Achieving Optimal Neurodevelopmental Outcomes in HIV-Infected Infants

Early detection and robust treatment are critical to limiting deficits in achieving developmental milestones in HIV-infected infants.
Early detection and robust treatment are critical to limiting deficits in achieving developmental milestones in HIV-infected infants.

Human immunodeficiency virus (HIV)-infected infants who achieve viral suppression from antiretroviral therapy (ART) are more likely to partially recover developmental milestones but with persistent deficits compared to uninfected infants, according to an African study published in BMC Pediatrics.1

Previous studies conducted in US cohorts in presymptomatic infants diagnosed with HIV showed better virologic responses to ART were associated with improved achievement of developmental milestones but were still below national averages in noninfected infants.2-6 As more than 90% of neonatal HIV infections occur in sub-Saharan regions of Africa, where diagnosis does not usually occur until after symptom onset,7-10 the investigators focused on an HIV population from Kenya who were symptomatic prior to receiving ART.

A total of 73 HIV-infected infants taking ART (median age 3.7 months) were followed prospectively in comparison to a control group of 92 HIV-unexposed uninfected (HUU) infants (median age 1.6 months), all identified at maternal health clinics or hospitals in Nairobi, Kenya. HIV-infected infants who reached virologic suppression and immune recovery at 6 months showed delays in speech development of approximately 2 months (P =.002), while infants who did not have good response to ART had even greater delays of 5 months (P <.0001). A trend toward a 2-month delay in walking without support at 6 months in the ART-responsive infants increased to 4 months in non-ART-responsive infants.

“Although scores for some domains improved, in general children had scores below a regional norm population after 6 months of ART,” explained lead investigator Sarah Benki-Nugent, MS, PhD, of the department of global health at the University of Washington in Seattle. When asked if improvement in development was likely to continue, she responded, “Some children may catch up, but several factors, including the child's HIV disease severity before starting treatment, the timing of treatment, his or her nutritional status, and the child's home environment and future schooling are also likely very important determinants.”

At the time of enrollment, HIV-infected infants were older than HUU infants by an average of 2 months. They had a median CD4 percentage of 18%, 41.1% (30 patients) had World Health Organization (WHO) stage 3 or 4 HIV, and 52.1% (38 patients) had already been hospitalized. The investigators hypothesized that incomplete recapture of developmental milestones despite effective ART responses may have been related to infectious infiltration of the central nervous system prior to treatment or to incomplete viral clearance after treatment.

These findings support previous research showing that early intervention is the most important factor in retaining cognitive and motor development.11,12 “Altogether, these studies suggest that it is critical to provide additional strategies, such as parenting support for early childhood development, alongside HIV treatment, to help children reach their full potential,” Dr Benki-Nugent said.

“Early HIV diagnosis and treatment is likely the best strategy for achieving optimal neurodevelopmental outcomes in HIV-infected children,” Dr Benki-Nugent reported. “In our study, infants who had robust responses to ART had better outcomes. We have observed similar findings in Kenyan hospitalized HIV-infected children with a new diagnosis and who were aged 0-5. Thus, it is critical for community providers and leaders to understand the potential benefits of early HIV treatment for preserving brain development, and the importance of prompt HIV testing during infancy.”

References

  1. Benki-Nugent S, Wamalwa D, Langat A, et al. Comparison of development milestone attainment in early treated HIV-infected infants versus HIV-unexposed infants: a prospective cohort study. BMC Pediatrics. 2017;17:24. doi:10.1186/s12887-017-0776-1
  2. Crowell CS, Huo Y, Tassiopoulos K, et al; PACTG 219C Study Team and the Pediatric HIVAIDS Cohort Study (PHACS). Early viral suppression improves neurocognitive outcomes in HIV-infected children. AIDS. 2015;29:295-304. doi:10.1097/QAD.0000000000000528
  3. Crowell CS, Malee KM, Yogev R, Muller WJ. Neurologic disease in HIV-infected children and the impact of combination antiretroviral therapy. Rev Med Virol. 2014;24:316-331. doi:10.1002/rmv.1793
  4. Wood SM, Shah SS, Steenhoff AP, Rutstein RM. The impact of AIDS diagnoses on long-term neurocognitive and psychiatric outcomes of surviving adolescents with perinatally acquired HIV. AIDS. 2009;23:1859-1865. doi:10.1097/QAD.0b013e32832d924f
  5. Smith R, Malee K, Leighty R, et al; Women and Infants Transmission Study Group. Effects of perinatal HIV infection and associated risk factors on cognitive development among young children. Pediatrics. 2006;117:851-862.
  6. Smith R, Chernoff M, Williams PL, et al; Pediatric HIV/AIDS Cohort Study (PHACS) Team. Impact of HIV severity on cognitive and adaptive functioning during childhood and adolescence. Pediatr Infect Dis J. 2012;31:592-598. doi:10.1097/INF.0b013e318253844b
  7. Nuwagaba-Biribonwoha H, Werq-Semo B, Abdallah A, et al. Introducing a multi-site program for early diagnosis of HIV infection among HIV-exposed infants in Tanzania. BMC Pediatr. 2010;10:44. doi:10.1186/1471-2431-10-44
  8. Nyandiko WM, Otieno-Nyunya B, Musick B, et al. Outcomes of HIV-exposed children in western Kenya: efficacy of prevention of mother to child transmission in a resource-constrained setting. J Acquir Immune Defic Syndr. 2010;54:42-50. doi:10.1097/QAI.0b013e3181d8ad51
  9. Sibanda EL, Weller IV, Hakim JG, Cowan FM. The magnitude of loss to follow-up of HIV-exposed infants along the prevention of mother-to-child HIV transmission continuum of care: a systematic review and meta-analysis. AIDS. 2013;27:2787-2797. doi:10.1097/QAD.0000000000000027
  10. Mirkuzie AH, Hinderaker SG, Sisay MM, Moland KM, Mørkve O. Current status of medication adherence and infant follow up in the prevention of mother to child HIV transmission programme in Addis Ababa: a cohort study. J Int AIDS Soc. 2011;14:50. doi:10.1186/1758-2652-14-50
  11. Laughton B, Cornell M, Grove D, et al. Early antiretroviral therapy improves neurodevelopmental outcomes in infants. AIDS. 2012;26:1685-1690.
  12. Benki-Nugent S, Eshelman C, Wamalwa D, et al. Correlates of age at attainment of developmental milestones in HIV-infected infants receiving early antiretroviral therapy. Pediatr Infect Dis J.  2015;34:55-61. doi:10.1097/INF.0000000000000526
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