HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 DISEASE PROGRESSION, CCR5 GENOTYPE, AND SPECIFIC IMMUNE-RESPONSES

The correlation among the presence of a 32-bp deletion in the CC-chemo kine receptor 5 (CCR5) gene, disease progression, and human immunodefi ciency virus type 1 (HIV-1)-specific immune responses was analyzed for a cohort of 79 Caucasian HIV-1-infected patients. The CCR5 genotype ( CCR5/CCR5 = wild type/wild type or Delta 32CCR5/CCR5 = 32-bp deletion/ wild type) in peripheral blood mononuclear cells was determined by PCR , followed by sequencing of both wild-type and Delta 32CCR5 gene fragm ents. HIV-1-specific humoral responses to gp41 and V3(MN) peptides wer e determined by enzyme immunoassays. The prevalence of the Delta 32CCR 5 allele was lower among 37 patients with rapid progression (progressi on to AIDS or to a CD4 cell count of <200 x 10(6)/liter in less than 9 years; P < 0.01) compared to that for 42 patients with slow progressi on (no AIDS and CD4 cell count of >200 x 10(6)/liter after at least 9 years from infection) or to that for 25 non-HIV-1-infected Swedish blo od donors (P < 0.05). No differences were observed in the wild-type CC R5 sequences between the different groups of patients. For three analy zed patients, the 32-bp Delta 32CCR5 gene deletions were identical. Th e antibody titers against gp41 and a V3(MN) peptide in patients with t he Delta 32CCR5/CCR5 genotype were not significantly different from th ose in pair-matched CCR5/CCR5 controls. However, in 13 analyzed patien ts, a stronger serum neutralizing activity was associated with the Del ta 32CCR5/CCR5 genotype, Thus, a CCR5/CCR5 genotype correlates with a shortened AIDS-free HIV-1 infection period and possibly with a worse n eutralizing activity, without an evident influence on the antibody res ponse to two major antigenic regions of HIV-1 envelope.