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• W2101674995 abstract "The European Mode of Delivery Collaboration1The European Mode of Delivery CollaborationElective caesarean-section versus vaginal delivery in prevention of vertical HIV-1 transmission: a randomised clinical trial.Lancet. 1999; 353: 1035-1039Summary Full Text Full Text PDF PubMed Scopus (539) Google Scholar found a striking reduction in infant infection with use of elective caesarean section, analysed by intention to treat and actual mode of delivery. They also suggested that planned caesarean section before labour or ruptured membranes should become part of routine care for HIV-positive pregnant women. We find no fault with their methods. However, this study suffers the same fate as many other well-designed therapeutic trials in HIV-1 disease: advances in HIV monitoring and antiretroviral treatment have outpaced the development and conduct of these trials, thereby limiting the generalisability of their results. The investigators do not adequately address the limitations of this study.First, HIV-1 RNA load is an important predictor of maternal-fetal HIV-1 transmission2Coutopoulos-Ioannidis DG Ioannidis JP Maternal cell-free viremia in the natural history of perinatal HIV-1 transmission: a meta-analysis.J Acquir Immune Defic Syndr Hum Retrovirol. 1998; 18: 126-135Crossref PubMed Scopus (48) Google Scholar and relevant to the issue of exposure to infected blood and genital secretions. The main rationale of caesarean-section is to bypass such exposure. This study does not report (perhaps they were not available) or even mention HIV-1 RNA load as a significant variable and possible confounder in the analysis.Second, the dramatic reduction in HIV-1-related morbidity and mortality associated with use of combination antiretroviral therapies has resulted in their use becoming standard of care in the treatment of both pregnant and non-pregnant adults infected with HIV.3DHHS Panel on Clinical Practices for Treatment of HIV InfectionGuidelines for use of antiretroviral agents in HIV-infected adults and adolescents.MMWR Morb Mortal Wkly Rep. 1998; 47 (RR3): 38-78Google Scholar There is no evidence of substantial use of antiretroviral therapy other than zidovudine monotherapy during pregnancy in this study. Highly active antiretroviral therapy, generally involving three agents, results in greater and more sustained reductions of viral load when compared with any one agent alone. Whether the use of more optimum antiretroviral therapy will further reduce HIV-1 transmission over zidovudine alone remains to be seen, but that possibility should not be totally discounted and should have been addressed.Third, there is little doubt that caesarean section, whether elective or emergent, is associated with greater costs and higher likelihood of complications than is vaginal delivery. This study also found a substantial increase in postoperative febrile morbidity in women undergoing caesarean section delivery, although frequency of complications was low. Schuitemaker and co-workers,4Schuitemaker N van Roosmalen J Dekker G et al.Maternal mortality after cesarean section in the Netherlands.Acta Obstet Gynecol Scand. 1996; 75: 332-334Google Scholar in a nationwide study on cause of maternal death, reported a 3·5 times increase in maternal deaths in the Netherlands that was directly attributed to caesarean section, compared with vaginal delivery. Whether HIV status per se or as a surrogate for other risk factors will further increase risk with caesarean section remains unclear. This study, with routine use of prophylactic antibiotics and women largely without much immune compromise, cannot help to answer this question. Nevertheless, this issue has serious implications for practice in the USA and western Europe, but more specifically in less-developed countries, where availability of antibiotics and blood products is limited. In correspondence from a prospective cohort study in Rwanda, three of 20 HIV-positive women undergoing caesarean section died within 72 h from postoperative complications compared with none of ten HIV-negative women. No maternal deaths were seen as a direct result of vaginal delivery.5Bulterys M Chao A Dushimimana A Saah A Fatal complicationss after Caeserian section in HIV-infected women.AIDS. 1996; 10: 923-924PubMed Google ScholarIt is the role of responsible investigators to clearly and effectively call attention to the limitations of their findings and to urge caution in the application of new and potentially unnecessary or dangerous interventions. The European Mode of Delivery Collaboration1The European Mode of Delivery CollaborationElective caesarean-section versus vaginal delivery in prevention of vertical HIV-1 transmission: a randomised clinical trial.Lancet. 1999; 353: 1035-1039Summary Full Text Full Text PDF PubMed Scopus (539) Google Scholar found a striking reduction in infant infection with use of elective caesarean section, analysed by intention to treat and actual mode of delivery. They also suggested that planned caesarean section before labour or ruptured membranes should become part of routine care for HIV-positive pregnant women. We find no fault with their methods. However, this study suffers the same fate as many other well-designed therapeutic trials in HIV-1 disease: advances in HIV monitoring and antiretroviral treatment have outpaced the development and conduct of these trials, thereby limiting the generalisability of their results. The investigators do not adequately address the limitations of this study. First, HIV-1 RNA load is an important predictor of maternal-fetal HIV-1 transmission2Coutopoulos-Ioannidis DG Ioannidis JP Maternal cell-free viremia in the natural history of perinatal HIV-1 transmission: a meta-analysis.J Acquir Immune Defic Syndr Hum Retrovirol. 1998; 18: 126-135Crossref PubMed Scopus (48) Google Scholar and relevant to the issue of exposure to infected blood and genital secretions. The main rationale of caesarean-section is to bypass such exposure. This study does not report (perhaps they were not available) or even mention HIV-1 RNA load as a significant variable and possible confounder in the analysis. Second, the dramatic reduction in HIV-1-related morbidity and mortality associated with use of combination antiretroviral therapies has resulted in their use becoming standard of care in the treatment of both pregnant and non-pregnant adults infected with HIV.3DHHS Panel on Clinical Practices for Treatment of HIV InfectionGuidelines for use of antiretroviral agents in HIV-infected adults and adolescents.MMWR Morb Mortal Wkly Rep. 1998; 47 (RR3): 38-78Google Scholar There is no evidence of substantial use of antiretroviral therapy other than zidovudine monotherapy during pregnancy in this study. Highly active antiretroviral therapy, generally involving three agents, results in greater and more sustained reductions of viral load when compared with any one agent alone. Whether the use of more optimum antiretroviral therapy will further reduce HIV-1 transmission over zidovudine alone remains to be seen, but that possibility should not be totally discounted and should have been addressed. Third, there is little doubt that caesarean section, whether elective or emergent, is associated with greater costs and higher likelihood of complications than is vaginal delivery. This study also found a substantial increase in postoperative febrile morbidity in women undergoing caesarean section delivery, although frequency of complications was low. Schuitemaker and co-workers,4Schuitemaker N van Roosmalen J Dekker G et al.Maternal mortality after cesarean section in the Netherlands.Acta Obstet Gynecol Scand. 1996; 75: 332-334Google Scholar in a nationwide study on cause of maternal death, reported a 3·5 times increase in maternal deaths in the Netherlands that was directly attributed to caesarean section, compared with vaginal delivery. Whether HIV status per se or as a surrogate for other risk factors will further increase risk with caesarean section remains unclear. This study, with routine use of prophylactic antibiotics and women largely without much immune compromise, cannot help to answer this question. Nevertheless, this issue has serious implications for practice in the USA and western Europe, but more specifically in less-developed countries, where availability of antibiotics and blood products is limited. In correspondence from a prospective cohort study in Rwanda, three of 20 HIV-positive women undergoing caesarean section died within 72 h from postoperative complications compared with none of ten HIV-negative women. No maternal deaths were seen as a direct result of vaginal delivery.5Bulterys M Chao A Dushimimana A Saah A Fatal complicationss after Caeserian section in HIV-infected women.AIDS. 1996; 10: 923-924PubMed Google Scholar It is the role of responsible investigators to clearly and effectively call attention to the limitations of their findings and to urge caution in the application of new and potentially unnecessary or dangerous interventions." @default.
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• W2101674995 title "Prevention of vertical HIV-1 transmission" @default.
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