{"id":14766,"date":"2011-04-01T13:20:34","date_gmt":"2011-04-01T13:20:34","guid":{"rendered":"http:\/\/i-base.info\/htb\/?p=14766"},"modified":"2011-04-01T13:20:34","modified_gmt":"2011-04-01T13:20:34","slug":"long-term-outcomes-for-infants-starting-lopinavirritonavir-at-less-than-6-months","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/14766","title":{"rendered":"Long-term outcomes for infants starting lopinavir\/ritonavir at less than 6 months"},"content":{"rendered":"

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

World Health Organisation (WHO) and national guidelines recommend universal treatment with antiretrovirals for all HIV-infected infants.<\/p>\n

Guidelines also recommend using protease inhibitor-based treatment for children exposed to single dose nevirapine through PMTCT.<\/p>\n

Initiation of therapy is recommended as soon as possible but there are limited data to guide treatment of very young infants.<\/p>\n

Ellen Chadwick and colleagues from IMPAACT P1030 showed data in AIDS, published ahead of print in February 2011, from a study designed to look at the pharmacokinetics (PK) and safety of the liquid formulation of lopinavir\/ritonavir (LPV\/r) in HIV-infected infants starting treatment between 2 weeks and 6 months of age.<\/p>\n

This was a prospective, open label, phase I\/II study of 31 children from 17 centres in the US and Brazil treated with a high dose (300mg LPV\/75mg RTV\/m2 twice daily). Children were enrolled into two age groups: 14 days to 6 weeks and 6 weeks to <6 months. Children were followed until 48 weeks after the last child was enrolled.<\/p>\n

The median duration of follow up was 123 (range 4-252) weeks. Ten (32%) children permanently discontinued the study including four before 12 months of age. Two discontinued after viral rebound to >50,000 copies\/mL (weeks 43 and 176); three after parents refusal to attend study visits and\/or give medication (weeks 2,42 and 145), three had non-treatment related conditions (CMV resulting in death at week 8; failure to thrive due to severe food allergy at week 70 and severe iron-deficiency anaemia at week 120) and two because their research sites closed (weeks 73 and 120).<\/p>\n

Intensive PK sampling was performed at in 26 children at 12 months of age, pre-dose and 2, 4, 8 and 12 hours after an observed dose. Of these, 20 children had evaluable results.<\/p>\n

The investigators found, the median AUC of the two groups was comparable at 12 months of age (99.1 ug h\/mL [IQR 82.4-124.5] vs 112 ug h\/mL [IQR 95.0-148.8], p=0.93). They also found a significant positive correlation of LPV trough concentration and age, p<0.0001.<\/p>\n

By ITT analysis, at week 48, 22\/31 (71%) children had a viral load <400 copies\/mL; 6\/10 in group 1 and 16\/21 in group 2. Of these 11\/15 (73%) on study treatment at 48 weeks had a viral load <50 copies\/mL. Overall 29\/31 (94%) children achieved a viral load <400 copies\/mL while on study treatment and 19\/29 (66%) children remained undetectable until the end of the study at a median of 123 (range 42-252) weeks. The children who sustained viral suppression had a higher percentage of predose time points at which concentrations exceeded the LPV target of 1 ug\/ML (92 vs 71%), p=0.002.<\/p>\n

The median baseline CD4 percentage was 35% (range 11-59%). There was a median increase of 4% (95% CI – 4 to 13%), p=0.12, among the 24 children with data available at 48 weeks and 23 (96%) had CD4 percentage >25%. Among the 19 children with follow up through 96 weeks there was a median increase of 8% (95% CI -2 to 13%), p=0.15.<\/p>\n

The investigators noted that low LPV levels occurred at two weeks of therapy, with the lowest in infants <6 weeks of age. In this very young age group the median AUC was approximately half that seen in the older children >6 months of age. But these values were comparable between the two groups by 12 months of age and comparable to adults. They also noted that the LPV dose of 300mg\/m2 is higher than the currently recommended dose for children >6 months of age.<\/p>\n

Reference:<\/p>\n

Chadwick EG et al. Long-term outcomes for HIV-infected infants less than 6 months of age at initiation of lopinavir\/ritonavir combination antiretroviral therapy. AIDS, 25(6):767-776 (13 March 2011).
\nhttp:\/\/journals.lww.com\/aidsonline\/toc\/2011\/03130<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

Polly Clayden, HIV i-Base World Health Organisation (WHO) and national guidelines recommend universal treatment with antiretrovirals for all HIV-infected infants. Guidelines also recommend using protease inhibitor-based treatment for children exposed to single dose nevirapine through PMTCT. Initiation of therapy is …<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[32],"tags":[],"class_list":["post-14766","post","type-post","status-publish","format-standard","hentry","category-paediatric-care"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/14766","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=14766"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/14766\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=14766"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=14766"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=14766"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}