Antiretrovirals for reducing the risk of mother-to-child transmission of HIV infection

  • Review
  • Intervention

Authors

  • P Brocklehurst,

  • J Volmink


Dr Peter Brocklehurst, Director, National Perinatal Epidemiology Unit, University of Oxford, Old Road Campus, Old Road, Headington, Oxford, OX3 7LF, UK. peter.brocklehurst@npeu.ox.ac.uk.

Abstract

Background

At the end of 2000 it was estimated that over 36 million people were living with the human immunodeficiency virus (HIV). This includes 1.4 million children less than 15 years of age.

This is one of several reviews assessing the available evidence for preventing mother-to-child transmission of HIV infection. The other reviews will address other interventions, including Caesarean section, breast feeding, vaginal lavage and vitamin A supplementation.

Objectives

To assess which antiretroviral therapies may be effective in decreasing the risk of mother-to-child transmission of HIV infection as well as their effect on neonatal and maternal mortality and morbidity.

Search strategy

We searched the Cochrane Pregnancy and Childbirth Group trials register and the Cochrane Controlled Trials Register. We also searched conference abstracts from the International AIDS Conferences and Conference on Retroviruses and Opportunistic Infections.

Selection criteria

Randomised trials comparing any antiretroviral therapy aimed at decreasing the risk of mother-to-child transmission of HIV infection with placebo or no treatment, or any two or more antiretroviral therapies or regimens aimed at decreasing the risk of mother-to-child transmission of HIV infection.

Data collection and analysis

Two reviewers independently extracted data and assessed trial quality.

Main results

Zidovudine monotherapy
Based on four trials any zidovudine regimen versus placebo significantly reduces the risk of mother-to-child transmission (Peto odds ratio (OR) 0.46, 95% confidence interval (CI) 0.35 to 0.60). Zidovudine also appears to decrease the risk of infant death within the first year of birth (OR 0.57, 95% CI 0.38 to 0.85) and the risk of maternal death (OR 0.32, 95% CI 0.16 to 0.66). There is no evidence that zidovudine influences the incidence of premature delivery (OR 0.86, 95% CI 0.57 to 1.29) or low birth weight (OR 0.74, 95% CI 0.53 to 1.04).

The risk of transmission using a 'short-short' course of zidovudine (from 35 weeks in pregnancy for the mother and for the baby until 3 days old) was higher than the risk using a 'long-long' course (from 28 weeks in pregnancy for the mother and for the baby until 6 weeks old), (OR 2.33, 95% CI 1.16 to 4.68). However, the effectiveness of the 'long-short' course (from 28 weeks in pregnancy for the mother and for the baby until 3 days old) and the 'short-long' course (from 35 weeks in pregnancy for the mother and for the baby until 6 weeks old) did not differ from that of the 'long-long' course.

Nevirapine
One large randomised controlled trial demonstrates that nevirapine given to mothers as a single dose at the onset of labour and to babies as a single dose within 72 hours of birth is more effective than an intrapartum and post-partum regimen of zidovudine (OR 0.51, 95% CI 0.33 to 0.79). When nevirapine is given to mothers already receiving standard antiretroviral therapy, however, there appears to be no additional advantage (OR 1.10, 95% CI 0.42 to 2.86).

Combination Therapy
Preliminary findings of the effect of combination therapy using zidovudine and lamivudine (3TC) suggest a decrease in the risk of transmission when the combination is given during the antenatal and intrapartum period or during the intrapartum and postpartum period compared with placebo. There is no evidence that intrapartum zidovudine and lamivudine alone are sufficient to decrease the risk of transmission compared with placebo.

Authors' conclusions

Implications for practice
The randomised trials included in this review provide evidence that short course zidovudine and single-dose nevirapine are effective therapies for reducing mother-to-child transmission of HIV. The challenge for low and middle income countries will be to institute this therapy in practice. In industrialised countries practice has already moved on from the current evidence and combination antiretroviral therapy aimed primarily at preventing disease progression in the mother is the standard of care.

Implications for research
The potential value of nevirapine used for longer durations in breastfeeding populations should be considered as it may further reduce the risk of mother-to-child transmission, particularly if combined with early weaning. On-going evaluation of combination antiretroviral therapy is essential and will have an immediate benefit for countries with the resources to adopt such treatment. The search for effective, affordable, safe and acceptable alternatives to antiretroviral therapy for reducing mother-to-child transmission in resource poor countries should remain on the research agenda.

Plain language summary

Plain language summary

Single doses of nevirapine in labour and for newborn babies reduce mother-to-child HIV transmission, as can short courses of AZT (although longer courses help more)

Antiretroviral therapy (ART) is used to try and prevent transmission of HIV infection from a pregnant, birthing or breastfeeding woman to her baby. The review of trials found that AZT (zidovudine) can reduce mother-to-child HIV transmission and lower the rate of mothers dying within a year. Short course AZT can reduce transmission, but is less effective than longer courses for mother and/or baby. Single doses of nevirapine in labour and for newborn babies reduce transmission, and are better than AZT (alone or in combination with lamivudine - 3TC) used only around labour and birth. ART during breastfeeding might lower transmission further.

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