Abstract

PENPACT-1 (PENTA 9/PACTG 390): a randomised trial of protease inhibitor (PI) vs non-nucleoside reverse transcriptase inhibitor (NNRTI) combination antiretroviral (ART) regimens and viral load (VL) treatment switching strategies in HIV-1-infected ART-naive children age >30 days and < 18 years

A. Melvin, PENPACT 1 Study Team

University of Washington/Seattle Childrens Hospital, Pediatrics/Infectious Disease, Seattle, United States

Background: Direct comparisons of PI vs NNRTI first-line ART and VL switch criteria have not been studied in children.
Methods: PENPACT-1 assessed long-term effectiveness of initiating 2 NRTIs + PI vs NNRTI ART; a second randomisation compared switch to second-line at VL >1000 vs >30000. The primary outcome was VL change between baseline and 4 years.
Results: 263 children were included (66 PI-1000, 68-NNRTI 1000, 65 PI-30000, 64 NNRTI-30000); median age 6.5(IQR:2.8-12.9) years, mean(SD) CD4 18%(11), VL 5.1(0.8) log₁₀c/ml, and height/weight Z-scores -1.0(1.4)/-0.8(1.5). LPV/r (49%) and NFV (48%) were the most common PIs, EFV (61%) the most common NNRTI. Median follow-up at trial completion was 5.0 (IQR:4.2-6.0) years. At 4 years, no significant differences were observed for mean change in VL, CD4%, height/weight Z-scores or %VL< 400 (Table). Most (188/263, 71%) children were on first-line ART at their last visit. Median VL at switch in the 60 children who started a second-line regimen was significantly higher in 30000 vs 1000 groups per design, but CD4%/count at switch was similar (Table). One child died (NNRTI 1000); new CDC stage C events occurred in 9 (3 PI-1000, 1 NNRTI-1000, 3 PI-30000, 2 NNRTI-30000).

Parameter	N	PI	NNRTI	Difference (95%CI)	P-value	1000 c/ml	30000 c/ml	Difference (95%CI)	P-value
Mean VL change at 4 years (log10c/ml)	233	-3.18	-3.30	-0.12 (-0.38,0.14)	0.35	-3.28	-3.20	0.08 (-0.18,0.34)	0.50
Mean CD4% change at 4 years	221	+13.7	+15.2	1.5 (-0.7,3.7)	0.19	+15.1	+13.9	-1.1 (-3.4,1.1)	0.27
Mean height Z-score change at 4 years	225	+0.61	+0.74	0.13 (-0.09,0.35)	0.27	+0.65	+0.70	0.05 (-0.17,0.27)	0.66
Mean weight Z-score change at 4 years	228	+0.53	+0.77	0.24 (0.00,0.48)	0.05	+0.73	+0.58	-0.15 (-0.39,0.09)	0.21
% VL <400 c/ml at 4 years	233	81%	78%		0.49	81%	78%		0.45
Median VL at switch (c/ml)	60	-	-	-	-	6720	35712	0.93 log10c/ml (0.30,1.15)	0.001
Mean CD4% at switch	60	-	-	-	-	27%	23%	-3.6 (-9.1,2.0)	0.20
Mean CD4 count at switch (cells/mm3)	60	-	-	-	-	1107	739	-368 (-820,83)	0.11

[Summary of results]


Conclusions: There were no significant virologic, immunologic, or clinical differences between any of the randomised groups. Resistance testing is ongoing.