Background. Lipoatrophy progresses with increased exposure to an antiretroviral regimen containing lamivudine (3TC) + stavudine (d4T) + protease inhibitor (PI) in HIV-infected children and adolescents (HIV). Switch studies in HIV-infected adults demonstrated an increase in peripheral fat mass and a partial reversion of lipoatrophy  by substitution of d4T with abacavir or tenofovir (TDF). Pediatric data are lacking.

Methods. A prospective study on changes in whole-body composition following substitution of d4T and PI with TDF and efavirenz in 27 HIV (age 5.0-17.9 years; mean BMI 18.8 cm²) successfully treated with 3TC+d4T+1PI (mean exposure 280 weeks).Body composition parameters were measured by Dual-energy X-ray Absorptiometry (DXA); secondary end points included HIV-RNA, CD4⁺ count and percentage. As a control group for DXA data, we studied 143 healthy controls (age 4.9 to 20.0 years ; mean BMI 18.8 cm²).Regression equations for each body composition variable were generated and used to calculate the expected normal values. Comparisons between observed and expected measurements were performed by paired t-test.

Results. Fourteen HIV were followed up to 72 weeks and 13 up to 96 weeks. All HIV maintained virological suppression and unchanged CD4⁺ count and percentage. At baseline, HIV showed decreased total, arms and legs fat masses (p<0.01) and a similar trunk fat mass compared to values computed from HC. At weeks 72-96, HIV showed a significant (p<0.04) mean increase in total fat of 17%, legs fat of 18%, and arms fat of 40%, but unchanged trunk fat, in comparison to baseline.These increases in fat mass were independent from increased adiposity and pubertal changes. Fat mass increments of HIV (from baseline to weeks 72-96) were comparable to those expected for HC (total fat: +1.3 vs. +1.2 Kg, arms fat: +0.09 vs. + 0.08 Kg, legs fat +0.5 vs. 0.5 Kg, trunk fat + 0.6 vs. 0.6 kg). However, at weeks 72-96, total and legs fat mass in HIV were still significantly  lower than those expected in HC (p<0.02). Lean mass in HIV was similar to that expected in HC at baseline as well as at 72-96 weeks.

Conclusions. In lipoatrophic HIV-infected children and adolescents switching from d4T to TDF for 72-96 weeks leads to a significant increase in total and limbs fat, comparable to the physiological expected fat accrual, without any loss of virological control and immunorecovery. Nevertheless, lipoatrophy is still present; thus, additional strategies need to be evaluated.