December 17, 2010

Types Of White Blood Cells Might Explain Immunity In Children Who Survive HIV Without Treatment

It is a mystery why some children with HIV infection do not get sick.

Researchers from The HIV Netherlands Australia Thailand Research Collaboration at the Thai Red Cross AIDS in Bangkok, the National Center for HIV/AIDS, Dermatology and STD in Phnom Penh and Baylor College of Medicine in Houston think that it might be explained by the types of white blood cells the children have.

Long-term, non-progressors

HIV kills white blood cells that help fight infections. Without treatment, most children become sick and more than one-third die from HIV by age 5. Experts call those who are still healthy without treatment at age 8 "long-term non-progressors."

Such children are uncommon, but these researchers found 50 long-term non-progessor children among 222 children between the ages of 1 and 12 who had HIV and took part in a study in Thailand and Cambodia. None of the children had ever taken anti-HIV medicines.

Unique pattern of white blood cells

When researchers tested their blood cells, they found these long-term non-progressors had a unique pattern of white blood cells. As compared to children who demonstrated HIV disease progression in this study, long-term non-progressor children had higher values of infection-fighting helper T cells, cytotoxic T cells, naïve T cells that encounter new virus, and memory T cells already committed to protection against HIV.

Surprisingly, long-term non-progressors also had elevations of activated helper and cytotoxic T cells, cells that have been associated with advanced HIV disease. One United States study followed 137 children with HIV for more than eight years "“ 10 of them were long-term non-progressors who had fewer activated T cells at a young age. This factor seems to predict who would become a long-term non-progressor.

"This study is the first in Asian children that clearly shows how HIV damages the immune system," said Dr. Jintanat Ananworanich, deputy director in scientific affairs at HIV-NAT and the leader of this study. This is important because the type of HIV found in Asians is usually different from that in Western children and this study confirms a pattern of immune damage that is true across HIV types. How the immune system evolves over time with and without HIV treatment is not well studied. This study is following children for three years to find out what happens to the different white blood cell types after successful treatment.

"We will gain important information from this study on whether treatment makes the immune system return to the normal level seen in children without HIV," said Dr. Mean Chhi Vun, director of the National Center for HIV/AIDS, Dermatology and STD in Phnom Penh.

Customizing treatment

Why is this important? What if a blood test could distinguish between the child who needs life-long HIV medications and the child who can wait for treatment or may not need it at all? This would be a great contribution to the children, their families and the scientific community.

Giving several medications to a child on-time, every single day of his or her life is a difficult and stressful task. Presently, we have very crude measurements of the immune system that tells us which child is likely to fall seriously ill from HIV. This is not ideal and by far too late.

"This study is one of the largest to discern the white blood cell types found in the so-called long-term non-progressors. These children are unique and it is important we find out why," said Dr. William T. Shearer, professor of pediatrics and immunology at Baylor College of Medicine and a senior author of the study.

Longitudinal phase

Longer follow up of children with HIV will be needed to find out why some children handle the HIV differently than others.

"The longitudinal phase of our study will help us identify cell types in the blood that are important for HIV control. If we can find why certain children can control HIV from destroying their immune system, it will be a great achievement," said Dr. Kiat Ruxrungtham, professor of medicine at Chulalongkorn University, Bangkok and deputy director of HIV-NAT.

This study was done at seven Thai centers in seven provinces (Bangkok, Nonthaburi, Khon Kaen, Chiang Rai, Chiang Mai, Chantaburi, Chonburi) and two Cambodian centers in Phnom Penh.

Funding for this work came from the National Institute of Allergy and Infectious diseases and the Thai Research Council.


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