Background: Limited long term data are available for pediatric TDF use. We describe preliminary efficacy and safety in HIV-infected children treated with TDF for up to 336 weeks.
Methods: Children ages 2-16 years with HIV-1 RNA <400 copies/mL (c/mL) on a stavudine (d4T)- or zidovudine (ZDV)-containing regimen were randomized to maintain d4T or ZDV or switch to open label (OL) 8 mg/kg TDF oral powder or 300 mg tablets for 48 weeks. Following the randomized phase, subjects in the TDF arm could continue on TDF and those on d4T or ZDV could switch to OL TDF oral powder or tablets at investigator discretion. Subjects maintained their background ARVs for up to 336 weeks in three 96-week study extensions. Safety (adverse events [AE] and laboratories) and efficacy (HIV-1 RNA [Roche Amplicor or Taqman]) were assessed every 12 weeks. Spine and total body less head (TBLH) bone mineral density (BMD) was measured by dual energy X-ray absorptiometry every 24-48 weeks. Proportion with HIV-1 RNA < 50 copies/mL (missing=failure) was assessed. 95% CIs of the point estimate were calculated from the Exact method.
Results: 89 subjects received TDF (49.4% male, median age 7 years, median CD4 1095 cells/mm3, median CD4% 34). Median TDF duration was 302 weeks. 79 subjects received TDF in OL extensions. Seven discontinued OL TDF for AEs (hypophosphatemia [n=2]; proteinuria [n=2]; brain neoplasm, glycosuria, and arthralgia and hypophosphatemia [n=1 each]). TDF adherence was 95% in 45/89 subjects (50.6%). At Week 336, 32/40 subjects (80.0%; 95% CI 64.4, 90.9%) had HIV-1 RNA <50 c/mL. The most frequent AEs were nasopharyngitis (62.9%), dental caries (23.6%), cough and diarrhea (both 21.3%), and gastroenteritis (20.2%). At Week 336, median change from BL in estimated GFR (Schwartz) was -28.7 mL/min/1.73m2 (n = 38, BL 166.6 mL/min/1.73m2) and median BMD percentage change from BL was +43.44% for spine (n=23) and +18.50% for TBLH (n=24). Overall 13/86 subjects (15.1%) had >4% decreases from BL in either spine or TBLH BMD, n=3 at >1 visit.
Conclusions: Most HIV-1 infected children with data available maintained viral responses to TDF-based ARV at Week 336. TDF was well-tolerated. Estimated GFR changes were consistent with increases in age. Few TDF-recipients had persistent BMD decreases. TDF can be considered as a once-daily component of ARV therapy in HIV-infected children.