valériane Leroy and colleagues’ meta-analysis (Aug 22, p 597)1 of late postnatal mother-tochild transmission of HIV-1 is misleading. The summary highlights that “if breastfeeding had stopped at age 4 months transmission would have occurred in no infants”. This finding could easily be interpreted to mean that there is no risk of HIV-1 transmission during the first 4 months of breastfeeding, but this is not supported by the study. According to the definition used by Leroy and colleagues, late postnatal transmission of HIV-1 was that occurring after age 2·5 months, so no cases by age 4 months actually means that in those studies no child was infected in the 6-week period between 2·5 and 4 months. Furthermore, children were included in the study only from the date of their first negative HIV-1 test. This test was at a median age of 5·8 months (range 2·5–15·7), so for fewer than half the children with information on timing of acquisition of HIV-1 infection were there any data before age 4 months. Finally, the timing of HIV-1 acquisition was estimated as the midpoint between the last negative and first positive test. We are not told the average interval between tests in the developing country studies. If follow-up was every 3 months as in the developed country cohorts, even for those children followed from age 2·5 months, it would be almost impossible for the estimated acquisition time to fall within the first 4 months of life. The casual reader of this study would conclude that breastfeeding for 4 months is safe. In fact, the report tells
1630
us very little about this early and crucial period. *Judith R Glynn, Laura Rodrigues Infectious Disease Epidemiology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK 1
Leroy V, Newell ML, Dabis F, et al, for the Ghent International Working Group on Mother-to-Child Transmission of HIV. International multicentre pooled analysis of late postnatal mother-to-child transmission of HIV-1 infection. Lancet 1998; 352: 597–600.
Authors’ reply Sir—We agree with Judith Glynn and Laura Rodrigues and indeed our report was not a plea for early cessation of breastfeeding. We would like to stress that our objective was to study the late postnatal transmission of HIV-1, but not to study early postnatal transmission which cannot be distinguished from transmission during delivery. To assess the risk of late postnatal transmission of HIV-1 we used all available information from the various studies in a pooled analysis. For this analysis we applied a standard definition of late postnatal transmission occurring as HIV-1 that was diagnosed after age 2·5 months. Thus, children were included in this analysis from the time of their first negative diagnosis (median age of 5·8 months). Children from developing countries’ studies were usually followed up every 3 months thereafter. As a first step, we decided that if the timing of infection was estimated as the midpoint between the last negative test and the first positive test, then no case was observed before 4 months of age. We suspected that this approach may lead to an overestimate of the benefit of early discontinuation of breastfeeding. Therefore, we repeated the analysis to take account of HIV-1 infection having occurred immediately after the last negative test (then just after 3 months for some children). In that analysis, two of the 20 children would have become infected before age 4 months. We clearly stated in the discussion that our estimation of the risk of late postnatal transmission of 3·2 per 100 child-years of breastfeeding follow-up underestimated the total risk of HIV-1 transmission through breastfeeding since we excluded transmission before age 2·5 months. This risk should be interpreted as an additional risk to the early postnatal risk that remains undefined and needs to be further explored. The take-home message of our multicentre pooled study is that the longer the duration of breastfeeding,
the higher is the cumulative risk of being infected through breastmilk. Finally, we reiterate that the risk of HIV-1 transmission through breastmilk should be balanced against the risk of neonatal mortality and morbidity, before stating that avoiding breastfeeding or early weaning is safe.1 *Valériane Leroy, Marie-Louise Newell, Francois Dabis, Catherine Peckham, Philippe Van de Perre, for the Ghent International Working Group on Motherto-child Transmission of HIV *Unité INSERM 330, Université Victor Segalen Bordeaux 2, 33076 Bordeaux, France; Institute of Child Health, London, UK; and Centre Muraz, Bobo-Dioulasso, Burkina Faso (e-mail: [email protected]) 1
Van de Perre P, Meda N, Cartoux M, Leroy V, Dabis F. Late postnatal transmission of HIV-1 and early weaning. Lancet 1997; 350: 221.
Appropriate technology for cataract surgery Sir—James Tielsch’s Sept 5 commentary1 only examines the role of posterior chamber lenses and makes no reference to the large randomised trial of anterior chamber lens implantation in Nepal published in The Lancet last year.2 Any decision on the most appropriate surgical treatment of cataract should be evidence-based and take account of the effective use of available resources, particularly in developing countries where highvolume, low-cost cataract surgery is usually required. The advantages of using anterior chamber lenses after intracapsular extraction include: less microsurgical technology; less retraining for existing intracapsular extraction surgeons; no posterior capsule left which may opacify at a later date; less expense and shorter time than the extracapsular with posterior chamber lens procedure. The disadvantages of intracapsular extraction include increased vitreousrelated problems, such as cystoid macula oedema and retinal detachment. The old anterior chamber lens prototypes caused corneal problems and uveitis, however, the Nepal study reported that the new open loupe anterior chamber lens has a low complication rate at 1 year, and the 2–5 year follow-up (currently being prepared for publication) confirms a low complication rate with no case of corneal decompensation. The advantages of having an intraocular lens implantation instead of spectacles, which can be lost or broken, are clearly shown. However, improvement in
THE LANCET • Vol 352 • November 14, 1998
which are involved in loss of reflexes and vibration sensation. A cocktail of neurotrophic factors, including NGF and NT-3, may in the future be needed to rescue the full complement of sensory fibres. P Anand Academic Department of Neurology, St Bartholomew’s and the Royal London School of Medicine and Dentistry, London E1 1BB, UK 1 2
3
Larkin M. Nerve growth factor promising in diabetic neuropathy. Lancet 1998; 352: 1039. Anand P, Terenghi G, Warner G, Kopelman P, Sinicropi DV, Williams-Chestnut RE. The role of nerve growth factor in human diabetic neuropathy. Nat Med 1996; 2: 703–07. Anand P. Neurotrophins and peripheral neuropathy. Philos Trans R Soc Lond B Biol Sci 1996; 351: 449–54.
Late postnatal mother-tochild transmission of HIV-1 Sir—We are concerned that the takehome message of Valériane Leroy and colleagues’ meta-analysis (Aug 22, p 597)1 of late postnatal mother-tochild transmission of HIV-1 is misleading. The summary highlights that “if breastfeeding had stopped at age 4 months transmission would have occurred in no infants”. This finding could easily be interpreted to mean that there is no risk of HIV-1 transmission during the first 4 months of breastfeeding, but this is not supported by the study. According to the definition used by Leroy and colleagues, late postnatal transmission of HIV-1 was that occurring after age 2·5 months, so no cases by age 4 months actually means that in those studies no child was infected in the 6-week period between 2·5 and 4 months. Furthermore, children were included in the study only from the date of their first negative HIV-1 test. This test was at a median age of 5·8 months (range 2·5–15·7), so for fewer than half the children with information on timing of acquisition of HIV-1 infection were there any data before age 4 months. Finally, the timing of HIV-1 acquisition was estimated as the midpoint between the last negative and first positive test. We are not told the average interval between tests in the developing country studies. If follow-up was every 3 months as in the developed country cohorts, even for those children followed from age 2·5 months, it would be almost impossible for the estimated acquisition time to fall within the first 4 months of life. The casual reader of this study would conclude that breastfeeding for 4 months is safe. In fact, the report tells
1630
us very little about this early and crucial period. *Judith R Glynn, Laura Rodrigues Infectious Disease Epidemiology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK 1
Leroy V, Newell ML, Dabis F, et al, for the Ghent International Working Group on Mother-to-Child Transmission of HIV. International multicentre pooled analysis of late postnatal mother-to-child transmission of HIV-1 infection. Lancet 1998; 352: 597–600.
Authors’ reply Sir—We agree with Judith Glynn and Laura Rodrigues and indeed our report was not a plea for early cessation of breastfeeding. We would like to stress that our objective was to study the late postnatal transmission of HIV-1, but not to study early postnatal transmission which cannot be distinguished from transmission during delivery. To assess the risk of late postnatal transmission of HIV-1 we used all available information from the various studies in a pooled analysis. For this analysis we applied a standard definition of late postnatal transmission occurring as HIV-1 that was diagnosed after age 2·5 months. Thus, children were included in this analysis from the time of their first negative diagnosis (median age of 5·8 months). Children from developing countries’ studies were usually followed up every 3 months thereafter. As a first step, we decided that if the timing of infection was estimated as the midpoint between the last negative test and the first positive test, then no case was observed before 4 months of age. We suspected that this approach may lead to an overestimate of the benefit of early discontinuation of breastfeeding. Therefore, we repeated the analysis to take account of HIV-1 infection having occurred immediately after the last negative test (then just after 3 months for some children). In that analysis, two of the 20 children would have become infected before age 4 months. We clearly stated in the discussion that our estimation of the risk of late postnatal transmission of 3·2 per 100 child-years of breastfeeding follow-up underestimated the total risk of HIV-1 transmission through breastfeeding since we excluded transmission before age 2·5 months. This risk should be interpreted as an additional risk to the early postnatal risk that remains undefined and needs to be further explored. The take-home message of our multicentre pooled study is that the longer the duration of breastfeeding,
the higher is the cumulative risk of being infected through breastmilk. Finally, we reiterate that the risk of HIV-1 transmission through breastmilk should be balanced against the risk of neonatal mortality and morbidity, before stating that avoiding breastfeeding or early weaning is safe.1 *Valériane Leroy, Marie-Louise Newell, Francois Dabis, Catherine Peckham, Philippe Van de Perre, for the Ghent International Working Group on Motherto-child Transmission of HIV *Unité INSERM 330, Université Victor Segalen Bordeaux 2, 33076 Bordeaux, France; Institute of Child Health, London, UK; and Centre Muraz, Bobo-Dioulasso, Burkina Faso (e-mail: [email protected]) 1
Van de Perre P, Meda N, Cartoux M, Leroy V, Dabis F. Late postnatal transmission of HIV-1 and early weaning. Lancet 1997; 350: 221.
Appropriate technology for cataract surgery Sir—James Tielsch’s Sept 5 commentary1 only examines the role of posterior chamber lenses and makes no reference to the large randomised trial of anterior chamber lens implantation in Nepal published in The Lancet last year.2 Any decision on the most appropriate surgical treatment of cataract should be evidence-based and take account of the effective use of available resources, particularly in developing countries where highvolume, low-cost cataract surgery is usually required. The advantages of using anterior chamber lenses after intracapsular extraction include: less microsurgical technology; less retraining for existing intracapsular extraction surgeons; no posterior capsule left which may opacify at a later date; less expense and shorter time than the extracapsular with posterior chamber lens procedure. The disadvantages of intracapsular extraction include increased vitreousrelated problems, such as cystoid macula oedema and retinal detachment. The old anterior chamber lens prototypes caused corneal problems and uveitis, however, the Nepal study reported that the new open loupe anterior chamber lens has a low complication rate at 1 year, and the 2–5 year follow-up (currently being prepared for publication) confirms a low complication rate with no case of corneal decompensation. The advantages of having an intraocular lens implantation instead of spectacles, which can be lost or broken, are clearly shown. However, improvement in
THE LANCET • Vol 352 • November 14, 1998