New research findings show that treating infants with HIV early, and then giving them a break from treatment, leads to better results than waiting until they get sicker to start them on treatment. These findings from the CHER trial, which took place in South Africa, were presented at the Conference on Retroviruses and Opportunistic Infections in Seattle on 6th March 2012.
Infants with HIV are at a high risk of dying or their disease getting worse while they are infants. Early treatment with antiretroviral therapy (ART) helps to prevent this. However, treating infants with ART has its own problems: starting children on ART is a lifelong commitment, and costs money. The drugs can have side effects. Their disease may develop resistance to the drugs that are currently available, and the earlier they start treatment the more time there is for resistance to develop.
The CHER (Children with HIV Early antiretroviral) trial was set up to test whether starting infants on treatment early, but then stopping their treatment for a while, could help to reduce these problems. Researchers split 377 HIV-infected children randomly into three groups:
- those who did not start treatment until their disease got worse (standard treatment according to World Health Organisation treatment guidelines at the time), but did not interrupt their treatment once they had started
- those who started treatment straight away and stopped after one year, restarting when their disease got worse
- those who started treatment straight away and stopped after two years, restarting when their disease got worse
Researchers followed up these children for up to six years, to see how well they survived and remained free of disease progression.
The trial found those infants who started ART straight away for one or two years, and then stopped, had better survival by their 5th birthday than those who did not start treatment until later. Children who started ART straight away (between 6 and 12 weeks) for one or two years and then had a break were one third more likely to survive with no worsening of their disease by the end of the study than those who started treatment later. The results also suggest that children who had early ART for two years may be able to have a slightly longer break from treatment and tended to have better health outcomes than those who had early ART for only one year.
Mark Cotton of Stellenbosch University, one of the principal investigators of the trial said:
"These results are very encouraging, as they reinforce the importance of starting infants with HIV on treatment early. Early treatment followed by a break may become an accepted strategy in the future. It is definitely better and more cost-effective than delaying starting infants on treatment."
Di Gibb, professor in epidemiology and investigator for the CHER trial at MRC CTU said:
"The study indicates that if you have limited money for treating children with HIV, starting them on treatment early for the first year or two will save more lives than if you had used the money to treat them continuously but waited until early signs of deterioration before starting."
Abdel Babiker, professor of medical statistics at MRC CTU, and one of the statisticians for the trial said:
"CHER is the first and longest randomised trial assessing practical strategies (that can be implemented in low and middle income countries) for the management of infants with HIV. The encouraging results highlight the importance of rolling out testing for HIV in infancy, so they can be started on treatment early."
Before these results lead to any changes in practice, more information is needed about the effect of treatment breaks on levels of the virus in children’s blood, and resistance to ART. These results should be available from the CHER trial later this year. More details of the current results will be available when they are published in a peer-reviewed journal.
Very early results from the trial have already had an impact across the world, as back in 2008 they led to a change in the World Health Organisation’s guidelines. Instead of waiting until an infant’s diseases gets to a certain level before starting treatment, treating infants immediately was shown to significantly improve survival. This happened largely before any interruption had happened. These new results reinforce the early results but show that early treatment for one or two years and then stopping is better than waiting. They provide encouragement that for some children treatment can be stopped safely for some time, if the child’s health and immune system is monitored well.
Avy Violari of the University of Witwatersrand in South Africa, also a principal investigator on the trial, said:
"The next stage might be to compare early treatment followed by a break with early continuous treatment, to see which strategy is better for children. We also need to find out what the optimum length of initial treatment is. In this trial we looked at one year and two years, and two years seemed better. But it may be that treating children for 3-5 years could lead to an even longer break before they need to go back on treatment for life."
The trial was carried out in Cape Town and Johannesburg in South Africa by the Perinatal HIV Research Unit of the University of Witwatersrand, the Children’s Infectious Disease Clinical Research Unit of Stellenbosch University, and MRC Clinical Trials Unit, London, as part of the CIPRA-SA programme.
The research was funded by the Division of AIDS, NIAID, NIH and drugs were provided by GlaxoSmithKline.