Worldwide, the primary cause of human immunodeficiency virus (HIV) infection in children is mother-to-child transmission (MTCT). MTCT of HIV can occur during pregnancy, around the time of delivery, or through breastfeeding. Great strides have been made in reducing MTCT during pregnancy and around the time of delivery. However, without intervention, a significant proportion of children born to HIV–infected mothers acquire HIV through breastfeeding.
Where affordable, feasible, acceptable, sustainable, and safe (AFASS) alternatives to breast milk are available, it is recommended that HIV-infected mothers do not breastfeed. However, for a substantial number of HIV-infected women in the developing world, complete avoidance of breastfeeding is not AFASS. These mothers are counseled to practice exclusive breastfeeding (giving a child only breast milk and no additional food, water, or other fluids). Provision of antiretrovirals (ARVs) either to the mother or to the child during breastfeeding represent potential interventions to reduce the risk of HIV transmission to breastfeeding children. This review explores the available evidence regarding the efficacy and safety of ARV prophylaxis regimens to reduce breast milk transmission of HIV.
Antiretroviral prophylaxis, whether used by the HIV-infected mother or the HIV-exposed infant while breastfeeding, is efficacious in preventing mother-to-child transmission of HIV. Further research is needed regarding maternal resistance and response to subsequent antiretroviral therapy after maternal prophylaxis. An ongoing trial (IMPAACT 1077BF) compares the efficacy and safety of maternal triple antiretroviral prophylaxis versus daily infant nevirapine for prevention of mother-to-child transmission through breastfeeding.
An estimated 260,000 children under the age of 15 years acquired HIV infection in 2012. As much as 42% of mother-to-child transmission is related to breastfeeding. Antiretroviral prophylaxis for mothers or infants has the potential to prevent mother-to-child transmission of HIV through breast milk.
To determine which antiretroviral prophylactic regimens are efficacious and safe for reducing mother-to-child transmission of HIV through breastfeeding and thereby avert child morbidity and mortality.
Using Cochrane Collaboration search methods in conjunction with appropriate search terms, we identified relevant studies from January 1, 1994 to January 14, 2014 by searching databases including Cochrane CENTRAL, EMBASE and PubMed, LILACS, and Web of Science/Web of Social Science.
Randomized controlled trials in which HIV-infected mothers breastfed their infants, and in which the mothers used antiretroviral prophylaxis while breastfeeding their children or their children received antiretroviral prophylaxis for at least four weeks while breastfeeding, were included.
Abstracts of all trials identified were examined independently by two authors. We identified 15,922 references and examined 81 in detail. Data were abstracted independently using a standardized form.
Seven RCTs were included in the review.
One trial compared triple antiretroviral prophylaxis during pregnancy and breastfeeding with short antiretroviral prophylaxis to given to the mother to prevent mother-to-child transmission of HIV. At 12 months, the risks of HIV transmission, and of HIV transmission or death, were lower, but there was no difference in infant mortality alone in the triple arm versus the short arm. Using the GRADE methodology, evidence quality for outcomes in this trial was generally low to moderate.
One trial compared six months of breastfeeding using zidovudine, lamivudine, and lopinavir/ritonavir versus zidovudine, lamivudine, and abacavir from 26-34 weeks gestation. At six months, there was no difference in risk of infant HIV infection, infant death, or infant HIV infection or death between the two groups. Evidence quality for outcomes in this trial was generally very low to low.
One trial of single dose nevirapine versus six weeks of infant zidovudine found the risk of HIV infection at 12 weeks to be greater in the zidovudine arm than in the single dose nevirapine arm. Evidence quality for outcomes in this trial was generally very low.
One multi-country trial compared single dose nevirapine and six weeks of infant nevirapine. After 12 months, infants in the extended nevirapine group had a lower risk of infant mortality compared with the control. There was no difference in the risk of HIV infection or death or in HIV transmission alone in the extended nevirapine group compared with the control. Evidence quality for outcomes in this trial was generally low to moderate.
One trial compared single dose nevirapine plus one week zidovudine; the control regimen plus nevirapine up to 14 weeks; or the control regimen with dual prophylaxis up to 14 weeks. At 24 months, the extended nevirapine regimen group had a lower risk of HIV transmission and of HIV transmission or death vs. the control. There was no difference in infant mortality alone. Compared with controls, the dual prophylaxis group had a lower risk of HIV transmission and of HIV transmission or death, but no difference in infant mortality alone. There was no difference in these outcomes between the two intervention arms. Evidence quality for outcomes in this trial was generally moderate to high.
One trial compared six weeks of nevirapine with six months of nevirapine. Among infants of mothers not using highly active antiretroviral therapy, there was no difference in risk of HIV infection among the six month nevirapine group versus the six week nevirapine group. Evidence quality for outcomes in this trial was generally low to moderate.
One trial compared a maternal triple-drug antiretroviral regimen, infant nevirapine, or neither intervention. Infants in the maternal prophylaxis arm were at lower risk for HIV, and HIV infection or death when compared with the control group. There was no difference in the risk of infant mortality alone. Infants with extended prophylaxis had a lower risk of HIV infection and of HIV infection or death versus the control group infants. There was no difference in the risk of infant mortality alone in the extended infant nevirapine group versus the control. There was no difference in HIV infection, infant mortality, and HIV infection or death between the maternal and extended infant prophylaxis groups. Evidence quality for outcomes in this trial was generally low to moderate.