Prognostic value of a CCR5 defective allele in pediatric HIV-1 infection.
BACKGROUND
A deletion of 32 base pairs in the CCR5 gene (delta32 CCR5) has been linked to resistance to HIV-1 infection in exposed adults and to the delay of disease progression in infected adults.


METHODS
To determine the role of delta32 CCR5 in disease progression of HIV-1 infected children born to seropositive mothers, we studied a polymerase chain reaction in 301 HIV-1 infected, 262 HIV-1 exposed-uninfected and 47 HIV-1 unexposed-uninfected children of Spanish and Italian origin. Infected children were further divided into two groups according to their rate of HIV-1 disease progression: rapid progressors who developed severe clinical and/or immunological conditions within the second year of life, and delayed progressors with any other evolution of disease. Among the latter were the long-term, non-progressors (LTNP) who presented with mild or no symptoms of HIV-1 infection above 8 years of age. Viral phenotype was studied for 45 delayed progressors.


RESULTS
No correlation was found between delta32 CCR5 and mother-to-child transmission of HIV-1. However, the frequency of the deletion was substantially higher in LTNP, compared with delayed (p = 0.019) and rapid progressors (p = 0.0003). In children carrying the delta32 CCRS mutation, the presence of MT-2 tropic virus isolate was associated with a severe immune suppression (p = 0.028); whereas, the presence of MT-2 negative viruses correlated with LTNP (p = 0.010).


CONCLUSIONS
Given the rapidity and simplicity of the assay, the delta32 CCR5 mutation may be a useful predictive marker to identify children with delayed disease progression who, consequently, may not require immediate antiretroviral treatment.
Romiti
M L
ML
Division of Immunology and Infectious Diseases, Children's Hospital Bambino Gesù, University of Rome Tor Vergata, Italy.
Colognesi
C
C
Cancrini
C
C
Mas
A
A
Berrino
M
M
Salvatori
F
F
Orlandi
P
P
Jansson
M
M
Palomba
E
E
Plebani
A
A
Bertran
J M
JM
Hernandez
M
M
de Martino
M
M
Amoroso
A
A
Tovo
P A
PA
Rossi
P
P
Espanol
T
T
Scarlatti
G
G
D000293:Adolescent; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D015658:HIV Infections / Q000235:genetics*; D020276:HIV Long-Term Survivors; D015497:HIV-1; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D019169:Jurkat Cells / Q000821:virology; D008264:Macrophages / Q000821:virology; D009154:Mutation; D010641:Phenotype; D011237:Predictive Value of Tests; D011379:Prognosis; D019713:Receptors, CCR5 / Q000235:genetics*; D017384:Sequence Deletion
D019713:Receptors, CCR5