{"id":25857,"date":"2014-05-27T12:21:10","date_gmt":"2014-05-27T12:21:10","guid":{"rendered":"http:\/\/i-base.info\/htb\/?p=25857"},"modified":"2014-05-28T08:31:49","modified_gmt":"2014-05-28T08:31:49","slug":"once-daily-lopinavirritonavir-not-recommended-for-routine-use-in-children-and-adolescents","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/25857","title":{"rendered":"Once daily lopinavir\/ritonavir not recommended for routine use in children and adolescents"},"content":{"rendered":"

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

A PENTA trial conducted in Europe, Thailand, Argentina and Brazil did not demonstrate non-inferiority of once-daily to twice-daily lopinavir\/ritonavir in children and adolescents. <\/strong><\/p>\n

Lopinavir\/ritonavir is approved for use in adults once- or twice-daily, but only for twice-daily in children.<\/p>\n

KONCERT was a phase 1\/2 randomised trial in which children and adolescents 18 years or less, weighing at least 15kg, on lopinavir\/ritonavir based ART with suppressed viral load (<50 copies\/mL) for 24 weeks or more, either continued twice-daily dosing or switched to once-daily. Dosing was according to FDA approved body weight-based recommendations.<\/p>\n

Hermione Lyall from Imperial College London presented data from the trial at CROI 2014 on behalf of the KONCERT investigators.<\/p>\n

Participants were followed for minimum of 48 weeks with visits at weeks 0, 4, 8, 12 then every 12 weeks. The primary outcome was the proportion with confirmed viral load >50 copies\/mL at 48 weeks. The non-inferiority margin was 12%.<\/p>\n

A subset (n=53) of participants in the once daily arm had lopinavir\/ritonavir pharmacokinetic (PK) evaluations at baseline (while still on twice daily dosing) and at four weeks (n=26). PK analyses were per-protocol and all others intention-to-treat.<\/p>\n

A total of 173 participants were randomised to lopinavir\/ritonavir either once-daily (n=86) or twice-daily (n=87). They were a median age of 11 years old (range 3.8 to14.7); 18% were aged 3 to 7, 43% 8 to 12 and 39% 13 to 18 years. There was a broad ethnic mix: 25% white, 27% black, 35% Asian, 6% mixed and 6% other. Median CD4 percent was 33% overall but there were more participants in the twice daily arm with CD4 percent above 30% (67% vs 60%).<\/p>\n

At randomisation there was viral rebound in five children in the once-daily arm (none in the twice-daily). Median viral load was 120 copies\/mL (range 51 to 91201) vs 134.5 copies\/mL (range 57 to 270) in the once- and twice-daily arms respectively.<\/p>\n

Over 50% of participants had been exposed to three classes of drugs and only 20% were on their first antiretroviral regimen.<\/p>\n

The investigators found the AUC 0-24 and C (last) were less for the subset in the PK study at four weeks (once daily) compared to baseline (twice daily), see Table 1.<\/p>\n\n\n\n\n\n
Table 1: AUC0-24 and C(last) with once vs twice-daily<\/caption>\n
<\/td>\nonce-daily (95%CI)<\/th>\ntwice-daily (95% CI)<\/th>\nonce\/twice daily GM ratio (90% CI)<\/th>\n<\/tr>\n
AUC0-24 GM\n

h*mg\/L<\/p><\/th>\n

160.9\n

(138.4 to 187.0)<\/p><\/td>\n

223.9\n

(194.8 to 257.4)<\/p><\/td>\n

0.72\n

(0.61 to 0.85)<\/p><\/td>\n<\/tr>\n

C(last)\n

mg\/L<\/p><\/th>\n

1.03\n

(0.61 to 1.75)<\/p><\/td>\n

5.69\n

(4.58 to 7.07)<\/p><\/td>\n

0.18\n

(0.11 to 0.29)<\/p><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Dr Lyall noted that a C(last) level just above 1 mg\/L is considered to be acceptable and 40% in the study were below that level. She added that only two participants who took part in the PK substudy had viral rebound and both had good trough levels: 6.4 mg\/L and 2.1 mg\/L in the twice- and once-daily arms respectively. This raises the question of whether viral rebound is associated with drug levels or with adherence, she said.<\/p>\n

At 48 weeks 12 vs 7 participants in the once- vs twice-daily arms had confirmed viral load >50 copies\/mL; the estimated difference was 6% (90% CI -14 to 2), p=0.196. Because the confidence interval crossed the 12% level the study did not demonstrate non-inferiority.<\/p>\n

Of the 12 people who had viral rebound at any point in the once-daily arm 7\/9 who remained on the same dosing schedule resuppressed.<\/p>\n

Changes from baseline to week 48 in CD4 percent, CD4 count, biochemistry, hematology, lipids, resistance and adverse events were similar between arms.<\/p>\n

There was a strong preference for once-daily dosing with 84% participants\/carers saying they preferred this. There was no significant difference between arms in adherence.<\/p>\n

Although the results can be partly explained by chance viral load and CD4 percentage imbalances at baseline, they do not support the routine use of once daily lopinavir\/ritonavir in children and adolescents.<\/p>\n

Comment<\/h3>\n

Although these results do not support the routine use of once daily lopinavir\/r in children and adolescents, in settings with close monitoring this might still be an option for a minority.<\/strong><\/p>\n

As with adults, once-daily boosted darunavir and atazanavir are preferred. <\/strong><\/p>\n

Reference:<\/p>\n

Lyall H et al. Final results of Koncert: A randomised noninferiority trial of QD Vs BD LPV\/r dosing in children. 21st CROI. 3-6 March 2014, Boston. Oral abstract 74LB.
\nhttp:\/\/www.croiwebcasts.org\/console\/player\/22148<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

Polly Clayden, HIV i-Base A PENTA trial conducted in Europe, Thailand, Argentina and Brazil did not demonstrate non-inferiority of once-daily to twice-daily lopinavir\/ritonavir in children and adolescents. Lopinavir\/ritonavir is approved for use in adults once- or twice-daily, but only for …<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,3,32],"tags":[187],"class_list":["post-25857","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-antiretrovirals","category-paediatric-care","tag-croi-2014"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/25857","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\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/comments?post=25857"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/25857\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=25857"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=25857"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=25857"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}