A phase II/III randomised, open-label study of combination antiretroviral regimens and treatment-switching strategies in HIV-1 infected antiretroviral naïve children >30 days and <18 years of age.
What is the best combination of anti-HIV drugs for children who are starting therapy for the first time? And when should they switch to different combinations?
What was this study about?
PENPACT 1 was a study for children with HIV infection who needed to start treatment for the first time. It had two main aims:
- To compare different combinations of anti-HIV drugs to see which is the best to start with in order to slow the growth of the HIV virus in the body, and to see which has the least side-effects for children.
- To decide what to do if the HIV level rises again in the blood. This trial looked at whether it was better to change to a new set of anti-HIV drugs as soon as the virus becomes detectable, or if it was better to wait until the amount of virus in the blood was a bit higher (but not very high).
What difference did this study make?
Overall, the study found that children had good long-term outcomes on all the treatments strategies. Waiting to change treatment using one kind of drug (protease inhibitors) could be a reasonable where future drug options were limited, because the risk of selecting for resistance on these regimens was low.
Compared with when they started treatment, 4 years later children had average reductions in viral load of 3.16 log copies per mL if they were taking regimens containing protease inhibitors compared with 3.31 log copies per mL if they were taking regimens containing the other type of drug, called non-nucleoside reverse transcriptase inhibitors. This difference was compatible with chance. Those who were changing drugs as soon as the virus became detectable had average reductions in viral load of 3.26 log copies per mL compared with 3.20 log copies per mL for those changing drugs at at higher viral load levels. This difference was also compatible with chance. Protease inhibitor resistance was rare and there was no increase in resistance to other drugs in the regimen in children taking protease inhibitors and changing drugs as soon as the virus became detectable compared with those changing at slightly higher levels. In contrast, resistance to non-nucleoside reverse transcriptase inhibitors was selected early, and about 10% more children accumulated mutations to other drugs in the regimen in those changing drugs at higher levels of virus compared with those changing as soon as the virus became detectable. Of all the 266 children in the trial, only nine (3%) children had new AIDS-like events and 60 (23%) had severe adverse events, similarly numbers in all the randomised groups
Type of study
Who funded the study?
In Europe the trial was funded by PENTA (EU funded) and a number of countries provided local support. In the UK the trial was funded by the Medical Research Council. Sites in the USA and South America were funded by the American NIAID and NICHD.
When did it take place?
The first child was randomised on 25 September 2002 and the last child on 7th September 2005. All children were followed in the trial until September 2009 (a minimum of 4 years).
Where did it take place?
Children were enrolled from countries in Europe and North and South America.
Who was included?
Children with HIV infection who were at least 30 days old and less than 18 years of age who had not had previous treatment with anti-HIV drugs. A total of 266 children took part in this trial.