Hoppe Anne, Giuliano Marina, Lugemwa Abbas, Thompson Jennifer A, Floridia Marco, Walker Ann S, Senoga Ismail, Abwola Mary C, Pirillo Maria F, Kityo Cissy M, Arenas-Pinto Alejandro, Paton Nicholas I
Infection and Immunity, University College London, London, United Kingdom.
MRC Clinical Trials Unit at University College London, London, United Kingdom.
Antivir Ther. 2018;23(2):191-195. doi: 10.3851/IMP3200.
HIV is transmitted primarily through sexual intercourse, and the objective of this study was therefore to assess whether there is occult viral replication and resistance in genital secretions in patients on protease inhibitor (PI)-based second-line therapy.
HIV-infected adults taking ritonavir-boosted lopinavir with either two nucleoside reverse transcriptase inhibitors (NRTIs), raltegravir or as monotherapy for 96 weeks, were enrolled at seven clinical sites in Uganda. Viral load (VL) was measured in cervico-vaginal secretions or semen and in a corresponding plasma sample. Genotypic resistance was assessed in genital secretion samples and plasma samples. Results were compared between compartments and with the plasma resistance profile at first-line failure.
Of the 111 participants enrolled (91 female, 20 male), 16 (14%) and 30 (27%) had VL >1,000 and >40 copies/ml, respectively, in plasma; 3 (3%) and 23 (21%) had VL >1,000 copies/ml and >40 copies/ml, respectively, in genital secretions. There was 74% agreement between plasma and genital secretion VL classification above/below 40 copies/ml threshold (kappa-statistic =0.29; P=0.001). RT mutations (both NRTI and non-nucleoside reverse transcriptase inhibitor) were detected in genital secretions in four patients (similar profile to corresponding plasma sample at first-line failure) and PI mutations were detected in two (one polymorphism with no impact on resistance; one with high-level PI resistance).
High level (>1,000 copies/ml) viral replication and development of new RT or PI resistance in the genital compartment were rare. The risks of transmission arising from resistance evolution in the genital compartment are likely to be low on PI-based second-line therapy.
HIV主要通过性交传播，因此本研究的目的是评估接受基于蛋白酶抑制剂（PI）的二线治疗的患者生殖器分泌物中是否存在隐匿性病毒复制和耐药性。
在乌干达的七个临床地点招募了感染HIV的成年人，他们服用利托那韦增强型洛匹那韦联合两种核苷类逆转录酶抑制剂（NRTIs）、拉替拉韦或作为单一疗法治疗96周。在宫颈阴道分泌物或精液以及相应的血浆样本中测量病毒载量（VL）。在生殖器分泌物样本和血浆样本中评估基因型耐药性。比较各部位之间的结果以及与一线治疗失败时血浆耐药谱的结果。
在纳入的111名参与者（91名女性，20名男性）中，分别有16名（14%）和30名（27%）血浆VL>1000和>40拷贝/毫升；分别有3名（3%）和23名（21%）生殖器分泌物VL>1000拷贝/毫升和>40拷贝/毫升。血浆和生殖器分泌物VL分类在40拷贝/毫升阈值以上/以下的一致性为74%（kappa统计量=0.29；P=0.001）。在四名患者的生殖器分泌物中检测到RT突变（NRTI和非核苷类逆转录酶抑制剂）（与一线治疗失败时相应血浆样本的情况相似），在两名患者中检测到PI突变（一个多态性对耐药性无影响；一个具有高水平PI耐药性）。
生殖器部位高水平（>1000拷贝/毫升）的病毒复制以及新的RT或PI耐药性的出现很少见。基于PI的二线治疗中，生殖器部位耐药性演变导致传播的风险可能较低。
