{"id":33859,"date":"2018-04-16T08:35:57","date_gmt":"2018-04-16T08:35:57","guid":{"rendered":"http:\/\/i-base.info\/htb\/?p=33859"},"modified":"2018-04-16T13:30:48","modified_gmt":"2018-04-16T13:30:48","slug":"doubling-raltegravir-dose-might-overcome-interaction-with-rifampicin-in-children-aged-2-to-6","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/33859","title":{"rendered":"Doubling raltegravir dose could overcome interaction with rifampicin in children aged 2 to 6"},"content":{"rendered":"

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

Doubling the dose of raltegravir for children aged two to six years with TB and HIV co-infection who were taking rifampicin achieved adequate concentrations and was found to be safe. Results from IMPAACT P1101 were presented at CROI 2018<\/strong>.<\/p>\n

A dose of 12 mg\/kg of raltegravir (RAL) can be used for TB-HIV co-infected children taking rifampicin in this age group.<\/p>\n

IMPAACT P1101 is a phase 1\/2 dose finding study of RAL for HIV positive children receiving rifampicin (RIF)-containing TB treatment for at least one week. The study has three age cohorts: cohort 1: 2 to <6 years (results shown here), cohort 2: 6 to <12 years of age and cohort 3: 4 weeks to <2 years. Each cohort needs 12 participants for pharmacokinetic (PK) and safety evaluations.<\/p>\n

Participants start a three-drug ART regimen at enrolment, including chewable RAL formulation at 12 mg\/kg\/dose twice daily (twice the recommended paediatric dose).<\/p>\n

Intensive RAL PK sampling is performed one week after ART is started and then a forth ARV is added to the regimen \u2013 standard of care with TB treatment, usually efavirenz or lopinavir\/ritonavir.<\/p>\n

RAL is stopped when TB treatment is completed and participants followed for a further three months. PK targets are a geometric mean (GM) AUC12h of 6\u201320 mgxh\/L (14\u201345 uMxh) and GM C12h ><\/u> 33 ng\/mL (><\/u>75 nM). The study defines virologic success as at least 1 log10 copies\/mL reduction from baseline or viral load <<\/u>400 copies\/mL at week 8.<\/p>\n

The 12 participants were 7 (58%) male, 100% black and median age of 3 years (IQR: 2 to 5). Median baseline viral load 4.91 log10 copies\/mL (IQR: 4.42 to 5.42), CD4 count 559 cells\/mL (IQR: 390 to 1185) and CD4 per cent 15% (IQR 9\u201324). Median follow up was 33 weeks (IQR: 28 to 37). The majority of participants (11\/12) received efavirenz as the forth drug and one participant received lopinavir\/ritonavir.<\/p>\n

At week 1 GM AUC12h was 12.8 mgxh\/L (28.8 uMxh; CV 50%) and GM C12h was 102 ng\/mL (230 nM; CV 76%).<\/p>\n

Median CD4 change from baseline was 101cells\/mm3 and 6.1%.<\/p>\n

One participant had grade 3 AST and grade 3 ALT elevations at week 4 judged possibly related to RAL. RAL\/ART was temporarily stopped for 21 days and then restarted, with no recurrence.<\/p>\n

At week 8 11\/12 (92%) participants achieved virologic success and 9\/12 (75%) viral load <50 copies\/mL; 10\/11 remained <400 copies\/mL through week 24. The participant who did not achieve virologic success was the same one that stopped ART temporarily.<\/p>\n

comment<\/h3>\n

These data are welcome as options for treating coinfected children are scarce. <\/strong><\/p>\n

Results from cohorts 2 and 3 are needed before the double dose of RAL can be recommended for all TB-HIV co-infected infants and children treated with rifampicin. <\/strong><\/p>\n

Reference<\/p>\n

Myers T et al. P1101: phase I\/II study of raltegravir containing regimen in HIV-TB cotreated children. 25th Conference on Retroviruses and Opportunistic Infections (CROI 2018), 4\u20137 March 2018, Boston. Poster abstract 845.
\nhttp:\/\/www.croiconference.org\/sessions\/p1101-phaseiii-study-raltegravir-containing-regimen-hiv-tb-cotreated-children<\/a> (abstract and poster)<\/p>\n","protected":false},"excerpt":{"rendered":"

Polly Clayden, HIV i-Base Doubling the dose of raltegravir for children aged two to six years with TB and HIV co-infection who were taking rifampicin achieved adequate concentrations and was found to be safe. Results from IMPAACT P1101 were presented …<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,32,34,37],"tags":[251],"class_list":["post-33859","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-paediatric-care","category-pk-and-drug-interactions","category-tb-coinfection","tag-croi-2018"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/33859","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=33859"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/33859\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=33859"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=33859"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=33859"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}