NEW YORK (Reuters Health) - In children, CCR5 genotype and other host genetic factors play an important role in HIV-related disease progression and neurological impairment, according to a report in the November 15th issue of The Journal of Infectious Diseases.
Numerous host genetic factors have an impact on both the susceptibility to HIV infection and the rate of progression to AIDS and death, the authors explain.
Dr. Stephen A. Spector from University of California, San Diego, La Jolla, California and colleagues evaluated the effects of polymorphisms in CCR2, CCR5, and SDF1 on the rate of disease progression and neurological impairment in 1049 children with symptomatic HIV-1 infection.
Children with the CCR5-delta32 allele, previously linked to protection from HIV infection, had higher mean CD4 lymphocyte counts and percentages, lower mean HIV-1 RNA levels, and higher mean cognitive-index scores than did children not bearing this allele, the authors report.
Among children homozygous for wild-type CCR5, mean lymphocyte percentages and mean cognitive-index scores were higher in those with the CCR5-59353-C/C and mean lymphocyte percentages were higher with the CCR5-59356-T/T genotypes, the report indicates.
These polymorphisms, as well as those in CCR2, were not found to influence disease progression or the decline in neurocognitive status.
In contrast, the researchers note, the A/A genotype of SDF1-3' was associated with a doubling of the relative hazard for disease progression and with a significant increase in neurocognitive impairment associated with disease progression.
In a multivariate analysis, the CCR5-59029 genotype was the strongest single predictor of disease progression among children with wild-type CCR5.
“Specific polymorphisms in an individual child’s genes can significantly impact on how that child will respond to HIV infection and be an important determinant of how rapidly their disease will progress,” Dr. Spector told Reuters Health.
“At this point, children should not be tested for CCR5 polymorphisms,” Dr. Spector said. “However, the time may come that combined with other tests for specific polymorphisms that this can provide useful information in making treatment decisions.”
“We believe that this impact of host genetics on infectious diseases of children is not isolated to HIV but applies to most other infections,” Dr. Spector added. “For example, it is not just luck that one child gets infected with measles virus and recovers in 4 days and another child gets infected with measles virus, develops encephalitis and dies. We believe that there is a predictable host-virus interaction that can be found that can predict these outcomes.”
Source: J Infect Dis 2003;188:1461-1472. [ Google search on this article ]
MeSH Headings:Pathologic Processes: Pathological Conditions, Signs and Symptoms: Disease Progression: Disease Attributes: DiseasesCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
