Journal
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
Volume 48, Issue 3, Pages 263-271Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/QAI.0b013e31816fdc5f
Keywords
AIDS; AIDS restriction gene; highly active antiretroviral therapy; single-nucleotide polymorphism
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Funding
- Intramural NIH HHS [Z01 BC005367] Funding Source: Medline
- NCI NIH HHS [N01-CO-12400, N01CO12400] Funding Source: Medline
- NCRR NIH HHS [M01 RR000722, 5-M01-RR-00722] Funding Source: Medline
- NIAID NIH HHS [U01 AI035043, U01-AI-37613, U01 AI035039, U01 AI035041, U01-AI-35040, U01 AI035040, U01-AI-35039, U01-AI-37984, U01 AI035042, U01-AI-35042, U01 AI037984, U01-AI-35041, U01 AI037613, U01-AI-35043] Funding Source: Medline
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We studied the influence of AIDS restriction genes (ARGs) CCR5-Delta 32, CCR2-64I, SDF1-5'A, IL10-5'A, CX3CRI-V249I, CX3CRI-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-Delta 32 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 = <0.0001), whereas the CCR5 PI 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 HI, which lacks suspected deleterious single-nucleotide polymorphisms, was protective against AIDS. CX(3)CR1-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.
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