Early ART treatment dramatically reduces deaths in babies with HIV
Thursday 20 November 2008
Testing infants at risk of HIV as soon as possible, and treating those infected with the virus immediately, dramatically enhances their chances of survival and reduces the likelihood of devastating disease progression in their early life. These results, published this week in the New England Journal of Medicine, have led to changes in international guidelines for the treatment of HIV-infected babies.
An international study based in South Africa and involving UK scientists from the Medical Research Council (MRC) Clinical Trials Unit has shown that administering antiretroviral therapy (ART) to infants immediately after diagnosis, rather than waiting for their CD4 counts to drop or other symptoms to prompt treatment, reduced their chance of dying by 76% (from 16% to 4%) . It also reduced the chance of their disease progressing measurably by 75% (from 26% to 6%). The findings were so conclusive that after review of the preliminary data, all the babies in the trial were re-assessed for ART.
At the onset of the trial, 377 HIV-positive infants were enrolled aged between six and 12 weeks. These were a special group of children as most of them had contracted HIV despite measures taken to avoid mother-to-child transmission. It stands to reason a number of them were infected in utero. They were randomly allocated to one of three arms in the study, called the Children with HIV Early Antiretroviral Therapy (CHER) Trial.
One arm received treatment in line with then current WHO guidelines. This means the babies were only treated with ART when their CD 4 count fell (below 25% for infants, below 20% for toddlers – over 12 months old) or other clinical symptoms emerged. Of this group, 66% had received ART by the time of their 40 week follow-up.
The other two arms received early ART: half of the children until the age of one and the other half until the age of two. The trial is still ongoing and final results as to which of these two groups does better long-term will further inform the treatment of infants with HIV.
Professor Diana Gibb, senior paediatrician and clinical trials specialist, and Professor Abdel Babiker, senior statistician, both from the MRC Clinical Trials Unit collaborated with the South African team on the study.
Professor Gibb explains: “We did not expect to see differences so soon between the infants receiving early treatment and those in the group where treatment started only when immunity was falling or symptoms developed. The trial was designed to explore whether an early ‘blast’ of ART could help these HIV-infected babies get through early difficulties when their immune systems are still developing. The main aim of CHER was to see if treating early for a limited period would have long-term benefits.”
Dr Avy Violari and Professor Mark Cotton, from the Comprehensive International Program of Research on AIDS (CIPRA-SA) sponsored by the National Institutes of Health (NIH), were the principal investigators running the trial in Johannesburg and Cape Town.
Dr Violari, based at the Perinatal HIV Research Unit at the University of Witwatersrand, Johannesburg, says: “Our results reinforce the view that there are no reliable predictors for small infants as to how their disease is progressing. CD4 counts do not tell us with enough accuracy if babies under a year of age are becoming sick. What was alarming was the speed of disease progression; some infants could seem fine in the morning and get sick and die by nightfall. Some did not even make it to the hospital. When these early data were analysed, it became clear that treating all infants at the earliest opportunity after diagnosis was the best course of action.
Professor Cotton said: “We are delighted that our study in South Africa has led to changes in WHO guidelines and that immediate treatment is now recommended wherever possible. It is to be hoped that this will save countless babies across the world, especially in low-income countries where mother-to-child transmission is still common. However, in order to start ART early, it is important to undertake HIV viral diagnosis very early in life which does require a programme with both manpower and resources.”
Professor Gibb said: “We look forward to the full results of the trial to see how these children fare long-term. Clearly avoiding mother-to-child transmission in the first place must remain the top priority. These drug regimens are no picnic for these babies and even with improved outcomes in early life, there is still no cure for AIDS.”
As well as the change in the WHO policy, guidelines governing the treatment of infants with HIV have been altered to reflect the recommendations of the CHER trial both in Europe and in the United States.
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Notes:
- The “Children with HIV Early Antiretroviral Therapy” (CHER) study is the largest Phase III randomized clinical trial to study strategies of giving antiretroviral therapy in very young infants, including the best time to begin ART in infants. Launched in South Africa in July 2005, CHER is sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, USA. The study was conducted at the Perinatal HIV Research Unit of the University of the Witwatersrand and at the Children’s Infectious Diseases Clinical Research Unit of Tygerberg Children’s Hospital and Stellenbosch University, as part of CIPRA-SA, in collaboration with the Medical Research Council Clinical Trials Unit, London, UK. GlaxoSmithKline plc (United Kingdom) and the South African Department of Health provided drugs.
- Avy Violari, Mark F. Cotton, Diana M. Gibb, Abdel G. Babiker, Jan Steyn, Shabir A. Madhi, Patrick Jean-Philippe, and James A. McIntyre for the CHER Study Team. Early Antiretroviral Therapy and Mortality among HIV-Infected Infants. New England Journal of Medicine (2008): 359;21. www.nejm.org November 20, 2008.
- The study was conducted at the Perinatal HIV Research Unit of the University of the Witwatersrand in Soweto (www.phru.co.za) and at the Children’s Infectious Diseases Clinical Research Unit of Tygerberg Children’s Hospital and Stellenbosch University, (www.kidcru.org.za), in collaboration with researchers at the Medical Research Council Clinical Trials Unit, London, UK, as part of the CIPRA-SA collaboration (www.cipra-sa.com).
- The CIPRA-SA collaboration is one of the largest international NIH funded HIV research efforts, including researchers from the Universities of the Witwatersrand, Stellenbosch and Cape Town and the National Health Laboratory Services.
