Prevention of Mother-to-Child HIV-1 Transmission—Why We Still Need a Preventive HIV Immunization Strategy

Abstract

There has been dramatic progress in identification of effective interventions to prevent mother-to-child HIV-1 transmission (PMTCT) in low-resource countries and rapid scaleup to implement these interventions in the last 5 years. The proportion of pregnant women tested for HIV-1 in low-resource countries has increased from 7% in 2005 to 26% in 2009, and the proportion of HIV-1–infected pregnant women receiving antiretroviral prophylaxis has increased from 15% in 2005 to 53% in 2009. A 24% reduction in estimated annual new infant HIV-1 infections was observed between 2005 and 2009 in the 25 low-resource countries, where approximately 91% of HIV-1–infected pregnant women reside. Joint United Nations Program on HIV/AIDS (UNAIDS) has developed a plan for global virtual elimination of mother-to-child HIV-1 transmission (MTCT), with a goal to reduce the number of new infant HIV-1 infections by 90% and MTCT to ,5% between 2009 and 2015. However, we remain far short of the goal of global MTCT elimination. In 2009, there remained an estimated 347,000 new infant infections in the 25 countries discussed above, with 40%–50% of these infections acquired through breastfeeding. Optimal prevention requires identification of maternal HIV-1 infection early in pregnancy with prompt initiation of antiretroviral drugs for treatment or prophylaxis, yet many women in lowresource countries access prenatal care late, only at delivery or do not deliver in medical settings. Provision of the infant PMTCT antiretroviral prophylaxis component remains low, with coverage increasing only slightly from 32% in 2008 to 35% in 2009. Although current World Health Organization guidelines now recommend breastfeeding for 12 months with concurrent infant or maternal antiretroviral prophylaxis, new reports suggest weaning before age 18 months is associated with elevated morbidity and mortality and that reduced risk of diarrhea-related morbidity and mortality among HIV-1–exposed uninfected children is associated with continuing breastfeeding after age 12 months even when replacement and complementary foods and counseling are provided. Thus, interventions to allow safe breastfeeding longer than 12 months are important to optimize infant survival. Finally, HIV-1 seroconversion rates of 3%–10% in uninfected pregnant or lactating women have been reported in HIV-1 endemic settings, which are associated with high risk of MTCT; it is estimated that 40% of new infant infections in Botswana are due to acute maternal infection during pregnancy or lactation. Although antiretroviral prophylaxis significantly reduces MTCT, effective implementation is complicated by need for prolonged drug administration and adherence, potential toxicities leading to continued monitoring requirements, potential for drug resistance, and inadequate health-care infrastructure. Additionally, even with maternal triple-drug prophylaxis, most studies demonstrate cumulative residual MTCT rates of 2%–5% at age 6 months. Thus, continued investigation of preventive immunologic interventions including maternal and/or infant passive/active immunization to reduce MTCT remains important. Although antiretroviral prophylaxis is the foundation for PMTCT, immunization strategies could provide a safe and durable adjunctive intervention to prevent transmission, particularly during breastfeeding. Immunization strategies, if found to be efficacious, have the advantage of being less reliant on patient adherence and health-care infrastructure than are drug interventions.