Poveda E, Hernández-Quero J, Pérez-Elías M J, Ribas M A, Martínez-Madrid O J, Flores J, Navarro J, Gutiérrez F, García-Deltoro M, Imaz A, Ocampo A, Artero A, Blanco F, Bernal E, Pasquau J, Mínguez-Gallego C, Pérez N, Aiestaran A, García F, Paredes R
Instituto de Investigación Biomédica de A Coruña (INIBIC)-Complejo Hospitalario Universitario de A Coruña (CHUAC), A Coruña, Spain.
Hospital Universitario San Cecilio, Granada, Spain.
HIV Med. 2017 Aug;18(7):482-489. doi: 10.1111/hiv.12479. Epub 2016 Dec 30.
Maraviroc (MVC) is a suitable drug for aviraemic subjects on antiretroviral treatment (ART) developing toxicity. Its prescription requires prior tropism testing. It is unknown if proviral DNA genotypic tropism testing is reliable for guiding MVC initiation in aviraemic subjects, so this study was carried out to address this issue.
PROTEST was a phase 4, prospective, single-arm clinical trial carried out in 24 HIV care centres in Spain. MVC-naïve HIV-1-infected patients with HIV-1 RNA < 50 copies/mL on stable ART during the previous 6 months who required an ART change because of toxicity and who had R5 HIV, as determined by proviral DNA genotypic tropism testing, initiated MVC with two nucleoside reverse transcriptase inhibitors (NRTIs) and were followed for 48 weeks. Virological failure was defined as two consecutive viral load measurements > 50 copies/mL.
Tropism results were available for 141 of 175 (80.6%) subjects screened: 60% had R5 and 85% of these (n = 74) were finally included in the study. Previous ART included protease inhibitors (PIs) in 62% of subjects, nonnucleoside reverse transcriptase inhibitors (NNRTIs) in 36%, and integrase inhibitors (INIs) in 2%. Main reasons for treatment change were dyslipidaemia (42%), gastrointestinal symptoms (22%) and liver toxicity (15%). MVC was given alongside tenofovir (TDF)/emtricitabine (FTC) (54%) and abacavir (ABC)/lamivudine (3TC) (40%) in most patients. Eighty-four per cent of patients maintained a viral load < 50 copies/mL to week 48, whereas 16% discontinued treatment: two withdrew informed consent, one had an R5 to X4 shift between screening and baseline, one was lost to follow-up, one developed an adverse event (rash), two died from non-study-related causes, and five developed protocol-defined virological failure.
Initiation of MVC plus two NRTIs in aviraemic subjects based on genotypic tropism testing of proviral HIV-1 DNA is associated with low rates of virological failure for up to 1 year.
马拉维若（MVC）是一种适用于接受抗逆转录病毒治疗（ART）且出现毒性反应的病毒血症阴性患者的药物。其处方需要进行预先的嗜性检测。目前尚不清楚前病毒DNA基因型嗜性检测对于指导病毒血症阴性患者开始使用MVC是否可靠，因此开展本研究以解决这一问题。
PROTEST是一项在西班牙24个HIV护理中心进行的4期前瞻性单臂临床试验。在前6个月接受稳定ART治疗且HIV-1 RNA<50拷贝/mL、因毒性反应需要改变ART方案、经前病毒DNA基因型嗜性检测确定为R5型HIV的未使用过MVC的HIV-1感染患者，开始使用MVC联合两种核苷类逆转录酶抑制剂（NRTIs）进行治疗，并随访48周。病毒学失败定义为连续两次病毒载量测量>50拷贝/mL。
在175名筛查受试者中，141名（80.6%）获得了嗜性检测结果：60%为R5型，其中85%（n = 74）最终纳入研究。既往ART方案中，62%的受试者使用过蛋白酶抑制剂（PIs），36%使用过非核苷类逆转录酶抑制剂（NNRTIs），2%使用过整合酶抑制剂（INIs）。治疗改变的主要原因是血脂异常（42%）、胃肠道症状（22%）和肝毒性（15%）。大多数患者使用MVC时联合替诺福韦（TDF）/恩曲他滨（FTC）（54%）和阿巴卡韦（ABC）/拉米夫定（3TC）（40%）。84%的患者在第48周时病毒载量维持<50拷贝/mL，而16%的患者停止治疗：2例撤回知情同意书，1例在筛查和基线之间出现R5向X4的转变，1例失访，1例发生不良事件（皮疹），2例死于与研究无关的原因，5例发生方案定义的病毒学失败。
基于HIV-1前病毒DNA基因型嗜性检测，在病毒血症阴性患者中开始使用MVC联合两种NRTIs治疗，长达1年的病毒学失败率较低。
