{"id":28061,"date":"2015-03-24T09:17:37","date_gmt":"2015-03-24T09:17:37","guid":{"rendered":"http:\/\/i-base.info\/htb\/?p=28061"},"modified":"2015-03-24T11:20:01","modified_gmt":"2015-03-24T11:20:01","slug":"long-term-safety-and-efficacy-of-tenofovir-in-children","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/28061","title":{"rendered":"Long-term safety and efficacy of tenofovir in children"},"content":{"rendered":"

Polly Clayden, HIV i-Base<\/strong><\/p>\n

\"CROI<\/a>Tenofovir was well tolerated in children for up to 336 weeks, according to preliminary efficacy and safety data presented at CROI 2015.<\/strong><\/p>\n

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.<\/p>\n

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.<\/p>\n

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.<\/p>\n

The median duration of TDF was 302 weeks; 79 participants received TDF in OLE extensions; and 48 participants completed 336 weeks.<\/p>\n

At week 336, 80% of participants had viral load <50 copies\/mL, see Table 1.<\/p>\n\n\n\n\n\n\n\n\n\n\n\n
Table1: Virologic response rates in all TDF group by visit OLE (missing=failure)<\/caption>\n
Week<\/th>\nParticipants with viral load <50 copies\/mL<\/th>\n<\/tr>\n
n ( %)<\/td>\n95% CI<\/td>\n<\/tr>\n
48<\/td>\n61\/89 (68.5)<\/td>\n57.8 – 78.0<\/td>\n<\/tr>\n
96<\/td>\n57\/79 (72.2)<\/td>\n60.9 – 81.7<\/td>\n<\/tr>\n
144<\/td>\n54\/78 (68.2)<\/td>\n57.8 – 79.2<\/td>\n<\/tr>\n
192<\/td>\n53\/74 (71.6)<\/td>\n59.9 – 81.5<\/td>\n<\/tr>\n
240<\/td>\n51\/71 (71.8)<\/td>\n59.9 – 81.9<\/td>\n<\/tr>\n
288<\/td>\n45\/64 (70.3)<\/td>\n57.6 – 81.1<\/td>\n<\/tr>\n
336<\/td>\n32\/40 (80.0)<\/td>\n64.4 – 90.9<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

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).<\/p>\n

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.<\/p>\n

One participant developed K65R at week 4 (suggesting it might be archived from previous treatment).<\/p>\n

Reference:<\/p>\n

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.
\nAbstract:
\nhttp:\/\/www.croiconference.org\/sessions\/efficacy-and-safety-long-term-tenofovir-df-tdf-therapy-hiv-infected-children<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

Polly Clayden, HIV i-Base Tenofovir 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 …<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,32],"tags":[203],"class_list":["post-28061","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-paediatric-care","tag-croi-2015"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/28061","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/comments?post=28061"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/28061\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=28061"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=28061"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=28061"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}