Currently Recruiting PENTA 1 |
Currently RecruitingPENTA 15: This study will assess the pharmacokinetics, feasibility and acceptability of dosing ABC or ABC in combination with 3TC once daily in children aged 3 months to <36 months. It is a cross-over, open-label pharmacokinetic multi-centre study. Eligible children are those who have been taking ABC
bid with or without 3TC bid for at least 12 weeks as part of an antiretroviral
regimen and:
In Follow UpPENPACT 1: 266 children have been enrolled in this randomised trial with a factorial design (2x2) to compare
PENPACT 1 is a collaboration between the PENTA network
and the Pediatric AIDS Clinical Trials Group (PACTG) in the USA. The primary
endpoint will be HIV viral load at 4 years after randomisation. The substudy
will look prospectively at the development of lipodystrophy and metabolic
abnormalities in children enrolled in PENTA studies. PENTA 11: a randomised
Phase II trial to determine whether children are disadvantaged clinically,
immunologically or virologically by Planned Treatment Interruptions.
This pilot study is for chronically infected children aged 2 - 15 years
of age, with suppressed HIV viral load and: A PK substudy will look at the best way of stopping NNRTIs. Initial results
were presented at the 2006 XVI World AIDS conference in Toronto .(.pdf
file) PENTA 7: 20 children have been enrolled in an open study to evaluate the toxicity, tolerability and antiviral activity of early d4T+ddI+Nelfinavir (NFV) therapy in HIV infected infants less than 3 months of age. Following the results of PK studies performed on the first infants enrolled, the dose of NFV for very young infants was increased to 150mg/kg/day. 1 child died of non-HIV causes at week 60. 72 week results were published in AIDS. Data at 3 years has shown:
Resistance and adherence studies are also underway to better understand
the virological failures.
Previous Trials PENTA 1: between
1992 and 1995 192 children were enrolled in a randomised trial to evaluate
the benefit of starting ZDV while still asymptomatic or mildly symptomatic. PENTA 3 was originally designed as a randomised trial to evaluate the toxicity and tolerability of ZDV+ddC compared with ZDV as initial therapy in symptomatic HIV infected children. 33 children were randomised, however after the release of results from the Delta trial in adults showing a benefit in starting with combination therapy, all children on ZDV monotherapy switched to ZDV+ddC. A further 37 children were enrolled into an open study with all children receiving ZDV+ddC. The drugs were well tolerated and no untoward toxicity was found. PENTA 4: 162 HIV-1 infected children on stable therapy with ZDV, ZDV+ddI or ddC or ddI alone were randomised to receive lamivudine (3TC) syrup or tablets or matching placebo in addition . In this population of children with relatively advanced HIV disease, the addition of lamivudine to current NTRI therapy was safe and well-tolerated. There was evidence that treatment changes in HIV-1 RNA viral load were greater in children taking regimens which included ZDV. A resistance substudy showed that development of mutation at codon 184 appeared to be slower than seen in similar adult trials suggesting a lower virus turnover, despite the generally high loads seen at baseline (mean 4.9log10 copies/ml). PENTA 5: 128 children were enrolled in a randomised trial to evaluate the antiviral effect of combinations of NRTIs (3TC+Abacavir, 3TC+ZDV, Abacavir+ZDV) and the tolerability of adding NFV. 3 year follow-up data were presented at CROI 2003. Data showed that improved efficacy (in terms of HIV-1 RNA suppression and growth changes) and lower rates of switching with detectable HIV-1 RNA in the 3TC+ABC group were sustained from 48 to 160 weeks. Clinical evidence of lipodystrophy was reported in only 2 (2%) children. There were a number of PENTA 5 substudies:
PERA (PENTA 8): a randomised trial to evaluate the usefulness of resistance testing in the clinical management of children with HIV infection. Children randomised in the resistance testing arm have access to repeat resistance testing in the case of subsequent failure. 171 children were enrolled and followed to 96 weeks. Results of this first paediatric trial of resistance testing were published in Antiviral Therapy. In summary:
PENTA 13 : 24 HIV infected children aged 2-13 were enrolled in a one arm, open label cross-over study to compare the plasma pharmacokinetics of twice daily versus once daily 3TC and Abacavir. The AUC0-24 and Cmax of abacavir given 16mg/kg po q24h and of lamivudine given 8 mg/kg po q24h were not inferior to q12h dosing. Virological data did not indicate a marked difference in antiviral activity between q12h and q24h regimens. Results were published in Antiviral therapy. (.pdf file) PENTA 14:
This was a randomised trial of differing levels of Therapeutic
Drug Monitoring (TDM) compared with no TDM in children with
HIV infection starting or switching to a new antiretroviral regimen. Unfortunately
the trial was stopped due to poor recruitment. A prospective cohort of
children receiving TDM is being planned as it is still important to get
better data on drug levels in the paediatric population. PS For the curious: PENTA 2, 6 and 10 never got off the drawing board! |
Updated
29 February, 2008