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Prevalence and Predictors of Elevated Aspartate Aminotransferase-to-Platelet Ratio Index in Latin American Perinatally HIV-infected Children

Siberry, George K. MD, MPH*; Cohen, Rachel A. MPH; Harris, D. Robert PhD; Cruz, Maria Leticia Santos MD, MSc; Oliveira, Ricardo MD§; Peixoto, Mario F. MD, MSc; Cervi, Maria Celia MD, PhD; Hazra, Rohan MD*; Pinto, Jorge A. MD, DSc**for the NISDI PLACES Protocol

The Pediatric Infectious Disease Journal: February 2014 - Volume 33 - Issue 2 - p 177–182
doi: 10.1097/INF.0b013e3182a01dfb
HIV Reports

Background: Chronic liver disease has emerged as an important problem in adults with longstanding HIV infection, but data are lacking for children. We characterized elevated aspartate aminotransferase-to-platelet ratio index (APRI), a marker of possible liver fibrosis, in perinatally HIV-infected children.

Methods: The National Institute of Child Health and Human Development International Site Development Initiative enrolled HIV-infected children (ages 0.1–20.1 years) from 5 Latin American countries in an observational cohort from 2002 to 2009. Twice yearly visits included medical history, physical examination and laboratory evaluations. The prevalence (95% confidence interval) of APRI > 1.5 was calculated, and associations with demographic, HIV-related and liver-related variables were investigated in bivariate analyses.

Results: APRI was available for 1012 of 1032 children. APRI was >1.5 in 32 (3.2%, 95% confidence interval: 2.2%–4.4%) including 2 of 4 participants with hepatitis B virus infection. Factors significantly associated with APRI > 1.5 (P < 0.01 compared with APRI ≤ 1.5) included country, younger age, past or current hepatitis B virus, higher alanine aminotransferase, lower total cholesterol, higher log10 current viral load, lower current CD4 count, lower nadir CD4 count, use of hepatotoxic nonantiretroviral (ARV) medications and no prior ARV use. Rates of APRI > 1.5 varied significantly by current ARV regimen (P = 0.0002), from 8.0% for no ARV to 3.2% for non–protease inhibitor regimens to 1.5% for protease inhibitor–based regimens.

Conclusions: Elevated APRI occurred in approximately 3% of perinatally HIV-infected children. Protease inhibitor–based ARVs appeared protective whereas inadequate HIV control appeared to increase risk of elevated APRI. Additional investigations are needed to better assess potential subclinical, chronic liver disease in HIV-infected children.

From the *Maternal and Pediatric Infectious Disease Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda; Westat, Rockville, MD; Department of Infectious Diseases, Hospital Federal dos Servidores do Estado; §Instituto de Puericultura e Pediatria Martagão Gesteira, Universidade Federal do Rio de Janeiro, Rio de Janeiro; Vertical Transmission Unit, Femina Hospital, Porto Alegre; Department of Pediatrics, University of São Paulo Faculty of Medicine of Ribeirão Preto, Ribeirão Preto; and **Department of Pediatrics, Federal University of Minas Gerais, Belo Horizonte, Brazil.

Accepted for publication June 5, 2013.

The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the National Institutes of Health or the Department of Health and Human Services.

This work was supported by the Eunice Kennedy Shriver National Institute of Child Health, NICHD Contract # N01-HD-3-3345 (2002–2007) and by NICHD Contract # HHSN267200800001C (NICHD Control #: N01-HD-8-0001) (2007–2012). The authors have no other funding or conflicts of interest to disclose.

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Address for correspondence: George K. Siberry, MD, MPH, Maternal and Pediatric Infectious Disease Branch, Eunice Kennedy Shriver National Institutes of Child Health and Human Development, National Institutes of Health, 6100 Executive Boulevard, Room 4B11H, Bethesda, MD 20892–7510. E-mail:

© 2014 by Lippincott Williams & Wilkins, Inc.