HIV-1-Infected Long-Term Slow Progressors Heterozygous for Δ32-CCR5 Show Significantly Lower Plasma Viral Load Than Wild-Type Slow Progressors

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Abstract
Objective: Patients heterozygous for δ32-CCR5 may have a delayed progression of HIV-1 disease. The aim of the present study was to investigate the influence of CCR5/δ32-CCR5 genotype in long-term slow progressors using plasma viral load as a marker of disease progression. Design: We analyzed 70 long-term slow progressors (diagnosis >8 years previously; CD4 count >500/μl; 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 fluoresence-activated cell sorter (FACS) analysis. The Mann-Whitney-Wilcoxon test was used for statistical analyses. Results: The frequency of the CCR5/δ32-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/δ32-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/Δ32-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.