Adverse drug reactions and lipodystrophy in children
Polly Clayden, HIV i-Base
Growth hormone deficiency in children
A poster at ICAAC evaluated the role of human growth Hormone (HGH) deficiency in childhood development and HIV related lipodystrophy .
Ezeanolue and colleagues described three African-American male children (two HIV-positive and one HIV-negative born to an HIV-positive mother), with growth failure, HGH deficiency and low insulin like growth factor 1 (ILGF-1) serum concentrations. The investigators noted that reports of growth hormone (GH) deficiency in HIV positive children are rare. HIV positive children with growth failure are usually found to have opportunistic infections (OI) and low CD4+ T-cell counts but normal GH and ILGF-1 serum concentrations.
All three children had delayed bone development, height and weights below two standard deviation scores. Two children had small pituitary glands on magnetic resonance imaging (MRI) but with replacement GH therapy they have shown good response and regained their growth velocity.
The investigators speculated on the link between this phenomenon and the exposure to nucleoside analogues in utero, since their mothers had all received AZT during pregnancy.
Thyroid dysfunction in children receiving HAART
Although a high rate of thyroid disorders has recently been described in HIV-infected adults treated with HAART, data on children are lacking.
A poster from Vignano and colleagues, whose group in Milan produce consistently excellent work on paediatric metabolic disorders, presented at the lipodystrophy meeting preceding ICAAC. They evaluated 52 HAART treated children from their cohort over six months for signs of thyroid dysfunction .
The investigators found that 19/52 (36.5%) overall showed thyroid abnormalities. They reported that their findings suggested that these abnormalities occurred frequently in HAART-treated children with long lasting immune recovery of viral replication. They identified three associated features: isolated low free thyroxin (FT4) syndrome, sub-clinical hypothyroidism and autoimmune thyroiditis.
The investigators recommend the need for regular monitoring of thyroid function in children receiving HAART.
Therapeutic drug monitoring of efavirenz in pretreated HIV-infected children
It is now fairly well documented that plasma concentrations of antiretrovirals in paediatric patients are extremely variable.
A poster from Breilh and colleagues evaluated the effect of antiretroviral regimens, including the non nucleoside reverse transcriptase inhibitor efavirenz (EFV) on viral load and CD4 cell count in heavily pretreated HIV-infected children, in association with plasma therapeutic drug monitoring (TDM) of EFV.
Sixteen children were assessed over a period of at least two years. Simultaneous PK, virological and immunological parameters were evaluated and plasma EFV concentrations were measured. The target concentration for the EFV trough plasma concentration (C12h) was > 3 µg/ml.
Thirty-two blood samples were obtained 12 hours post dose of EFV. The mean plasma EFV concentration at 12 hours was 1.92 µg/ml and 3.98 µg/ml respectively before and after TDM. Mean doses of EFV were 421 mg/day and 564 mg/day respectively before and after TDM. 13/16 children received 600 mg/day. In comparison with baseline, the children’s viral load decreased by 4.06 log10 and CD4 cell count increased of 267/mm3. 10/16 children achieved a viral load of HIV RNA< 50 copies/ml.
The investigators concluded that: “These results showed the fundamental part of TDM of EFV.” And they continued: “The dose of EFV calculated from the weight of child was not sufficient to obtain an efficacy plasma through (C12h) EFV plasma concentration and could be responsible in the future [for] virological failure.”
Improvement in lipid levels after switching to EFV from PI containing regimens
In an oral presentation McComsey reported the 48 week results of the first PI-switch study in HIV-infected children.
The investigators noted that children might have greater difficulties maintaining viral suppression due to non-adherence and palatability of the drugs. They also pointed out that lipid levels in healthy children vary enormously in age, race and gender. Seventeen children, aged 24-156 months (median 120) were evaluated. All were originally taking a PI-based regimen for 7-50 months (median 35) with HIV-RNA <400 c/ml for 4-55 months (median 13). All children were NNRTI naïve. The PI was switched to EFV while NRTIs were maintained.
All children were heavily pretreated; 88% had prior NRTIs and 41% had prior PI use. The duration of prior ARV therapy was between 21-123 months (median 88). Following the switch to EFV16/17 patients had HIV-1 RNA levels of <50 (in one HIV-1 RNA was 61 c/mL) at wk 48 and CD4% remained stable. Fasting triglycerides, LDL cholesterol levels significantly decreased. There were no significant changes in diet during the study.
The investigators concluded: “Switching to an EFV-containing regimen is safe and well tolerated in children. Fasting triglyceride, total and LDL cholesterol levels decreased significantly.”
- Ezeanolue E, Hardy SL, Nunlee-Bland G et al. Growth Hormone Deficiency in Children with Perinatally Acquired Human Immunodeficiency Virus Infection. Abstract H-1913. Program and Abstracts 42nd Interscience Conference on Antimicrobial Agents and chemotherapy 27-30 September 2002
- Vigano A, Riboni S, Bianchi R et al. High rate of thyroid dysfunction in HIV-infected children receiving highly active antiretroviral therapy. Abstract 96. Program and abstracts 4th International workshop on adverse drug reactions and lipodystrophy in HIV 22-25 September 2002
- Breilh D, Pellegrini I , Douard D. Therapeutic Drug Monitoring of Efavirenz in Pretreated HIV-Infected Children. Abstract H-1710 Program and Abstracts 42nd Interscience Conference on Antimicrobial Agents and chemotherapy 27-30 September 2002
- McComsey G, Bhumbra A, Maa J. Significant Improvement in Lipid Levels Upon Substitution of Protease Inhibitor Therapy with Efavirenz (EFV) in HIV-infected Children. Abstract. H-1081 Program and Abstracts 42nd Interscience Conference on Antimicrobial Agents and chemotherapy 27-30 September 2002