We studied the influence of
AIDS restriction genes (ARGs) CCR5-Delta32, CCR2-64I,
SDF1-3'A, IL10-5'A, CX3CR1-V249I, CX3CR1-T280M, and MDR1-C3435T and haplotypes of the CCR5 P1 promoter and
RANTES variants -403A, In1.1C, 3'222C, and -28G among HIV-1 infected patients on
highly active antiretroviral therapy (
HAART) in the Multicenter
AIDS Cohort Study (MACS) and the Multicenter
Hemophilia Cohort Study (MHCS). Our results indicate that several ARGs also influence
therapy efficacy (ie, the success in viral suppression) and subsequent progression to
AIDS while on
HAART. CCR5-Delta32 decreased time to viral suppression (<200 HIV
RNA copies/mL, relative hazard [RH]=1.40; P=0.008) and was protective against
AIDS (RH=0.11; P=or<0.0001), whereas the CCR5 P1 haplotype was associated with delayed viral suppression (
RNA<50 copies/mL, odds ratio [OR]=0.65; P=0.03) and accelerated time to
AIDS (RH=2.68; P=0.02).
SDF1-3'A reduced viral suppression (OR=0.61; P=0.02) and accelerated
AIDS (RH=3.18; P=0.009). Accelerated
AIDS progression was also observed with the
RANTES haplotype carrying RANTES-IN1.1C and RANTES-3'222C (P=0.005 to 0.007). In contrast, the
RANTES haplotype H1, which lacks suspected deleterious single-nucleotide polymorphisms, was protective against
AIDS. CX3CR1-V249I seemed to accelerate viral suppression (
RNA<50 copies/mL, OR=1.27; P=0.01). ARG influence after
HAART suggests residual HIV-1 replication, and spread continues even in patients successfully suppressing detectable
viral RNA.