{"id":1159,"date":"2009-02-18T22:22:19","date_gmt":"2009-02-18T22:22:19","guid":{"rendered":"http:\/\/localhost\/new\/htb\/?p=1159"},"modified":"2017-02-11T02:43:17","modified_gmt":"2017-02-11T02:43:17","slug":"dosing-of-lopinavirritonavir-in-the-chips-cohort","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/1159","title":{"rendered":"Dosing of lopinavir\/ritonavir in the CHIPS cohort"},"content":{"rendered":"

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

Sarah Walker from the Medical Research Council presented data from the UK\/Irish Collaborative HIV Paediatric Study (CHIPS) cohort looking at paediatric dosing of lopinavir\/ritonavir (LPV\/r).<\/strong> [1]<\/p>\n

Dr Walker explained that the licensed LPV\/r paediatric daily dose is 460 mg\/m2<\/sup> without, and 600 mg\/m2 with concomitant NNRTI therapy. The 460 mg\/m2<\/sup> dose without NNRTIs was chosen in preference to 600 mg\/m2<\/sup> in a post hoc drug-interaction analysis [2]. Following the completion of the phase II trial, this post hoc analysis revealed a significant interaction between NNRTI and LPV\/r, leading to the lower dose being licensed for use without NNRTI. The phase II trial showed very good viral load data overall, with 79% of children <400 copies\/mL at 48 weeks, but this was based on the higher 600 mg\/m2<\/sup> dose. Because of this uncertainty some paediatricians prefer to prescribe the higher dose of LPV\/r irrespective of concomitant NNRTI therapy.<\/p>\n

In the CHIPS study the investigators evaluated the LPV\/r doses prescribed without NNRTIs in the cohort from 2000\u20132007.<\/p>\n

They looked at predictors of current dose, including sex, VL and CD4, age, CDC stage, height\/weight-for-age, calendar year, formulation, frequency and previous PI use, using mixed models allowing child and hospital effects.<\/p>\n

They also evaluated the impact of the LPV\/r dose on viral load suppression 6 months after starting it using logistic models and over longer follow up using binomial mixed models.<\/p>\n

Dr Walker reported, 311\/1,336 (25%) children in the cohort had received LPV\/r without an NNRTI; for a total of 654 child-years. Of these children, 238 (77%) were still on LPV\/r when they were seen last.<\/p>\n

The median age of the children at initiation of LPV\/r was 9 (IQR 5\u201312) years. The investigators recorded 684 doses in 299\/311 children of which 52% were syrup, 38% capsules and 10% tablets. 662 (97%) doses were taken twice daily.<\/p>\n

Overall the dose\/m2<\/sup> could be estimated 2,748 times in 278 children (the remaining children did not have height\/weight recorded). They found few (7%) doses were >10% below the 460 mg\/m2 target, and few (9%) >10% above the 600 mg\/m2 target, with the majority >410\u2013<530 mg\/m2 (46%) or >530\u2013<660 mg\/m2 (39%).<\/p>\n

In a multivariate analysis, the investigators found doses were: 17 mg\/m2<\/sup> [95%CI 0\u201334], higher in children who had prior CDC C event, p=0.05; 2 mg\/m2<\/sup> [0\u20133] higher for every log10 higher VL, p=0.02; 48 mg\/m2<\/sup> [38\u201358] higher with capsules\/tablets vs syrups, p<0.001; 22 mg\/m2<\/sup> [4\u201340] higher with twice- vs once-daily dosing, p=0.02; 19 mg\/m2<\/sup> [15\u201324], p=0.001, and 10 mg\/m2<\/sup> [6\u201314], p<0.001 higher for every one unit lower current weight- and height-for-age, respectively; and 9 mg\/m2<\/sup> [5\u201314] higher for every year younger over 10, p<0.05.<\/p>\n

Dr Walker noted that the mean dose for a 10 year old, without prior CDC event, average weight and age for height receiving capsules or tablets was 546mg\/m2<\/sup>. She also noted that dosing varied greatly by centre with some using higher and some lower doses.<\/p>\n

The investigators found no evidence that the initial LPV\/r dose was associated with significantly improved viral load suppression at 6 months and reported: <400 copies\/mL, AOR=1.06 per 50 mg\/m2<\/sup> (95%CI 0.87-1.28), p=0.58; <50 copies\/mL, AOR=0.81 per 50mg\/m2<\/sup> (95%CI 0.65-1.01), p=0.06.<\/p>\n

The investigators concluded: \u201cDoses were higher with capsules\/tablets, likely reflecting over- rather than under-dosing when solid formulations cannot achieve exact doses. However, we found no clear evidence that higher doses improved VL suppression.\u201d<\/p>\n

Dr Walker added: \u201cOpinion seems to be split as to the most appropriate LPV\/r dose in children.\u201d<\/p>\n

References:<\/p>\n

    \n
  1. Walker AS et al. To overdose or underdose? The question of Kaletra in children in the UK\/Irish Collaborative HIV Paediatric Study (CHIPS). 9th International Congress on Drug Therapy in HIV Infection , Glasgow. November 2008. Abstract O123.
    \nhttp:\/\/www.jiasociety.org\/content\/11\/S1\/O8<\/a><\/li>\n
  2. Saez-Llorens X, et al.: Forty-eight-week evaluation of lopinavir\/ritonavir, a new protease inhibitor, in human immunodeficiency virus-infected children. Pediatr Infect Dis J 2003, 22:216-224.<\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

    Polly Clayden, HIV i-Base Sarah Walker from the Medical Research Council presented data from the UK\/Irish Collaborative HIV Paediatric Study (CHIPS) cohort looking at paediatric dosing of lopinavir\/ritonavir (LPV\/r). [1] Dr Walker explained that the licensed LPV\/r paediatric daily dose …<\/p>\n","protected":false},"author":4,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4],"tags":[85],"class_list":["post-1159","post","type-post","status-publish","format-standard","hentry","category-conference-reports","tag-hiv-9-glasgow-2008"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/1159","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=1159"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/1159\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=1159"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=1159"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=1159"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}