Host Genetic Influences on Highly Active Antiretroviral Therapy Efficacy and AIDS-Free Survival
Year: 2008
Type: article
Abstract: 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.
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Awards: G1224172541, G1356092923, DCTD Computer Support, GENERAL CLINICAL RESEARCH CENTER, G1799052500, G1826418709, G2220614285, G227110230, G2888050928, The Genetic Structure of Natural Populations Past and Present, G403271778, Natural History of AIDS in Homosexual Men, MULTICENTER AIDS COHORT STUDY PATHOGENESIS RESEARCH, University of Pittsburgh Multicenter AIDS Cohort Study (MACS), Center/Coordination, Analysis and Management/MACS, G604406090, MULTICENTER AIDS COHORT STUDY PATHOGENESIS RESEARCH LABS, Multicenter AIDS Cohort Study, G814781356, Multicenter AIDS Cohort Study - Part B (Baltimore Center)
OpenAlex ID: W2050645428