MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda.
J Virol. 2013 Aug;87(16):9053-63. doi: 10.1128/JVI.00721-13. Epub 2013 Jun 12.
HIV-exposed and yet persistently uninfected individuals have been an intriguing, repeated observation in multiple studies, but uncertainty persists on the significance and implications of this in devising protective strategies against HIV. We carried out a cross-sectional analysis of exposed uninfected partners in a Ugandan cohort of heterosexual serodiscordant couples (37.5% antiretroviral therapy naive) comparing their T cell responses to HIV peptides with those of unexposed uninfected individuals. We used an objective definition of exposure and inclusion criteria, blinded ex vivo and cultured gamma interferon (IFN-γ) enzyme-linked immunospot assays, and multiparameter flow cytometry and intracellular cytokine staining to investigate the features of the HIV-specific response in exposed versus unexposed uninfected individuals. A response rate to HIV was detectable in unexposed uninfected (5.7%, 95% confidence interval [CI] = 3.3 to 8.1%) and, at a significantly higher level (12.5%, 95% CI = 9.7 to 15.4%, P = 0.0004), in exposed uninfected individuals. The response rate to Gag was significantly higher in exposed uninfected (10/50 [20.%]) compared to unexposed uninfected (1/35 [2.9%]) individuals (P = 0.0004). The magnitude of responses was also greater in exposed uninfected individuals but not statistically significant. The average number of peptide pools recognized was significantly higher in exposed uninfected subjects than in unexposed uninfected subjects (1.21 versus 0.47; P = 0.0106). The proportion of multifunctional responses was different in the two groups, with a higher proportion of single cytokine responses, mostly IFN-γ, in unexposed uninfected individuals compared to exposed uninfected individuals. Our findings demonstrate both quantitative and qualitative differences in T cell reactivity to HIV between HESN (HIV exposed seronegative) and HUSN (HIV unexposed seronegative) subject groups but do not discriminate as to whether they represent markers of exposure or of protection against HIV infection.
HIV 暴露但持续未感染的个体在多项研究中一直是一个有趣的、反复出现的观察结果，但在制定针对 HIV 的保护策略时，这种情况的意义和影响仍存在不确定性。我们对乌干达异性恋血清不一致夫妇队列中的未感染的暴露伙伴进行了横断面分析（37.5%未经抗逆转录病毒治疗），比较了他们对 HIV 肽的 T 细胞反应与未暴露的未感染个体的反应。我们使用客观的暴露定义和纳入标准、体外和培养的γ干扰素（IFN-γ）酶联免疫斑点分析、多参数流式细胞术和细胞内细胞因子染色来研究暴露与未暴露的未感染个体中 HIV 特异性反应的特征。未暴露的未感染个体中可检测到对 HIV 的反应率（5.7%，95%置信区间[CI] = 3.3 至 8.1%），而在暴露的未感染个体中，反应率显著更高（12.5%，95%CI = 9.7 至 15.4%，P = 0.0004）。暴露的未感染个体中 Gag 的反应率明显高于未暴露的未感染个体（10/50 [20.0%] 比 1/35 [2.9%]，P = 0.0004）。暴露的未感染个体的反应幅度也更大，但无统计学意义。暴露的未感染个体中识别的肽池数量明显高于未暴露的未感染个体（1.21 比 0.47；P = 0.0106）。两组之间的多功能反应比例不同，未暴露的未感染个体中 IFN-γ 等单一细胞因子反应的比例较高，而暴露的未感染个体中则较低。我们的研究结果表明，在 HESN（HIV 暴露血清阴性）和 HUSN（HIV 未暴露血清阴性）亚组之间，T 细胞对 HIV 的反应存在数量和质量上的差异，但无法区分这些差异是暴露的标志物还是对 HIV 感染的保护标志物。
