PENPACT 1 was a long-term trial run in collaboration between PENTA and PATCG/IMPAACT that studied which 1st line antiretroviral treatment (ART) children should start with, and when children should switch to 2nd line ART.
In total, 263 children were randomised, 131 to start with protease inhibitor (PI) based ART and 132 to start with non-nucleoside reverse transcriptase (NNRTI) based ART. Children were also randomised to either switch to 2nd line ART if their viral load increased to 1,000 copies/ml on 1st line treatment (134 children), or to wait until the viral load increased to 30,000 copies/ml before switching (129 children).
Overall, these children had excellent response to treatment over a median of 5 years, and nearly three-quarters were still on 1st line ART at the end of the study. Children in the 30,000 group switched to 2nd line ART about a year later than those in the 1,000 group, resulting in fewer treatment switches in the high viral switch group (23 vs 37 children).
The main result, measured at 4 years after starting treatment, was that there was no difference in viral response when comparing starting with PI or NNRTI based ART, OR when comparing switching at 1,000 or 30,000 copies/ml.
In addition, staying on 1st line treatment for an additional year did not result in any difference in PI or NNRTI resistance which was similar in the early and late switching groups. However, there was evidence that children on NNRTI based ART were more likely to develop resistance to the NRTI drugs (nucleoside reverse transcriptase inhibitors) if they were in the 30,000 compared to the 1,000 viral load switch group. This was not the case for PI based ART.
Children gained CD4 cells throughout the study and very few had disease progression (no difference between groups). There were also no differences in the number of children experiencing side-effects on PI or NNRTI drugs.
In summary, children in this trial taking ART for the first time had excellent results. If children have not been exposed to an NNRTI to reduce mother-to-child transmission of HIV infection, then either PI or NNRTI are equally good choices for 1st line treatment. Although routine viral load testing may help identify children at risk of developing NRTI resistance, it is unlikely to affect NNRTI resistance because this occurs as soon as viral load becomes detectable.
For HIV infected children worldwide, the PENPACT 1 trial sends a powerful message to start and continue those requiring treatment on ART.
The PENPACT 1 substudy will look prospectively at the development of lipodystrophy and metabolic abnormalities in children enrolled in Penta studies.
The following are copies of letters to families who took part informing them of the trial results: