HIV-1-infected long-term slow progressors heterozygous for delta32-CCR5 show significantly lower plasma viral load than wild-type slow progressors.
OBJECTIVE
Patients heterozygous for delta32-CCR5 may have a delayed progression of HIV-1 disease. The aim of the present study was to investigate the influence of CCR5/delta32-CCR5 genotype in long-term slow progressors using plasma viral load as a marker of disease progression.


METHODS
We analyzed 70 long-term slow progressors (diagnosis > 8 years previously; CD4 count > 500/microl; asymptomatic, never received antiretroviral therapy) for CCR5 genotype, plasma viral load, and lymphocyte subsets. Distribution of CCR5 genotypes was compared with a cohort of 61 multiply exposed noninfected individuals and a group of 336 control subjects. All study participants were white.


METHODS
CCR5 genotype was determined by polymerase chain reaction (PCR) amplification. Plasma viral load was quantified by branch DNA hybridization, lymphocyte subsets were determined by fluorescence-activated cell sorter (FACS) analysis. The Mann-Whitney-Wilcoxon test was used for statistical analyses.


RESULTS
The frequency of the CCR5/delta32-CCR5 heterozygote genotype was higher in long-term slow progressors (37.1%) and multiply exposed noninfected individuals (26.2%), compared with the control group (15.8%). In addition, plasma viral load was found to be significantly lower in CCR5/delta32-CCR5 heterozygous long-term slow progressors (median < log10 2.70; 53.8% < log10 2.70; 0% > log10 4.0) relative to that seen in CCR5/CCR5 long-term slow progressors (median log10 3.64; 22.7% < log10 2.70; 22.7% > log10 4.0).


CONCLUSIONS
These findings strengthen the hypothesis of a favorable influence of CCR5/delta32-CCR5 genotype on progression of HIV-1 infection. Therefore, evaluation of CCR5 genotype might influence antiretroviral therapy strategies in early stages of HIV-1 infection.
Medizinische Poliklinik, Klinikum Innenstadt, Ludwig-Maximilians-Universität München, Germany.
R
R
Walli
B
B
Reinhart
B
B
Luckow
E
E
Lederer
O
O
Loch
A
A
Malo
R
R
Wank
D
D
Schlöndorff
F D
FD
Goebel
D015331:Cohort Studies; D018450:Disease Progression; D005838:Genotype; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology; D015497:HIV-1; D006579:Heterozygote; D006801:Humans; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000166:cytology; D019713:Receptors, CCR5 / Q000235:genetics*; D019562:Viral Load; D014766:Viremia / Q000235:genetics / Q000276:immunology
D019713:Receptors, CCR5