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 neutralizing antibodies. In contrast, a group of individuals with more rapidly progressing infection (RPI) generally lacked these antibodies. To understand the importance of autologous neutralizing antibodies in SPI more fully, we have now conducted a prospective study taking consecutive blood samples from the individuals with SPI (8 patients) and RPI (10 patients). Blood sampling in the group with SPI was done 110 and 123 months after the estimated seroconversion and at similar time points in the group with RPI. Virus isolation was attempted at both time points 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 (geometric 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 antibodies, indicating that other factors may be decisive for SPI. Furthermore, neutralizing antibody titers did not increase from early to late serum samples. Finally, late virus isolates from individuals with SPI generally remained sensitive to neutralization by early serum samples. Virus phenotype (SI/NSI) and CCR5 genotype was determined for all individuals. 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 were heterozygous for the CCR5 deletion were infected with virus of SI phenotype (p = .028). Thus, a beneficial effect of having a partly nonfunctional CCR5 coreceptor may depend on the viral SI/NSI phenotype.
Schønning
K
K
Department of Infectious Diseases, Hvidovre Hospital, Denmark.
Joost
M
M
Gram
G J
GJ
Machuca
R
R
Nielsen
C
C
Nielsen
J O
JO
Hansen
J E
JE
D018791:CD4 Lymphocyte Count; D018450:Disease Progression; D005838:Genotype; D015483:HIV Antibodies / Q000097:blood; D015658:HIV Infections / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology / Q000502:physiology*; D006579:Heterozygote; D006801:Humans; D009500:Neutralization Tests; D010641:Phenotype; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D019713:Receptors, CCR5 / Q000235:genetics*
D015483:HIV Antibodies; D019713:Receptors, CCR5