An age-dependent association of mannose-binding lectin-2 genetic variants on HIV-1-related disease in children.

ABSTRACT

BACKGROUND: Mannose-binding lectin (MBL) is part of the lectin pathway of complement activation against various pathogens; however, its role in innate immune responses against HIV-1 infection in children is unknown. OBJECTIVE: This study evaluated the effects of mannose-binding lectin-2 (MBL2) alleles on HIV-1 disease progression and central nervous system (CNS) impairment in children. METHODS: A cohort of 1037 HIV-1-infected children enrolled in Pediatrics AIDS Clinical Trial Group protocols P152 and P300 before the availability of effective antiretroviral therapy was genotyped for MBL2 and evaluated for disease progression. RESULTS: Children with the homozygous variant MBL2-O/O genotype were more likely to experience rapid disease progression and CNS impairment than those with the wild-type AA genotype. The effects were predominantly observed in children younger than 2 years. In unadjusted Cox proportional hazards models, children younger than 2 years with MBL2-O/O experienced more rapid disease progression (O/O vs AA relative hazard [RH], 1.54; 95% CI, 1.07-2.22; P = .02; O/O vs A/O RH, 2.28; 95% CI, 1.09-4.79; P = .029). Similarly, children with MBL2-O/O were more likely to experience rapid progression to CNS impairment (O/O vs A/A RH, 2.78; 95% CI, 1.06-2.69, P = .027; O/O vs A/O RH, 1.69; 95% CI, 1.07-7.21; P = .035). The effects remained significant after adjustment for CD4(+) lymphocyte count, plasma HIV-1 RNA, and other genotypes. CONCLUSIONS: MBL2-O/O genotypes, which result in lower expression of MBL, are associated with more rapid HIV-1-related disease progression, including CNS impairment, predominantly in children younger than 2 years. These data suggest that MBL2 variants are associated with altered HIV-1 disease progression, particularly in young children.