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Efficacy and safety of caesarean delivery for prevention of mother-to-child transmission of HIV-1

RHL Commentary by Limpongsanurak S

1. EVIDENCE SUMMARY

This review (1) includes one randomized clinical trial which assessed the efficacy of elective Caesarean section delivery for the prevention of mother-to-child transmission of HIV-1, three cohort studies, one secondary data analysis from a clinical trial and one case-control study to assess postpartum morbidity and mortality in HIV-1 infected pregnant women according to mode of delivery.

In the randomized clinical trial, eligible women were randomly assigned to elective Caesarean section delivery at 38 weeks of pregnancy or vaginal delivery. Although some women assigned to the vaginal delivery group eventually delivered by Caesarean section the authors provided analysis according to 'allocated' (intention to treat) and 'received' intervention. The trial found that delivery by elective Caesarean section had lower rate of HIV-1 perinatal transmission in both the allocated and the actual mode of delivery. The odds ratio (OR) and 95% confidence interval (CI) for HIV-1 infection among children were 0.2 and 0–0.8, respectively, for Caesarean section delivery among the women who did not receive zidovudine, and 0.2 and 0–1.7, respectively, among those who did.

The other five studies showed that the incidence of postpartum morbidity and mortality (both minor and major complications) was higher among HIV-1-infected pregnant women who had delivered by Caesarean section compared with those who had delivered vaginally. Incidence rates for postpartum morbidity and mortality were highest for delivery by non-elective Caesarean section, intermediate for delivery by elective Caesarean section and lowest for vaginal delivery.

The authors' methods for literature search were rigorous and all reports of studies that were identified as potentially eligible were assessed. Data extraction, analysis and presentation were clear, precise and concise.

2. RELEVANCE TO UNDER-RESOURCED SETTINGS

2.1. Magnitude of the problem

HIV-1 infection in pregnant women is a worldwide problem. UNAIDS and WHO estimate that at the end of 2005 there were an estimated 17.5 million women worldwide with HIV infection (2). Moreover, in 2005 alone, there were about 700 000 new cases of HIV infection in children under 15 years of age (2). About 90% of HIV-infected children acquire the infection from their mother during pregnancy and childbirth (3, 4). HIV-1 can be transmitted from mother to child during antepartum, intrapartum, and postpartum period (through breast milk).

In most cases mother-to-child transmission of HIV is believed to occur close to or during childbirth. Without antiretroviral prophylactic treatment the transmission rates range between 16% and 25%. In February 1994, the Paediatric AIDS Clinical Trial Group (PACTG) Protocol 076 documented that zidovudine prophylaxis could reduce perinatal HIV-1 transmission by nearly 70% (5). Since 1994, advances have been made in the understanding of the pathogenesis of HIV-1 infection and in the treatment and monitoring of HIV-1 diseases. The rate of perinatal HIV-1 transmission can be reduced to as low as 1–2% with effective highly active antiretroviral therapy (HAART) and formula feeding regardless of mode of delivery. There are many factors influencing perinatal HIV-1 transmission: maternal factors, obstetrical factors and infant factors.

2.2. Applicability of the results

This systematic review demonstrates the benefit of elective Caesarean section delivery among women who either received, or did not receive, zidovudine. Unfortunately, the data are insufficient to evaluate the potential benefit of Caesarean section delivery for neonates of antiretroviral-treated women with plasma HIV-RNA levels below 1000 copies/ml. It is unlikely that scheduled Caesarean section delivery would confer additional benefit in reduction of HIV-1 transmission among this group. There is no evidence from the review to decide whether Caesarean section delivery after membrane rupture or onset of labour is also beneficial in reducing HIV-1 transmission. Incidence rates of morbidity after Caesarean section delivery are higher than with vaginal delivery. Women should be informed about the risks associated with Caesarean section delivery along with the potential benefits expected from this procedure.

2.3. Implementation of the intervention

In under-resourced settings, delivery by elective Caesarean section could be offered in clinics that have the resources to perform such surgery. Elective Caesarean section should be recommended for women on antiretroviral therapy (ART) who have HIV-RNA levels above 1000 copies/ml near delivery. Elective Caesarean section should not be routinely provided to women on ART who have HIV-RNA levels below 1000 copies/ml, unless they choose this procedure after thorough counselling regarding uncertain benefit and known risks. Pregnant women on ART with HIV-RNA levels below 1000 copies/ml should be counseled regarding the low baseline rate of transmission with vaginal delivery and the uncertain benefits and known risks of elective Caesarean section.

In under-resourced settings the costs and the human resource implications of a policy of elective caesarean section to reduce HIV transmission should be taken into account before such a policy is implemented.

3. RESEARCH

Given the low mother-to-child transmission rates among women on HAART, the additional benefit of delivery by elective Caesarean section remain difficult to evaluate in a RCT but is a relevant question to address.

The risk of perinatal HIV-1 transmission increases by 2% with every 1-hour increase in the duration of membrane rupture before delivery in HIV-infected women with <24 hours of membrane rupture regardless of whether women receive zidovudine alone or combination antiretroviral therapy (5). Further research is needed regarding whether elective Caesarean section delivery provides clinically significant benefit to infected women with low or undetectable viral load and to those receiving combination antiretroviral therapy. Further research is also needed to determine the appropriate management of pregnant women with HIV-1 infection who present with ruptured membranes at different points in gestation.

References

• Read JS, Newell ML. Efficacy and safety of cesarean delivery for prevention of mother-to-child transmission of HIV-1. The Cochrane Database of Systematic Reviews;2005, Issue 4.
• UNAIDS/WHO AIDS Epidemic Update 2005. Geneva, UNAIDS, 2005. http://www.unaids.org/epi/2005/doc/report_pdf.asp;.
• Centers for Disease Control and Prevention. HIV/AIDS surveillance report, 2003 (Vol. 15). US Department of Health and Human Services, Centers for Disease Control and Prevention;Atlanta, 2004.
• Minkoff H. Human immunodeficiency virus in pregnancy. Obstet Gynecol 2003;101:797-810.
• The International Perinatal HIV Group. Duration of ruptured membranes and vertical transmission of HIV-1: a meta-analysis from 15 prospective cohort studies. AIDS 2001;15:357-68.

This document should be cited as: Limpongsanurak S. Efficacy and safety of caesarean delivery for prevention of mother-to-child transmission of HIV-1: RHL commentary (last revised: 15 December 2006). The WHO Reproductive Health Library; Geneva: World Health Organization.

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