Hurdles Remain to Reduce Mother-to-Child HIV Transmission

Mother-to-child HIV transmission drives pediatric AIDS incidence, and risk of transmission increases as the mother’s viral load increases.

The Pediatric AIDS Clinical Trials Group Protocol 076 determined that zidovudine can decrease HIV transmission by 70% in nonbreastfed babies. This treatment is given to the mother orally during pregnancy and intravenously during labor, and then the newborn receives the medication orally for 6 weeks.

The INSIGHT START trial sparked a paradigm shift, as clinicians now start highly active antiretroviral therapy (HAART) in all patients regardless of CD4+ count, pregnancy status, or breastfeeding status. As a potential result of this, the infant HIV infection rate decreased by 41% between 2010 and 2014.

When viral load is undetectable, the risk of transmission is less than 1%. Regardless, the US Centers for Disease Control and Prevention recommends that all HIV-positive American mothers avoid breastfeeding because nutritious formula and clean water are available.

The February 2016 issue of the New England Journal of Medicine included a study that detailed advances in HIV prevention and treatment in pediatric patients.

In developing countries, HIV infection progresses considerably faster among children infected at birth than in adults. Around 60% of pediatric patients die within 18 months, and 75% die before age 3 years.

Initial seropositive status because of maternal antibody transfer is a barrier to diagnosis prior to age 18 months. A landmark study found that immediate HAART greatly reduces pediatric mortality by limiting the provirus reservoir volume. Infants infected at birth may eliminate the viral reservoir more quickly than recently infected adults because they start with much smaller reservoirs.

Past attempts to discontinue HAART after years of therapy have mostly failed. Current recommendations warn that HAART cessation is an inappropriate test of persistent remission.

Because HAART options for neonates are limited and have low resistance thresholds,this population needs new approaches. Future therapies may include combining HAART with provirus activators to clear the reservoir followed by CD8+-mediated HIV vaccine to maintain suppression. Gene editing could eliminate the reservoir completely by overwriting the provirus itself.

The world has made great strides in preventing pediatric HIV infection and AIDS. The new challenge is to control, or even eliminate, the viral reservoir.

Current barriers to care include lack of access to maternal care, follow-up, and accurate diagnosis of pediatric infection.