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Concerns over kidney health among children receiving HIV treatment

Ethiopian children living with HIV experienced declining kidney function but improving liver enzymes while on antiretroviral (ARV) treatment, in a recent study.

Researchers at Hawassa University, Ethiopia, the Karolinska Institute, Karolinska University Hospital, Sweden, Oregon Health Sciences University, Management Sciences for Health, Ethiopia and Addis Ababa University, conducted a prospective cohort study of 705 children in southern Ethiopia enrolled in the EPHIC study between October 2015 and October 2016.

Participants had their kidney function and liver enzymes tested at the outset of the study. A respective 615, 554 and 490 children also received such tests at months six, 12 and 18 of the follow-up period. A total of 450 children received all four tests.

The children’s median age was 12 years old. A total of 53.3% were male. Thirty-six (5.1%) were not on ARVs when starting the study. The others had been on HIV treatment for at least three months and for a median of 3.3 years. The children’s liver fibrosis and cirrhosis statuses were assessed using the AST liver enzyme to platelet ratio index (APRI) and fibrosis score (FIB-4) methods.

Upon enrolling in the study, 177 (25.1%) and 83 (11.8%) of the children had elevated AST and ALT liver enzymes, respectively. One in ten children had an APRI score greater than 0.5, suggesting they had liver fibrosis.

Being on an ARV regimen containing Retrovir (zidovudine, or AZT) or Viramune (nevirapine) and having a viral load greater than 1,000 were each significantly associated with having elevated ALT liver enzymes. Retrovir is included in the combination tablets Trizivir (abacavir/zidovudine/lamivudine) and Combivir (zidovudine/lamivudine).

Neither Retrovir nor Viramune are commonly in use in the US anymore. As for indications of compromised kidney health at the beginning of follow-up, 24 (3.4%) and 84 (12.1%) of the participants had elevated creatinine and blood urea nitrogen (BUN), respectively.

For every six months of additional time spent on ARVs, the median BUN increased by 1.6 milligrams per decilitre and the glomerular filtration rate decreased by 35.6 millilitres per minute per 1.73 meters squared. Both of these results are indications of declining kidney health. On the bright side, each additional six months on ARVs decreased both AST and ALT liver enzymes by 1.4 international units per litre.

The study authors characterised the declines in kidney function tests as “worrisome” and said this subject requires further study.

Abstract
Objectives: The aim of the study was to investigate the prevalence of renal function and liver enzyme abnormalities among HIV-infected children, changes in prevalence with time on combination antiretroviral therapy (cART), and the factors associated with these abnormalities.
Methods: A prospective cohort study was conducted among HIV-infected children < 18 years old (n = 705) who were on first-line cART. Liver enzymes, renal function, haematology, immunology and virological response were assessed at enrolment and followed bi-annually for 18 months. Liver fibrosis and cirrhosis were assessed using noninvasive markers including the aspartate aminotransferase (AST) to platelet ratio index (APRI) and fibrosis score (FIB-4). Results: The median age was 12 [interquartile range (IQR) 8-14] years; 53.3% of patients were male. At enrolment, the median cART duration was 3.3 (IQR 1.1-6.1) years; 177 (25.1%) and 83 (11.8%) patients had elevated AST and alanine aminotransferase (ALT), respectively. A tenth of the children had an APRI score > 0.5, suggesting liver fibrosis. Being on a zidovudine (ZDV)- or nevirapine (NVP)-based regimen and having a viral load > 1000 HIV-1 RNA copies/mL were significantly associated with elevated ALT. Twenty-four (3.4%) and 84 (12.1%) patients had elevated creatinine and blood urea nitrogen (BUN), respectively. As cART duration increased by 6 months, median BUN increased by 1.6 [95% confidence interval (CI) 0.4-2.7] mg/dL (P = 0.01); the glomerular filtration rate (GFR) decreased by 35.6 (95% CI 17.7-53.4) mL/min/1.73 m2 (P < 0.0001); and AST and ALT decreased by 1.4 (95% CI 0.4-2.5) IU/L (P = 0.01) and 1.4 (95% CI 0.2-2.6) IU/L (P = 0.01), respectively.
Conclusions: A high prevalence of liver enzyme and renal function abnormalities was observed at enrolment. Decreasing liver enzyme levels during follow-up are possibly reassuring, while the progressive reduction in GFR and the increase in BUN are worrisome and require further study.

Authors
Tadesse BT, Foster BA, Kabeta A, Ayalew F, H/Meskel G, Jerene D, Makonnen E, Aklillu E

[link url="https://www.poz.com/article/concerns-kidney-health-among-children-hiv-treatment"]Poz material[/link]
[link url="https://www.ncbi.nlm.nih.gov/pubmed/30474906"]HIV Medicine abstract[/link]

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