Archary D, Seaton K E, Passmore J S, Werner L, Deal A, Dunphy L J, Arnold K B, Yates N L, Lauffenburger D A, Bergin P, Liebenberg L J, Samsunder N, Mureithi M W, Altfeld M, Garrett N, Karim Q Abdool, Karim Ss Abdool, Morris L, Tomaras G D
Centre for the AIDS Program of Research in South Africa, University of KwaZulu-Natal, Durban, South Africa.
Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
Mucosal Immunol. 2016 May;9(3):821-833. doi: 10.1038/mi.2015.145. Epub 2016 Jan 27.
The impact of topical antiretrovirals for pre-exposure prophylaxis on humoral responses following HIV infection is unknown. Using a binding antibody multiplex assay, we investigated HIV-specific IgG and IgA responses to envelope glycoproteins, p24 Gag and p66, in the genital tract (GT) and plasma following HIV acquisition in women assigned to tenofovir gel (n=24) and placebo gel (n=24) in the CAPRISA 004 microbicide trial to assess if this topical antiretroviral had an impact on mucosal and systemic antibody responses. Linear mixed effect modeling and partial least squares discriminant analysis was used to identify multivariate antibody signatures associated with tenofovir use. There were significantly higher response rates to gp120 Env (P=0.03), p24 (P=0.002), and p66 (P=0.009) in plasma and GT in women assigned to tenofovir than placebo gel at multiple time points post infection. Notably, p66 IgA titers in the GT and plasma were significantly higher in the tenofovir compared with the placebo arm (P<0.05). Plasma titers for 9 of the 10 HIV-IgG specificities predicted GT levels. Taken together, these data suggest that humoral immune responses are increased in blood and GT of individuals who acquire HIV infection in the presence of tenofovir gel.
暴露前预防用局部抗逆转录病毒药物对HIV感染后体液免疫反应的影响尚不清楚。在CAPRISA 004杀微生物剂试验中，我们使用结合抗体多重检测法，研究了分配使用替诺福韦凝胶（n = 24）和安慰剂凝胶（n = 24）的女性在感染HIV后，生殖道（GT）和血浆中针对包膜糖蛋白、p24 Gag和p66的HIV特异性IgG和IgA反应，以评估这种局部抗逆转录病毒药物是否对黏膜和全身抗体反应有影响。采用线性混合效应模型和偏最小二乘判别分析来确定与替诺福韦使用相关的多变量抗体特征。在感染后的多个时间点，分配使用替诺福韦的女性血浆和GT中对gp120 Env（P = 0.03）、p24（P = 0.002）和p66（P = 0.009）的反应率显著高于使用安慰剂凝胶的女性。值得注意的是，与安慰剂组相比，替诺福韦组GT和血浆中的p66 IgA滴度显著更高（P < 0.05）。10种HIV-IgG特异性中的9种血浆滴度可预测GT水平。综上所述，这些数据表明，在有替诺福韦凝胶存在的情况下感染HIV的个体，其血液和GT中的体液免疫反应会增强。
