{"id":1640,"date":"2009-06-03T09:16:38","date_gmt":"2009-06-03T09:16:38","guid":{"rendered":"http:\/\/localhost.localdomain\/wpmu\/htb\/?p=1640"},"modified":"2013-08-16T13:46:05","modified_gmt":"2013-08-16T13:46:05","slug":"double-dose-lopinavirritonavir-provides-insufficient-lopinavir-exposure-in-children-receiving-rifampicin","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/1640","title":{"rendered":"Double-dose lopinavir\/ritonavir provides insufficient lopinavir exposure in children receiving rifampicin"},"content":{"rendered":"

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

Rifampicin-based TB treatment is recommended for children (there is no formulation of rifabutin for young children nor is it widely available). In South Africa children with HIV who are <3 years old receive lopinavir\/ritonavir-based antiretroviral 1st line regimens. Rifampicin reduces trough concentrations of lopinavir by more than 90%. Additional boosting with ritonavir to a 1:1 ratio during TB treatment provides adequate concentrations in adults and children but this strategy is complex with oral solutions and not always feasible.<\/strong><\/p>\n

Helen McIlleron from the University of Cape Town presented findings from a pharmacokinetic (PK) study using double dose lopinavir\/r (LPV\/r) (ratio 4:1) with rifampicin in young children who were >6 months of age. This strategy has achieved adequate concentrations in healthy adult volunteers.<\/p>\n

In this study, children with TB\/HIV (n=17), received 460\/115mg\/m2 LPV\/r +2NRTIs, once established on rifampicin-based TB treatment. Children without TB (n=24) were used as a control group and received the standard dose LPV\/r 230\/57.5mg\/m2 +2 NRTIs.<\/p>\n

Table 1. Baseline characteristics and PK of children receiving LPV\/r<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n
<\/th>\nTB\/HIV n=17<\/th>\nControls n=24<\/th>\np-value<\/th>\n<\/tr>\n
Male\/female<\/td>\n4\/13<\/td>\n16\/8<\/td>\n0.007<\/td>\n<\/tr>\n
Age (months)<\/td>\n15.0 (12.4-24.9)<\/td>\n19.1 (13.8-26.8)<\/td>\n0.615<\/td>\n<\/tr>\n
Weight (kg)<\/td>\n8.64 (7.02-9.96)<\/td>\n10.55 (8.38 -12.55)<\/td>\n0.007<\/td>\n<\/tr>\n
Cpre (mg\/L)<\/td>\n0.76 (0.17-1.62)<\/td>\n4.25 (3.42-8.10)<\/td>\n0.0001<\/td>\n<\/tr>\n
Cmax (mg\/L)<\/td>\n4.45 (2.51-8.22)<\/td>\n7.94 (6.86-13.40)<\/td>\n0.008<\/td>\n<\/tr>\n
AUC0-8h (mg.h\/L)<\/td>\n22.29 (13.03-47.30)<\/td>\n45.15 (37.25-81.38)<\/td>\n0.010<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Baseline characteristics and PK parameters are median (IQR).<\/p>\n

Pre-dose sampling was performed at 2, 4, and 8 hours after dose and determined using LC-MSMS method.<\/p>\n

Following an interim analysis and DSMB review of plasma levels in 15 children with TB\/HIV the study was stopped.<\/p>\n

The investigators reported a median (IQR) LPV dose of 486 mg\/m2 (478-497) in cases and 234 mg\/m2 (228-241) in controls.<\/p>\n

Characteristics and PK of the children are shown in Table 1. There were more girls than boys with TB\/HIV and children with TB weighed less than controls.<\/p>\n

They noted that among a subgroup of 5 cases sampled 12 hours after the observed dose 12-hour LPV concentrations were 0.65 mg\/L lower than Cpre showing that adherence to the previous dose is unlikely to be the reason for the low concentrations.<\/p>\n

The investigators found high interpatient variability within both groups of children. The median LPV Cpre, Cmax and AUC0-8h were reduced by 82%, 44% and 51% respectively among children receiving double dose LPV\/r with rifampicin-based TB treatment; 10(59%) had subtherapeutic LPV\/r Cpre (<1mg\/L) vs 2 (8%) controls.<\/p>\n

They do not recommend this approach in young children and Dr McIlleron concluded: \u0093There is an urgent need to establish safe, effective and feasible co-treatment for young children with HIV associated tuberculosis\u0094.<\/p>\n

Comment<\/h3>\n

These data are important to offer guidance for \u0093what not to do\u0094 in this population. They also argue for easier to use solid paediatric formulations of LPV\/r and RTV.<\/strong><\/p>\n

Reference:<\/p>\n

McIlleron et al. Double-dose lopinavir\/ritonavir provides insufficient lopinavir exposure in children receiving rifampicin-based anti-TB treatment. 16th CROI. February 2009, Montreal. Oral abstract 98.
\nhttp:\/\/www.retroconference.org\/2009\/Abstracts\/34615.htm<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

Polly Clayden HIV i-Base Rifampicin-based TB treatment is recommended for children (there is no formulation of rifabutin for young children nor is it widely available). In South Africa children with HIV who are <3 years old receive lopinavir\/ritonavir-based antiretroviral 1st …<\/p>\n","protected":false},"author":4,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,32,37],"tags":[63],"class_list":["post-1640","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-paediatric-care","category-tb-coinfection","tag-croi-2009"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/1640","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\/4"}],"replies":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/comments?post=1640"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/1640\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=1640"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=1640"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=1640"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}