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HLA-Bw4 identifies a population of HIV-infected patients with an increased capacity to control viral replication after structured treatment interruption
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
ID
2832678
Author(s)
Stern, M; Czaja, K; Rauch, A; Rickenbach, M; Günthard, H F; Battegay, M; Fellay, J; Hirschel, B; Hess, C; Swiss HIV Cohort Study Group
HLA-Bw4 identifies a population of HIV-infected patients with an increased capacity to control viral replication after structured treatment interruption
Journal
HIV medicine
Volume
13
Number
10
Pages / Article-Number
589-95
Keywords
HIV-1, human leucocyte antigen (HLA), natural killer cells
Abstract
OBJECTIVES: After structured treatment interruption (STI) of treatment for HIV-1, a fraction of patients maintain suppressed viral loads. Prospective identification of such patients might improve HIV-1 treatment, if selected patients are offered STI. METHODS: We analysed the effect of previously identified genetic modulators of HIV-1 disease progression on patients' ability to suppress viral replication after STI. Polymorphisms in the genes killer cell immunoglobulin-like receptor 3DLI (KIR3DL1)/KIR3DS1, human leucocyte antigen B (HLA-B) and HLA Complex P5 (HCP5), and a polymorphism affecting HLA-C surface expression were analysed in 130 Swiss HIV Cohort Study patients undergoing STI. Genotypes were correlated with viral load levels after STI. RESULTS: We observed a statistically significant reduction in viral load after STI in carriers of HLA-B alleles containing either the Bw480Thr or the Bw480Ile epitope (mean adjusted effect on post-STI viral load: -0.82 log HIV-1 RNA copies/ml, P < 0.001; and -1.12 log copies/ml, P < 0.001, respectively). No significant effects were detected for the other polymorphisms analysed. The likelihood of being able to control HIV-1 replication using a prespecified cut-off (viral load increase < 1000 copies/ml) increased from 39% in Bw4-negative patients to 53% in patients carrying Bw4-80Thr, and to 65% in patients carrying Bw4-80Ile (P = 0.02). CONCLUSIONS: These data establish a significant impact of HLA-Bw4 on the control of viral replication after STI.
