HTB South

Long-term safety and efficacy of tenofovir in children

Polly Clayden, HIV i-Base

CROI logoTenofovir was well tolerated in children for up to 336 weeks, according to preliminary efficacy and safety data presented at CROI 2015.

There are concerns about long-term bone and renal safety among children receiving tenofovir disoproxil fumarate (TDF), for which data are limited. It is approved in children and adolescents age 2 – 18 years in the US and EU. Paediatric formulations (150, 200 and 250 mg tablets and a 40 mg/g powder) are available.

Results from the extension to the GS-US-104-352 study, conducted in the US and Panama, were shown in a poster presentation. GS-US-104-352 was a Phase 3, randomised, open-label, non-inferiority study, comparing the safety of switching d4T or AZT to TDF vs continuing d4T or AZT in children 2 – 16 years of age. At week 48, 40/48 (83.3%) vs 45/49 (91.8%) in the TDF and d4T/AZT arms respectively had viral load <400 copies/mL: difference -8.5 (95% CI: -21.5 to 4.5), p=0.23. All participants who received d4T/AZT in the randomised phase were switched to TDF in the open label extension (OLE) phase.

Overall, 89 participants received TDF: median age 8 years (range 2 -15), 49.4% boys, median CD4 1095 cells/mm3 and median CD4 percent 34%. Twenty-four children were in the 2 – 6 years age group, 59 were 6 – 12, and 6 were 12 years and above.

The median duration of TDF was 302 weeks; 79 participants received TDF in OLE extensions; and 48 participants completed 336 weeks.

At week 336, 80% of participants had viral load <50 copies/mL, see Table 1.

Table1: Virologic response rates in all TDF group by visit OLE (missing=failure)
Week Participants with viral load <50 copies/mL
n ( %) 95% CI
48 61/89 (68.5) 57.8 – 78.0
96 57/79 (72.2) 60.9 – 81.7
144 54/78 (68.2) 57.8 – 79.2
192 53/74 (71.6) 59.9 – 81.5
240 51/71 (71.8) 59.9 – 81.9
288 45/64 (70.3) 57.6 – 81.1
336 32/40 (80.0) 64.4 – 90.9

Nine participants discontinued OLE TDF for adverse events: 3 hypophosphatemia, 2 proteinuria, 2 arthralgia, 1 brain neoplasm and 1 glycosuria. Six discontinuations were related to renal toxicity (hypophosphatemia; proteinuria and glycosuria).

Overall, 13/86 (15.1%) participants had >4% decline in bone mineral density (BMD) in the spine or total body (less head) at one post baseline visit; 3 had >4% decline in BMD at >1 visit. Bone fractures were reported in 3 participants but were trauma-related and none were considered related to study drug.

One participant developed K65R at week 4 (suggesting it might be archived from previous treatment).

Reference:

Saez-Llorens X et al. Efficacy and safety of long-term tenofovir DF (TDF) therapy in HIV-infected children. 2015 CROI, 23-26 February 2015. Poster abstract 954.
Abstract:
http://www.croiconference.org/sessions/efficacy-and-safety-long-term-tenofovir-df-tdf-therapy-hiv-infected-children