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Some HIV patients treated with highly active antiretroviral therapy (HAART) do not resolve their plasma viraemia or HIV RNA can reappear after a period of virological control. We investigate whether polymorphisms in cytokine genes affect the control of plasma HIV RNA over 5 years on HAART.The study utilized adult HIV-infected patients in Western Australia. Plasma HIV-RNA levels were assessed from commencement of HAART in patients who had a CD4 T-cell count less than 100 cells/μl before HAART and achieved immune reconstitution assessed by CD4 T-cell counts.Control of plasma viraemia could be predicted from carriage of allele 2 at position −889 in the IL1A gene (IL1A−889*2). This was significant when assessed by the proportion of patients with a plasma HIV-RNA level of 400 copies/ml or less (P = 0.002). At 48 months post-HAART, proportions were approximately 0.76, 0.51 and 0.32 for IL1A (1,1), (1,2) and (2,2) patients, respectively. The outcome was independent of the patients’ CD4 T-cell counts before or on therapy, drug regimen or age. Polymorphisms in IL6, TNFA, IL1B or IL12B had less significant effects, which became marginal when IL1A was included in the statistical model. IL1A−889 was in linkage disequilibrium with a non-synonymous polymorphism at IL1A+4845.Alleles carried at IL1A−889 or IL1A+4845 may predict the control of HIV replication in previously immunodeficient patients responding to HAART.