CCR2 and CCR5 genotypes in HIV type 1-infected adolescents:: Limited contributions to variability in plasma HIV type 1 RNA concentration in the absence of antiretroviral therapy

In HIV-1-infected individuals, plasma viral RNA concentration as well as preservation of CD8(+) naive T cells can vary by age. Host genetic factors previously shown to mediate HIV-1 pathogenesis in adults and children may operate differently in HIV-1-infected adolescents. Our PCR-based haplotyping of genetic variants at the loci encoding CC (beta) chemokine receptor 2 (CCR2) and CCR5 revealed nine haplotypes (designated A through G*2) in 179 seronegative and 228 seropositive adolescent participants from the Reaching for Excellence in Adolescent Care and Health (REACH) Study of the Adolescent Medicine and HIV/AIDS Research Network. The influence of CCR2-CCR5 haplotypes and genotypes on plasma HIV-1 RNA level was assessed in 207 AIDS-free seropositive individuals (mostly African-American females) who either did not receive therapy or had discontinued therapy for 6-12 months during initial follow-up between 1996 and 1999. The CCR2-64I-coding haplotype F*2 and the infrequent CCR5 Delta32-bearing haplotype G*2 had negligible impact on HIV-1 RNA level (p>0.83) and CD4(+) T cell counts (p>0.30). In contrast, nine carriers of the E/E genotype had significantly higher (p=0.007) plasma HIV-1 RNA level and slightly reduced CD4(+) cell counts (p=0.15) compared with those not carrying E/E or F*2 or G*2. The effect of E/E on HIV-1 RNA was stronger (P<0.001) in a multivariable model adjusted for F*2 or G*2 (p=0.45), race (p=0.23), gender (p=0.002), age (p=0.26), and history of antiretroviral therapy (p<0.001). Thus, among the major CCR2-CCR5 haplotypes/genotypes in chronically infected and predominantly African-American adolescents, only the E/E genotype appeared to influence early host-virus equilibration.