HIV-1-INFECTED LONG-TERM SLOW PROGRESSORS HETEROZYGOUS FOR DELTA-32-CCR5 SHOW SIGNIFICANTLY LOWER PLASMA VIRAL LOAD THAN WILD-TYPE SLOW PROGRESSORS

Objective: Patients heterozygous for Delta 32-CCR5 may have a delayed progression of HIV-1 disease. The aim of the present study was to inve stigate the influence of CCR5/Delta 32-CCR5 genotype in long-term slow progressors using plasma viral load as a marker of disease progressio n. Design: We analyzed 70 long-term slow progressors (diagnosis >8 yea rs previously; CD4 count >500/mu l; asymptomatic, never received antir etroviral therapy) for CCR5 genotype, plasma viral load, and lymphocyt e subsets. Distribution of CCR5 genotypes was compared with a cohort o f 61 multiply exposed noninfected individuals and a group of 336 contr ol subjects. All study participants were white. Methods: CCR5 genotype was determined by polymerase chain reaction (PCR) amplification. Plas ma viral load was quantified by branch DNA hybridization, lymphocyte s ubsets were determined by fluoresence-activated cell sorter (FACS) ana lysis. The Mann-Whitney-Wilcoxon test was used for statistical analyse s. Results: The frequency of the CCR5/Delta 32-CCR5 heterozygote genot ype was higher in long-term slow progressors (37.1%) and multiply expo sed noninfected individuals (26.2%, compared with the control group (1 5.8%). In addition, plasma viral load was found to be significantly lo wer in CCR5/Delta 32-CCR5 heterozygous long-term slow progressors (med ian < log(10) 2.70; 53.8% < log(10) 2.70; 0% > log(10) 4.0) relative t o that seen in CCR5/CCR5 long-term slow progressors (median log(10) 3. 64; 22.7% < log(10) 2.70; 22.7% > log(10) 4.0). Conclusions: These fin dings strengthen the hypothesis of a favorable influence of CCR5/Delta 32-CCR5 genotype on progression of HIV-1 infection. Therefore, evalua tion of CCR5 genotype might influence antiretroviral therapy strategie s in early stages of HIV-1 infection.