Heterozygosity for CCR5-Delta32 but not CCR2b-64I protects against certain intracellular pathogens.
OBJECTIVE
To determine the association between CCR5 and CCR2b genotype and the clinical manifestation of first and subsequent AIDS-defining illnesses (ADIs).


METHODS
The distribution of ADIs was examined by CCR5 and CCR2b genotype in a subset of homosexual men enrolled in the Sydney AIDS Prospective Study. The expected number of ADIs was calculated from rates observed in the same tertiary hospital over the same period.


RESULTS
Information on initial ADI was collected for 117 homosexual men diagnosed with AIDS before January 1998. Of these individuals, 17 were heterozygous for the CCR5-Delta32 mutation and 11 were heterozygous for CCR2b-64I. The number of observed cases of Pneumocystis carinii pneumonia (PCP), toxoplasmosis, Mycobacterium avium complex (MAC) and cryptosporidiosis reported as a first ADI was substantially fewer in people heterozygous for the CCR5-Delta32 mutation than for those without the mutation, despite similar age, CD4 T-cell count at AIDS diagnosis, year of AIDS diagnosis and receipt of antiretroviral treatment. In addition, among individuals heterozygous for CCR5-Delta32 there were fewer cases of PCP, toxoplasmosis, MAC, and cryptosporidiosis observed as subsequent ADIs compared to the number expected, based on rates measured in the same hospital during the same period (seven observed vs. 24 expected, RR = 0.3, 95% CI = 0.01-0.6). The distribution of first and subsequent ADIs did not differ from the number expected in individuals heterozygous for the CCR2b-64I mutation.


CONCLUSIONS
Results from this study show that heterozygosity for CCR5-Delta32 but not CCR2b-64I appears to protect against opportunistic infections.
Ashton
L J
LJ
National Centre in HIV Epidemiology and Clinical Research, University of New South Wales and St Vincent's Hospital, Sydney, Australia. lashton@nchecr.unsw.edu.au
Stewart
G J
GJ
Biti
R
R
Law
M
M
Cooper
D A
DA
Kaldor
J M
JM
D017088:AIDS-Related Opportunistic Infections / Q000235:genetics / Q000517:prevention & control*; D015331:Cohort Studies; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D018451:Homosexuality, Male; D006801:Humans; D008297:Male; D009154:Mutation; D054390:Receptors, CCR2; D019713:Receptors, CCR5 / Q000235:genetics*; D019707:Receptors, Chemokine / Q000235:genetics*
C515334:CCR2 protein, human; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D019707:Receptors, Chemokine