SIGNIFICANCE Children with HIV infection often have difficulty maintaining normal weight and decrease weight rapidly when acutely ill. Past studies of adults have suggested that HIV infection is assciated with both increased protein catabolism and that protease inhibitor therapy improves lean body mass(LBM). We hypothesized that HIV-infected children have high rates of proteolysis which decrease following treatment with protease inhibitor therapy.

METHODS Subjects: To date we have studied three young HIV-infected children(2F/1M; age 5 ± 1.3; Race: 2H, 1B, CDC category B). Each child had previously been selected for treatment with the protease inhibitor (PI) Viracept@. Each was studied immediately before beginning treatment with PI and after six weeks of PI therapy, when free of acute superinfection for at least 4 weeks. Three age-matched control volunteers were studied one time each. Proteolysis was measured using the stable isotope [1-13C]leucine (0.35 mg/kg bolus, followed by a constant infusion at 0.65 mg/kg/hr) and mass spectrophotometric analysis. Lean body mass (LBM) was measured by DEXA and resting energy expenditure (REE) was measured by indirect calorimetry.

RESULTS: As estimated from rate of leucine appearance (Ra), proteolysis was significantly higher in HIV subjects than in controls (HIV=182 ± 6, C=112 ± 7 mg/kgLBM/hr; p=0.01). Proteolysis significantly decreased following 6 weeks of PI therapy (Ra: prePI=182 ± 6, 6 wks PI=132± 8 mg/kgLBM/hour; p<0.05). Proteolysis correlated with HIV viral burden (r=0.71). The average increase in LBM after 6 weeks of PI therapy was 0.5 kg. After 6 weeks of PI treatment, REE decreased, but results were not statistically significant (prePI=36 ± 4; postPI=22 ± 6 kjoules/kg/24hrs).

CONCLUSIONS: 1) Proteolysis is higher in HIV-infected children than in controls; 2) Protease inhibitors decrease proteolysis and increase LBM; 3) Proteolysis correlates with HIV viral burden; 4) Protease inhibitors may decrease REE in HIV-infected children.

SPECULATION: 1) Poor weight gain in HIV-infected children is caused by excessive protein catabolism; 2) Protein catabolism may be related to HIV viral burden; 3) Protease inhibitors improve protein catabolism by decreasing proteolysis.