Serwanga Jennifer, Mugaba Susan, Betty Auma, Pimego Edward, Walker Sarah, Munderi Paula, Gilks Charles, Gotch Frances, Grosskurth Heiner, Kaleebu Pontiano
MRC/UVRI Uganda Research Unit on AIDS, 51-59 Nakiwogo Road, Entebbe, Uganda.
AIDS Res Treat. 2011;2011:875028. doi: 10.1155/2011/875028. Epub 2011 Jan 18.
Objective. To better understand attributes of ART-associated HIV-induced T-cell responses that might be therapeutically harnessed. Methods. CD8(+) T-cell responses were evaluated in some HIV-1 chronically infected participants of the fixed duration STI substudy of the DART trial. Magnitudes, breadths, and functionality of IFN-γ and Perforin responses were compared in STI (n = 42) and continuous treatment (CT) (n = 46) before and after a single STI cycle when the DART STI trial was stopped early due to inferior clinical outcome in STI participants. Results. STI and CT had comparable magnitudes and breadths of monofunctional CD8(+)IFNγ(+) and CD8(+)Perforin(+) responses. However, STI was associated with significant decline in breadth of bi-functional (CD8(+)IFNγ(+)Perforin(+)) responses; P = .02, Mann-Whitney test. Conclusions. STI in individuals initiated onto ART at <200 CD4(+) T-cell counts/μl significantly reduced occurrence of bifunctional CD8(+)IFNγ(+)/Perforin(+) responses. These data add to others that found no evidence to support STI as a strategy to improve HIV-specific immunity during ART.
目的。为了更好地理解抗逆转录病毒治疗（ART）相关的HIV诱导的T细胞反应的属性，这些属性可能具有治疗用途。方法。在DART试验的性传播感染（STI）固定疗程子研究的一些HIV-1慢性感染参与者中评估CD8(+) T细胞反应。当DART STI试验因STI参与者临床结果较差而提前停止时，比较了STI组（n = 42）和持续治疗（CT）组（n = 46）在单个STI周期前后IFN-γ和穿孔素反应的强度、广度和功能。结果。STI组和CT组单功能CD8(+)IFNγ(+)和CD8(+)穿孔素(+)反应的强度和广度相当。然而，STI与双功能（CD8(+)IFNγ(+)穿孔素(+)）反应的广度显著下降有关；P = 0.02，曼-惠特尼检验。结论。在CD4(+) T细胞计数<200/μl时开始接受ART治疗的个体中，STI显著降低了双功能CD8(+)IFNγ(+)/穿孔素(+)反应的发生率。这些数据补充了其他研究，这些研究没有发现证据支持STI作为一种在ART期间改善HIV特异性免疫的策略。
