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Background:  The virologic, immunologic, and metabolic effects of switching components of a successful HAART have not yet been investigated in HIV-infected children. We assessed the strategy of replacing protease inhibitor (PI) by efavirenz (EFV) and stavudine (d4T) by tenofovir (TDF) in HIV-infected children with long-lasting viral suppression.

Methods:  We randomized 27 HIV-infected children (age range 5.0 to 17.5 years) with HIV RNA < 50 copies/mL for the last 48 weeks, on HAART containing lamivudine (3TC) + d4T+ 1 PI to switch d4T to TDF and PI to EFV at baseline (n = 14; group A) or at week 24 (n = 13; group B). All HIV-infected children maintained 3TC and were followed with clinical assessment, HIV RNA, CD4 count, fasting metabolic, and renal parameters for 48 weeks. Changes of the study variables have been analyzed by analysis of variance for repeated measures.

Results:  From baseline to week 24 and at week 48, groups A and B showed:  unchanged CD4 count (884, 759, 848 vs 809, 795, 754 cells/µL); HIV RNA < 50 copies/mL; unchanged and normal levels of serum creatinine, phosphate, calculated creatinine clearance; absence of proteinuria and glycosuria. Group A, from baseline to week 24, showed a significant decrease on total cholesterol (–20%; p < 0.03), triglycerides (–35%; p < 0.05) and total cholesterol/HDL ratio from 3.5 to 3.0; p < 0.006); and at week 48, we observed stable cholesterol levels and a further decrease of triglycerides and HDL cholesterol. Group A children with elevated (> 95th percentile for age and sex) cholesterol and triglyceride levels showed a marked decrease of both variables over the study period (from 43 to 0% and from 36 to 7%, respectively). Group B, from baseline to week 24, showed unchanged cholesterol, triglycerides, HDL cholesterol and percentage of HIV with elevated cholesterol and triglyceride levels; at week 48, we observed a significant decrease of cholesterol (–14%; p < 0.03), triglycerides (–41%; p < 0.05), and HDL cholesterol (from 3.9 to 3.2; p < 0.006). Group B children with elevated cholesterol and triglyceride levels showed marked reduction of both variables after the initiation of the new regimen (from 46 to 8% and from 54 to 0%, respectively). No adverse effects occurred through the study.

Conclusions:  In HIV-infected children, switching from 3TC/d4T/PI to 3TC/TDF/EFV is safe both virologically and immunologically, well tolerated, and not associated with signs of nephrotoxicity, and leads to a significant improvement of lipid profile and reversion of lipid abnormalities.

Keywords: Pediatric HIV-infection; Swiching study; metabolic abnormalities