In utero exposure to antiretroviral therapy: feasibility of long-term follow-up

Abstract

Most uninfected children born to diagnosed HIV-infected women in the United Kingdom (UK) are exposed to antiretroviral therapy (ART) in utero and neonatally, and concerns exist about potential adverse effects of such exposure. We explored the feasibility of using national clinic-based follow-up to investigate the association between ART exposure and adverse health events occurring after the neonatal period. (33.5%) were enrolled in CHART; parents of 4.8% (100/2104) declined, 2.8% (59/2104) had gone abroad, 21.6% (455/2104) were not contactable, and the remaining 37.3% (786/2104) were not enrolled mainly because of lack of clinic resources or unwillingness of health professionals to approach the families.Demographic characteristics and type of ART exposure for enrolled and non-enrolled children were similar. Latest information on enrolled children was available at a median age of 24 months. Minor childhood ailments were reported in the majority of children, febrile seizures in 1.6% (11/704), and major health problems in 3.8% (27/704). It was 3 reassuring that prevalence of these outcomes was within UK norms, but numbers were small and duration of follow-up was limited.The difficulties encountered in enrolling and retaining children in this study indicate that comprehensive clinic-based follow-up of ART-exposed uninfected children is not practical. Alternative approaches are required; a robust, secure data linkage protocol would provide a more feasible and sustainable system for long term monitoring of in utero ART exposure.4

Pregnancy outcomes in adolescents in the UK and Ireland growing up with HIV

“…Data are currently sparse on the prevalence of congenital abnormalities in the offspring of perinatally infected adolescents. The initial results of follow‐up of antiretroviral‐exposed, HIV‐uninfected infants born to HIV‐positive women appear to be reassuring, with no increase in congenital abnormalities or developmental concerns noted . However, perinatally infected women have been exposed to ART throughout much of their postnatal growth and development.…”

“…It was reassuring that all the births identified by the participating units in this study had also been independently reported to the NSHPC, and were in most cases linked to the mothers’ own paediatric records. However, long‐term follow‐up is likely to prove challenging as previous attempts to maintain follow‐up of children with in utero exposure to ART experienced difficulties in enrolment and retention .…”

Use of Zidovudine-Sparing HAART in Pregnant HIV-Infected Women in Europe: 2000–2009

“…34,35 Although long-term follow-up of uninfected children exposed to ZDV-sparing HAART in utero would be desirable, it is a challenging undertaking. 36 Given the possible adverse effects of in utero exposure to ZDV 37–39 and concerns regarding other drugs, continued pharmacovigilance of all antiretroviral drugs in pregnancy should remain a priority. As clinical trials in pregnancy are not feasible, observational data are needed to provide evidence of the equivalence of newer antiretroviral agents that are not currently licensed for use in pregnancy.…”

Surveillance monitoring for safety of in utero antiretroviral therapy exposures: current strategies and challenges

“…A consented cohort was also established between 2002 and 2005 called the “CHildren exposed to AntiRetroviral Therapy” (CHART) study, which was designed to expand and link to existing NSHPC surveillance data. Of 2104 eligible uninfected children born in the UK between 1996 and 2004, only 34% were enrolled in CHART; most of those not enrolled were either due to lack of clinic resources, inability to contact, or unwillingness of health professionals to approach the families [67]. The CHART team noted that comprehensive clinic-based follow-up of ART-exposed uninfected children is not a feasible strategy in the UK, and recommended exploration of other linkage-based approaches to utilize existing national surveillance data.…”