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

Abstract

Antiretroviral drugs (ARV) reduce viral replication and can reduce mother-to-child transmission of HIV either by lowing plasma viral load in pregnant women or through post-exposure prophylaxis in their newborns. In rich countries, highly active antiretroviral therapy (HAART) has reduced the vertical transmission rates to around 1-2%, but HAART is not yet widely available in low and middle income countries. In these countries, various simpler and less costly antiretroviral regimens have been offered to pregnant women or to their newborn babies, or to both. To determine whether, and to what extent, antiretroviral regimens aimed at decreasing the risk of mother-to-child transmission of HIV infection achieve a clinically useful decrease in transmission risk, and what effect these interventions have on maternal and infant mortality and morbidity. We sought to identify all relevant studies regardless of language or publication status by searching the Cochrane HIV/AIDS Review Group Trials Register, The Cochrane Library, Medline, EMBASE and AIDSearch and relevant conference abstracts. We also contacted research organizations and experts in the field for unpublished and ongoing studies. The original review search strategy was updated in 2006. Randomised controlled trials of any antiretroviral regimen aimed at decreasing the risk of mother-to-child transmission of HIV infection compared with placebo or no treatment. Two authors independently selected relevant studies, extracted data and assessed trial quality. For the primary outcomes, we used survival analysis to estimate the probability of infants being infected with HIV (the observed proportion) at various specific time-points and calculated efficacy at a specific time as the relative reduction in the proportion infected. Efficacy, at a specific time, is defined as the preventive fraction in the exposed group compared to the reference group, which is the relative reduction in the proportion infected: 1-(Re/Rf). For those studies where efficacy and hence confidence intervals were not calculated, we calculated the approximate confidence intervals for the efficacy using recommended methods. For analysis of results that are not based on survival analyses we present the relative risk for each trial outcome based on the number randomised. No meta-analysis was conducted as no trial assessed the identical drug regimens. Eighteen trials including 14,398 participants conducted in 16 countries were eligible for inclusion in the review. The first trial began in April 1991 and assessed zidovudine (ZDV) versus placebo and since then, the type, dosage and duration of drugs to be compared has been modified in each subsequent trial. Antiretrovirals versus placebo In breastfeeding populations, three trials found that: ZDV given to mothers from 36 to 38 weeks gestation, during labour and for 7 days after delivery significantly reduced HIV infection at 4-8 weeks (Efficacy 32.00%; 95% CI 0.64 to 63.36), 3 to 4 months (Efficacy 34.00%; 95% CI 6.56 to 61.44), 6 months (Efficacy 35.00%; 95% CI 9.52 to 60.48), 12 months (Efficacy 34.00%; 95% CI 8.52 to 59.48) and 18 months (Efficacy 30.00%; 95% CI 2.56 to 57.44). ZDV given to mothers from 36 weeks gestation and during labour significantly reduced HIV infection at 4 to 8 weeks (Efficacy 44.00%; 95% CI 8.72 to 79.28) and 3 to 4 months (Efficacy 37.00%; 95% CI 3.68 to 70.32) but not at birth. ZDV plus lamivudine (3TC) given to mothers from 36 weeks gestation, during labour and for 7 days after delivery and to babies for the first 7 days of life (PETRA 'regimen A') significantly reduced HIV infection (Efficacy 63.00%; 95% CI 41.44 to 84.56) and a combined endpoint of HIV infection or death (Efficacy 61.00%; 95% CI 41.40 to 80.60) at 4 to 8 weeks but these effects were not sustained at 18 months. ZDV plus 3TC given to mothers from the start of labour until 7 days after delivery and to babies for the first 7 days of life (PETRA 'regimen B') significantly reduced HIV infection (Efficacy 42.00%; 95% CI 12.60 to 71.40) and HIV infection or death at 4 to 8 weeks (Efficacy 36.00%; 95% CI 8.56 to 63.44) but the effects were not sustained at 18 months. ZDV plus 3TC given to mothers during labour only (PETRA 'regimen C') with no treatment to babies did not reduce the risk of HIV infection at either 4 to 8 weeks or 18 months. In non-breastfeeding populations, three trials found that: ZDV given to mothers from 14 to 34 weeks gestation and during labour and to babies for the first 6 weeks of life significantly reduced HIV infection in babies at 18 months (Efficacy 66.00%; 95% CI 34.64 to 97.36). ZDV given to mothers from 36 weeks gestation and during labour with no treatment to babies ('Thai-CDC regimen') significantly reduced HIV infection at 4 to 8 weeks (Efficacy 50.00%; 95% CI 12.76 to 87.24) but not at birth ZDV given to mothers from 38 weeks gestation and during labour with no treatment to babies did not influence HIV transmission at 6 months. Longer versus shorter regimens using the same antiretrovirals One trial in a breastfeeding population found that: ZDV given to mothers during labour and to their babies for the first 3 days of life compared with ZDV given to mothers from 36 weeks and during labour (similar to 'Thai-CDC') resulted in HIV infection rates that were not significantly different at birth, 4-8 weeks, 3 to 4 months, 6 months and 12 months. Three trials in non-breastfeeding populations found that: ZDV given to mothers from 28 weeks gestation during labour and to infants for the first 3 days after birth compared with ZDV given to mothers from 35 weeks gestation through labour and to infants from birth to 6 weeks significantly reduced HIV infection rate at 6 months (Efficacy 45.00%; 95% CI 1.88 to 88.12) but compared with the same regimen ZDV given to mothers from 28 weeks gestation through labour and to infants from birth to 6 weeks did not result in a statistically significant difference in HIV infection at 6...