A randomized controlled trial of genotypic HIV drug resistance testing in HIV-1-infected children: the PERA (PENTA 8) trial.
OBJECTIVE
To evaluate the longer-term utility of genotypic resistance testing in HIV-1-infected children with virological failure.


METHODS
Children aged 3 months-18 years switching antiretroviral therapy (ART) with HIV-1 RNA > 2,000 copies/ml were randomized between genotypic testing (Virtual Phenotype) and no testing at baseline and subsequent virological failures. Children were followed to at least 96 weeks.


RESULTS
One hundred and seventy eligible children, from 24 clinical centres in six countries, were randomized to resistance testing (n = 87) or no testing (n = 83) between June 2000-July 2003. At baseline, mean HIV-1 RNA and CD4+ T-cell percentage were 4.7 log10 copies/ml and 20%, respectively. Children had taken ART for a mean of 5 years; 24% had received all three classes, 53% nucleoside reverse transcriptase inhibitors (NRTIs)+protease inhibitors (PIs), 9% NRTIs+non-nucleoside reverse transcriptase inhibitors (NNRTIs) and 14% NRTIs only. There was no difference between the arms in the drug classes or the individual PIs/NNRTIs prescribed. However, 49% in the resistance test arm (RT) versus 19% in the no-test arm (NT) continued at least one NRTI from their failing regimen; 56% versus 19% were prescribed didanosine+stavudine as their NRTI backbone. Adjusting for baseline HIV-1 RNA, mean reductions in HIV-1 RNA at 48 weeks were 1.51 log10 copies/ml in the RT arm and 1.23 in the NT arm (P = 0.3); the difference between the arms was smaller at week 96 (RT: 1.50, NT: 1.47; P = 0.9).


CONCLUSIONS
In this first paediatric trial of resistance testing, we observed a substantial difference in NRTI-prescribing behaviour across arms. However statistically significant evidence of a long-term virological or immunological benefit was not observed. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN14367816.
Green
Hannah
H
MRC Clinical Trials Unit, London, UK. hannah.green@ctu.mrc.ac.uk
Gibb
Diana M
DM
Compagnucci
Alexandra
A
Giacomet
Vania
V
de Rossi
Anita
A
Harper
Lynda
L
Saïdi
Yacine
Y
Castelli-Gattinara
Guido
G
Pillay
Deenan
D
Babiker
Abdel G
AG
Aboulker
Jean-Pierre
JP
Lyall
Hermione
H
Bacheler
Lee T
LT
Walker
A Sarah
AS
Debré
Marianne
M
Rosso
Raffaella
R
Burger
David M
DM
Della Negra
Marinella
M
Dunn
David T
DT
Giaquinto
Carlo
C
D000293:Adolescent; D044966:Anti-Retroviral Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D001938:Brazil; D002648:Child; D002675:Child, Preschool; D024882:Drug Resistance, Viral; D005060:Europe; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D013045:Species Specificity; D016896:Treatment Outcome
D044966:Anti-Retroviral Agents