Timing of ART Initiation is Paramount in Perinatal HIV

Patricia M. Flynn, MD

Though they will require critical long-term treatment and monitoring as they age, the use of antiretroviral therapy (ART) for patients with perinatal HIV infection has essentially altered the condition from a fatal diagnosis into a chronic, but manageable, health condition.

In a presentation at the 25^th Conference on Retroviruses and Opportunistic Infections (CROI), in Boston, Massachusetts, Patricia M. Flynn, MD, a professor of pediatrics and preventive medicine at the University of Tennessee’s Health Science Center, spoke about the impact ART has had on the condition, and how far the infectious disease community has come since its initial use.

Although, the sacrifices it took to reach this point were not lost on the Arthur Ashe Chair in AIDS Research and infectious disease specialist at St. Jude Children’s Research Hospital. “Unfortunately, these successes have come too late for many,” Flynn said.

The perinatal transmission of HIV was first identified in the December 17, 1982, issue of the US Centers for Disease Control and Prevention (CDC) Weekly Morbidity and Mortality Report. By 1994, there had been more than 16,000 cases reported, and without treatment, more than 50% of the children diagnosed would die within 2 years.

With the introduction of antiretroviral regimens, the number of cases of perinatal HIV plummeted—the United Nation AIDS data reports that since 2000, 2 million perinatal HIV infections have been prevented—although worldwide there are still roughly 400 new infections of children under the age of 15 daily, and each year in the US, an estimated 69 children are born with HIV.

“We still have quite a bit of a way to go to totally eradicate HIV, but we’re on the way,” Flynn said. “One of the things we’ve learned is that the birth cohort—the year you were born—is probably the strongest predictor of what your outcome and survival will be.”

The reason for this, Flynn said, is due to the availability of more effective HIV therapy, and the ability to initiate that therapy earlier on. The more recent birth cohorts have reduced rates of AIDS and death, and they are more likely to be virally suppressed and have higher CD4 over time.

It is difficult to narrow down how many children are living with perinatal HIV, Flynn noted, but the CIPHER cohort has helped. The Collaborative Initiative for Pediatric HIV Education and Research cohort has a database of 38,187 adolescents with HIV, born between 1982 and 2014.

“[When ART is initiated] is something that’s really key,” Flynn said. Of those in the CIPHER cohort, 88% had received ART, and only 38% had any viral load recorded at any time. In total, 72% had been virally suppressed at their last viral load measurement, which only adds to the proven efficacy of ART, Flynn said.

A major issue in perinatal HIV is the transition of medication responsibilities from the caregiver to the patient—even with the medication available, adherence is a struggle. “The most common reason these patients tell us is that they forgot [to take their medication],” Flynn said. Making the timing of ART initiation and consistency of its utilization paramount, she said.

Patients with perinatal HIV are similar to adults in that they face many complications due to their infection—cardiac, renal, bone, metabolic, and malignancy issues are all challenges that are exacerbated in these patients. However, perinatal HIV brings its own complications.

“One of the things that’s different about pediatrics is that aging up adolescents are unique,” Flynn said. “Both the effects of disease and therapy coincide with the critical periods of growth and development of the body, brain, and immune system.”

For that reason, Flynn highlighted 3 key impacts of the perinatal form: growth failure, delayed puberty, and encephalopathy. All of which are not negatively affected by the treatment but rather the severity of the infection—earlier intervention with ART can improve these outcomes.

Perhaps most important, Flynn said, is the neurodevelopment, especially of the prefrontal cortex. “The effects of HIV and the timing of ART initiation can have a profound impact on neurodevelopment in children and adolescents with HIV,” she said.

If perinatal HIV programs can continue to make an impact to improve these conditions, the future will continue to trend positively, Flynn noted. There is much to learn from the experiences of high-income countries in the treatment of this condition, as more children in lower-income countries present to clinics with perinatal HIV.

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