Human immunodeficiency virus type 1 primary isolate neutralization resistance is associated with the syncytium-inducing phenotype and lower CD4 cell counts in subtype CRF01_AE-infected patients

人类免疫缺陷病毒 1 型原发分离株中和抗性与亚型 CRF01_AE 感染患者的合体诱导表型和较低的 CD4 细胞计数有关

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作者:Victoria R Polonis, Mark S de Souza, Janice M Darden, Somsak Chantakulkij, Thippawan Chuenchitra, Sorachai Nitayaphan, Arthur E Brown, Merlin L Robb, Deborah L Birx

Abstract

A number of human immunodeficiency virus type 1 (HIV-1) non-B-subtype products have been developed for present or future vaccine trials; in Thailand, several studies using subtype B and/or CRF01_AE vaccines have been conducted. To better characterize the biologic properties of these subtypes, 70 HIV-1 subtype B and E isolates were phenotyped as syncytium-inducing (SI) or non-syncytium-inducing (NSI) isolates and assessed for sensitivity to neutralizing antibody (NAb). A significantly higher number of NSI subtype E viruses were neutralization sensitive than SI subtype E viruses (P = 0.009), while no association between viral phenotype and sensitivity to NAb was observed for subtype B (P = 0.856), suggesting a difference in the neutralization patterns of subtypes B and E. Strikingly, concurrent CD4 T-cell numbers were significantly lower for subtype E-infected patients whose isolates were more resistant to NAb, both for the overall study group (P < 0.001) as well as for the 22 patients with NSI isolates (P = 0.013). Characterization of the evolution of biologic properties of both B and non-B HIV-1 subtypes will provide a clearer understanding of the repertoire of antibodies that must be elicited for a vaccine to be effective against all phenotypes and subtypes.

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