No difference in outcomes for children initiating treatment with a protease inhibitor or an NNRTI nor with viral load switching strategies in PENPACT-1

In an oral late breaker, Ann Melvin presented data on behalf of the PENPACT 1 study (a collaboration between PENTA and PACTG/IMPAACT). This was a long-term comparison of antiretroviral naive children initiating treatment on PI or NNRTI based regimens as well as two different viral load criteria for switching from first to second line treatment (>1000 vs 30,000 copies/mL).

This was a randomised study with a 2×2 factorial design. Children in PENPACT 1 received an initial regimen of two NRTIs plus either an NNRTI or a PI and the second randomisation compared switch to second-line at the two different viral load measurements. The primary outcome was viral load change between baseline and 4 years. The minimum follow up was 4 years.

Children were randomised between September 2002 and September 2005 and 263/266 included in the analysis. At the end of the study in August 2009, 218 (83%) children were still in follow up. The median length was 5 years (IQR 4.2-6.0 years).

At baseline, the children were a median age of 6.5 years (IQR 2.8-12.9), CD4 17% (IQR 10-25%), viral load 5.1(4.5-5.7) log10copies/mL. Only 15% had received antiretrovirals for prevention of mother to child transmission and 4% (10/239) had one or more major mutation.

Choice of antiretrovirals within the randomised arm was open label. Lopinavir/r (49%) and nelfinavir (48%) were the most common PIs and efavirenz (61%)the most common NNRTI.

At the end of follow up the majority of children (188/263, 71%) were on their first line regimen. There was no difference between PI (73%) and NNRTI (70%). The median viral load at switch was 6720 copies/mL (IQR 1,380-26,100) compared to 35,712 copies/mL (IQR 8,060-72,800), p<0.01 in the 1000 copies/mL and 30,000 copies/mL switch groups respectively. Children with the higher viral load criterion switched approximately one year later (p=0.04).

The investigators observed no significant differences in change in viral load between baseline and 4 years between children initiating treatment on a PI or NNRTI: -3.16 vs -3.31 log10 copies/mL, giving a difference of -0.15 (95% CI, 0.41-0.11), p=0.26; or children switching earlier or later: -3.26 vs-3.20, difference 0.06 (95% CI, 0.2-0.32), p=0.56.

Similar proportions of children (>70% all groups) had viral load <50 copies/mL and CD4 percentage increase of approximately 16%.

Overall, one child died at week 277 from a malignancy and there were 14 new CDC stage C events in 9 children (3 PI/1000; 3 PI/30,000; 1 NNRTI/1000; 2 NNRTI/30,000). Grade 3 or 4 adverse events occurred in 60 children (28 PI; 32 NNRTI. 30 1000; 30 30,000) of which 17 had their regimen modified.

There were a low number of children for which resistance testing could be performed but preliminary results showed more children with 3 NRTI mutations or more in the NNRTI/30,000 copies/mL group. The most frequent being the M184V.

Dr Melvin suggested that these results are reassuring for paediatric treatment scale up worldwide and, in the absence of nevirapine exposure through PMTCT, either PI or NNRTI are equally good options for first line regimens. She added that although routine viral load testing may help identify children at risk of developing NRTI resistance it is unlikely to have an impact on the acquisition of NNRTI resistance as this occurs soon after viral rebound.

comment

As Dr Melvin remarked, these data are extremely useful for paediatric treatment programmes worldwide.

Ref: Melvin A et al. 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. 18th IAS Conference, 1823 July 2010, Vienna. Oral abstract. THLBB104
http://pag.aids2010.org/Abstracts.aspx?SID=644&AID=17536