Prada Nicole, Davis Brandi, Jean-Pierre Patrick, La Roche Matthew, Duh Fuh-Mei, Carrington Mary, Poles Michael, Mehandru Saurabh, Mohri Hiroshi, Markowitz Martin
Aaron Diamond AIDS Research Center, Rockefeller University, 455 First Avenue, New York, NY 10016, USA.
J Acquir Immune Defic Syndr. 2008 Oct 1;49(2):117-22. doi: 10.1097/QAI.0b013e3181869a9b.
Continued high rates of HIV-1 transmission have fueled interest in the use of antiretrovirals to prevent infection. Attenuated infection with failure of tenofovir as prophylaxis has been reported in animal models. Here, we report a case of HIV-1 infection despite intermittent use of fixed-dose combination tenofovir and emtricitabine (FTC).
The patient was treated with tenofovir DF/FTC for reported repeated high-risk sexual exposures. After seroconversion, he was subjected to routine laboratory testing, CCR5 and HLA genotyping, and biopsy of gastrointestinal (GI) tissue. Resistance testing was performed both as bulk sequencing of plasma and cloning and sequencing of virus derived from plasma, peripheral blood mononuclear cells, and GI tissue.
In this patient with no readily identifiable modifying host factors, acute HIV-1 infection with tenofovir DF/FTC-susceptible HIV-1 was associated with an attenuated clinical course, very low postseroconversion HIV-1 RNA levels, slow kinetics of seroconversion, and relative sparing of mucosal CD4+ T cells in the GI tract.
Despite the failure of tenofovir DF/FTC as prophylaxis, selection for drug-resistant transmission did not occur and the blunting of postinfection levels of viremia likely reduced the probability of subsequent forward transmissions during the acute phase. These results support continued investigations of the use of antiretrovirals as a means to reduce HIV-1 transmission.
HIV-1持续的高传播率激发了人们对抗逆转录病毒药物用于预防感染的兴趣。在动物模型中已报道替诺福韦作为预防用药时出现感染减弱但失败的情况。在此,我们报告一例尽管间歇性使用固定剂量复方替诺福韦和恩曲他滨(FTC)仍发生HIV-1感染的病例。
该患者因报告有多次高危性接触而接受替诺福韦酯/FTC治疗。血清转化后,他接受了常规实验室检测、CCR5和HLA基因分型以及胃肠道(GI)组织活检。耐药性检测通过血浆的批量测序以及从血浆、外周血单个核细胞和GI组织中分离出的病毒的克隆和测序来进行。
在这位没有易于识别的宿主修饰因素的患者中,感染对替诺福韦酯/FTC敏感的HIV-1的急性感染与临床病程减弱、血清转化后HIV-1 RNA水平极低、血清转化动力学缓慢以及胃肠道黏膜CD4+ T细胞相对未受影响有关。
尽管替诺福韦酯/FTC预防用药失败,但未发生耐药性传播毒株的选择,感染后病毒血症水平的降低可能降低了急性期后续传播的可能性。这些结果支持继续研究将抗逆转录病毒药物作为减少HIV-1传播的一种手段。