CHEMOKINE RECEPTOR POLYMORPHISM AND AUTOLOGOUS NEUTRALIZING ANTIBODY-RESPONSE IN LONG-TERM HIV-1 INFECTION

We have previously reported that slowly progressing HIV infection (SPI ) was associated with the presence of contemporaneous autologous neutr alizing anti-bodies. In contrast, a group of individuals with more rap idly progressing infection (RPI) generally lacked these antibodies. To understand the importance of autologous neutralizing antibodies in SP I more fully, we have now conducted a prospective study taking consecu tive blood samples from the individuals with SPI (8 patients) and RPI (10 patients). Blood sampling in the group with SPI was done 110 and 1 23 months after the estimated seroconversion and at similar time point s in the group with RPI. Virus isolation was attempted at both time po ints in both groups of individuals; crossed neutralization assays were set up with autologous virus. These confirmed our previous finding of significant autologous neutralizing titers in the group with SPI (geo metric mean titer [GMT] 8.7 versus 1.6 in SPI and RPI, respectively; p = 0.0048). However, not all individuals with SPI possessed autologous neutralizing antibody titers did not increase from early to late seru m samples. Finally, late virus isolates from individuals with SPI gene rally remained sensitive to neutralization by early serum samples. Vir us phenotype (SI/NSI) and CCR5 genotype was determined for all individ uals.Neither showed significant correlation with SPI. However, all SPI individuals who were heterozygous for the CCR5 deletion were infected with virus of NSI phenotype. In contrast, all RPI individuals who wer e heterozygous for the CCR5 deletion were infected with virus SI pheno type (p = .028). Thus, a beneficial effect of having a partly nonfunct ional CCR5 coreceptor may depend on the viral SI/NSI phenotype.