Protease inhibitor therapy improves protein catabolism in prepubertal children with HIV infection.
Past studies in adults have reported that loss of lean tissue mass (LTM) is associated with accelerated rates of protein catabolism. To date, studies of protein kinetics from pediatric patients infected by HIV have not been published; however, poor linear growth and weight loss are well-documented. The first aim of this study was to test the hypothesis that protein catabolism is high in pediatric patients with HIV. Protease inhibitors (PI) have proven to be effective therapy for pediatric HIV patients. One action of these drugs is that of lowering the viral burden, and several studies suggest that these drugs result in increased growth and weight velocity. Our second aim was to determine whether PI therapy improves protein catabolism.


METHODS
We studied eight children infected with HIV (ages 2.9-6.2 years, Tanner stage I, CD4 counts 100,000-300,000, 5 F/3 M) and eight healthy age- and gender-matched controls. Measures of protein turnover were conducted using the stable isotope [1-(13C)]leucine. Body composition was measured by dual X-ray absorptiometry (DXA) scan for determination of LTM, and indirect calorimetry for measurement of resting energy expenditure. Children with HIV infection were studied at baseline and after 6 weeks of PI therapy; control children were studied only once.


RESULTS
Protein catabolism, represented as leucine rate of appearance (Ra) in the fasted state, was higher in the HIV-infected children at baseline compared to control children. After 6 weeks of PI therapy, leucine Ra decreased, but not to the range found in control children. Leucine Ra correlated with viral burden. LTM significantly improved in all patients.


CONCLUSIONS
These results suggest that similar to HIV-infected adults, HIV-infected children have higher than normal protein catabolism. Furthermore, our measures suggest that short-term PI therapy results in improved protein catabolism and LTM.
Hardin
Dana S
DS
Department of Pediatrics, University of Texas-Southwestern Medical School, Houston 77030, USA. dana.hardin@utsouthwestern.edu
Ellis
Kenneth J
KJ
Rice
Julie
J
Doyle
Marilyn E
ME
D001823:Body Composition / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D018791:CD4 Lymphocyte Count / Q000379:methods; D002247:Carbon Isotopes / Q000008:administration & dosage / Q000097:blood; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D004334:Drug Administration Schedule; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D007262:Infusions, Intravenous; D007930:Leucine / Q000008:administration & dosage / Q000097:blood / Q000187:drug effects; D008297:Male; D009124:Muscle Proteins / Q000187:drug effects* / Q000378:metabolism*; D019888:Nelfinavir / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D013997:Time Factors; D019562:Viral Load / Q000379:methods
D002247:Carbon Isotopes; D017320:HIV Protease Inhibitors; D009124:Muscle Proteins; D007930:Leucine; D019888:Nelfinavir