Host genetic factors are important in disease progression in children

Numerous host genetic factors play an important role in HIV disease progression in children, according to a report by researchers at the University of California, San Diego, La Jolla, California.

The authors believe their study of more than 1,000 US children represents the largest cohort of children perinatally infected with HIV-1 who have been evaluated for the impact that host genetics has on disease progression and neurocognitive impairment. It is an avenue of research that should lead to treatments being more closely tailored to individual needs.

Genetic factors have an impact on the susceptibility to HIV infection and the rate of progression to AIDS and death and on neurological impairment, the authors explain in the 15 November 2003 issue of The Journal of Infectious Diseases.

Stephen Spector and colleagues evaluated the effects of polymorphisms in CCR2, CCR5, and SDF1 in 1,049 children with symptomatic HIV-1 infection. They found higher mean CD4 lymphocyte counts and percentages, lower mean HIV-1 RNA levels, and higher mean cognitive-index scores in subjects with the CCR5-delta32 allele than in children not bearing this allele.

The researchers looked at children homozygous for wild-type CCR5, and found that 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. These polymorphisms, as well as those in CCR2, were not found to influence disease progression or neurological impairment.

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 strongest single predictor of disease progression among children with wild-type CCR5 was the CCR5-59029 genotype.

In their discussion the authors conclude: “Perhaps the greatest potential that research such as that presented in the present study has is to help guide treatment of HIV-1 infected individuals. As data accumulate regarding both host and virus genetic factors that have an impact on disease progression and neurological impairment, the potential exists that treatment can be individualised for each patient, thereby ensuring that optimal treatment is provided. In this regard, other genetic factors, including HLA types and polymorphisms that impact drug metabolism, also must be assessed, to determine the risk of disease progression and to optimise antiretroviral treatment. In combination, host and virus genetic data promise to provide important information for guiding the future clinical management of HIV-1 infected patients.“

Spector S, Singh K, Barroga C et al Genetic influence of CCR5, CCR2, and SDF1 variants on Human Immunodeficiency Virus 1 (HIV-1) related disease progression and neurological impairment, in children with symptomatic HIV-1 infection. J Infect Dis 2003;188:1461-1472.