Update on New Antiretrovirals for Children and Adolescents
An oral suspension of fosamprenavir/ritonavir (FPV/r) was also approved in the U.S. earlier this year in April for use in children 4 weeks to less than 6 years of age.
Jorg Sievers presented data from the APV20002 study that looked at PK, safety and antiviral activity of FPV/r twice daily in PI-naive and PI-experienced children 4 weeks to <2 years of age. This evaluation was across two age cohorts: cohort 1, 6 months to <2 years and cohort 2, 4 weeks to <6 months of age.
APV20002 was a phase 2, open label, multicentre study in which Intensive pharmacokinetic sampling was performed at 2 or 8 weeks and pre-dose samples were collected every 4-12 weeks. Safety and viral load were monitored every 4-12 weeks.
The older cohort was dosed at 45/7 mg/kg FPV/r twice daily and the younger 45/10 mg/kg twice daily.
Overall 54 children were included in the intent-to-treat-exposed analysis (28 in cohort 1 and 26 in cohort 2). At baseline the children were a median age of 6 months (range 2 - 24), with a median viral load of 5.6 log10 copies/mL (range 5 - 6.15) and CD4 percentage of 26% (range 18 - 34).
At 48 weeks, the median exposure to FPV/r was 640 days (range 8-1093), with 78% exposed >48 weeks and 50% >96 weeks.
When the investigators compared plasma amprenavir (APV) AUC0-t to historical adult data, the geometric mean ratios were 0.744 (90% CI 0.542 - 0.957) and 0.720 (90% CI 0.568 - 0.975) in cohort 1 and 2 respectively. For the Ct these values were, 1.00 (90% CI 0.833 - 1.21) and 0.397 90.298 - 0.528).
Despite lower Ct in the younger cohort, antiviral response was similar across the age groups: 64% percent of children in cohort 1 and 58% in cohort 2 achieved viral load < 50 copies/mL at 48 weeks. The median increase in CD4 percentage was 5% in both cohorts.
The most common AEs were diarrhoea (54%), gastroenteritis (36%) and upper respiratory tract infection (36%). Drug-related grade 2-4 AEs occurred in 20% of children, most frequently increased blood chlolesterol (10%) and gastroenteritis (3%). Twenty-two children experienced serious AEs, three were considered to be drug-related. Three children died following serious AEs including one two month old boy with traditional (herbal) medicine poisoning.
Although somewhat opaque in their approach, the EMA are expected to follow suit with these approvals in the not too distant future. More details on these drugs and others under investigation for children can be read in our paediatric antiretroviral pipeline report.
Links to other websites are current at date of posting but not maintained.
Pediatrics Studies at 19th International AIDS Conference and the 4th International Workshop on HIV Pediatrics
This article was provided by HIV i-Base. It is a part of the publication HIV Treatment Bulletin. Visit HIV i-Base's website to find out more about their activities, publications and services.
Add Your Comment:
(Please note: Your name and comment will be public, and may even show up in
Internet search results. Be careful when providing personal information! Before
adding your comment, please read TheBody.com's Comment Policy.)
The content on this page is free of advertiser influence and was produced by our editorial team. See our content and advertising policies.