Child in CHER trial has undetectable viral load years after stopping antiretroviral therapy
24 Jul 2017
A nine-year-old South African child who was diagnosed with HIV infection at one month of age and received anti-HIV treatment during infancy has been suppressing the virus without drugs for 8.5 years, scientists reported today at the 9th IAS Conference on HIV Science in Paris.
The child was diagnosed with HIV infection in 2007 at 32 days of age and then enrolled in the Children with HIV Early Antiretroviral Therapy (CHER) randomised controlled trial . At the time the trial started, babies in most countries including South Africa were not given HIV treatment until they were sick or their immune system showed signs of damage, because of concerns about side-effects, drug resistance and cost. HIV-infected infants in the trial were assigned at random to receive either deferred antiretroviral therapy (ART) or early ART for 40 or 96 weeks, then have a break from treatment until there were signs they needed to resume ART. The child was assigned to the group that received early ART for 40 weeks.
Before starting treatment, the child had very high levels of HIV in the blood (viral load), but after beginning ART at nearly 9 weeks of age, treatment suppressed the virus to undetectable levels. Investigators halted treatment after 40 weeks and closely monitored the infant’s immune health, and the child has remained in good health during years of follow-up examinations. Although it was not standard practice in South Africa to monitor viral load in people who were not on ART, recent analyses of stored blood samples taken during follow-up showed that the child maintained an undetectable level of HIV.
When the child was 9.5 years old, researchers conducted thorough laboratory and clinical studies to assess the presence of HIV in and the immune health of the child. The scientists detected a reservoir of virus integrated into a very small proportion of immune cells, but otherwise found no evidence of HIV infection. The child had a healthy level of key immune cells, an undetectable viral load and no symptoms of infection. The researchers detected a trace of immune-system response to the virus, but did not find any HIV capable of replicating. The scientists also confirmed that the child does not have genetic characteristics associated with spontaneous control of HIV, indicating that the 40 weeks of ART provided during infancy were essential to achieving HIV remission.
“To our knowledge, this is the first reported case of sustained control of HIV in a child enrolled in a randomized trial of ART interruption following treatment early in infancy,” said Avy Violari, who co-led the study of the case presented today as well as the CHER trial with Mark Cotton. Dr. Violari is head of pediatric research at the Perinatal HIV Research Unit, part of the University of the Witwatersrand in Johannesburg. Dr Cotton is head of the division of pediatric infectious diseases and director of the family infectious diseases clinical research unit at Stellenbosch University, South Africa.
The researchers believe that other factors, in addition to receiving early ART, were responsible for helping the child keep the virus suppressed. They hope that through studying the child they will learn more about how the immune system can stop HIV replication.
The main results of the CHER trial showed that starting babies on ART early, even for a limited period was better than delaying the start of treatment until the child was sick or their immune system showed signs of damage. These results led to changes in international guidelines to encourage early HIV treatment for babies.
Abdel Babiker, Professor of Epidemiology and Medical Statistics at the MRC CTU at UCL, said,“Were it not for the CHER trial, the ability of this child to control virus post treatment MAY WELL not have been found. Treatment was interrupted per design and the randomisation means that the child was not selected for interruption based on his clinical characteristics”.
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.