Mondi Annalisa, Pinnetti Carmela, Lorenzini Patrizia, Plazzi Maria Maddalena, Abbate Isabella, Camici Marta, Agrati Chiara, Grilli Elisabetta, Gili Francesca, Esvan Rozenn, Orchi Nicoletta, Rozera Gabriella, Amendola Alessandra, Forbici Federica, Gori Caterina, Gagliardini Roberta, Bellagamba Rita, Ammassari Adriana, Cicalini Stefania, Capobianchi Maria Rosaria, Antinori Andrea
HIV/AIDS Department, National Institute for Infectious Diseases, Lazzaro Spallanzani IRCCS, 00149 Rome, Italy.
Laboratory of Virology, National Institute for Infectious Diseases, Lazzaro Spallanzani IRCCS, 00149 Rome, Italy.
Pharmaceuticals (Basel). 2022 Mar 26;15(4):403. doi: 10.3390/ph15040403.
The optimal therapeutic approach for primary HIV infection (PHI) is still debated. We aimed to compare the viroimmunological response to a four- versus a three-drug regimen, both INSTI-based, in patients with PHI. This was a monocentric, prospective, observational study including all patients diagnosed with PHI from December 2014 to April 2018. Antiretroviral therapy (ART) was started, before genotype resistance test results, with tenofovir/emtricitabine and either raltegravir plus boosted darunavir or dolutegravir. Cumulative probability of virological suppression [VS] (HIV-1 RNA< 40 cp/mL), low-level HIV-1 DNA [LL-HIVDNA] (HIV-1 DNA < 200 copies/106PBMC), and CD4/CD8 ratio ≥1 were estimated using Kaplan−Meier curves. Factors associated with the achievement of VS, LL-HIVDNA, and CD4/CD8 ≥ 1 were assessed by a Cox regression model. We enrolled 144 patients (95.8% male, median age 34 years): 110 (76%) started a four-drug-based therapy, and 34 (24%) a three-drug regimen. Both treatment groups showed a comparable high probability of achieving VS and a similar probability of reaching LL-HIVDNA and a CD4/CD8 ratio ≥1 after 48 weeks from ART initiation. Higher baseline HIV-1 RNA and HIV-1 DNA levels lowered the chance of VS, whereas a better preserved immunocompetence increased that chance. Not statistically significant factors associated with LL-HIVDNA achievement were found, whereas a higher baseline CD4/CD8 ratio predicted the achievement of immune recovery. In PHI patients, the rapid initiation of either an intensified four-drug or a standard three-drug INSTI-based regimen showed comparable responses in terms of VS, viral reservoir size, and immunological recovery.
原发性HIV感染(PHI)的最佳治疗方法仍存在争议。我们旨在比较基于整合酶链转移抑制剂(INSTI)的四联方案与三联方案对PHI患者的病毒免疫反应。这是一项单中心、前瞻性、观察性研究,纳入了2014年12月至2018年4月期间所有诊断为PHI的患者。在获得基因型耐药检测结果之前,开始抗逆转录病毒治疗(ART),使用替诺福韦/恩曲他滨,联合raltegravir加增效达芦那韦或度鲁特韦。使用Kaplan-Meier曲线估计病毒学抑制(VS)(HIV-1 RNA<40拷贝/mL)、低水平HIV-1 DNA[LL-HIVDNA](HIV-1 DNA<200拷贝/106外周血单核细胞)和CD4/CD8比值≥1的累积概率。通过Cox回归模型评估与实现VS、LL-HIVDNA和CD4/CD8≥1相关的因素。我们纳入了144例患者(95.8%为男性,中位年龄34岁):110例(76%)开始基于四联药物的治疗,34例(24%)开始三联方案治疗。两个治疗组在ART开始48周后实现VS的概率相当高,达到LL-HIVDNA和CD4/CD8比值≥1的概率相似。较高的基线HIV-1 RNA和HIV-1 DNA水平降低了实现VS的机会,而较好的免疫功能储备增加了这种机会。未发现与实现LL-HIVDNA相关的具有统计学意义的因素,而较高的基线CD4/CD8比值预测了免疫恢复的实现。在PHI患者中,快速启动强化四联或标准三联基于INSTI的方案在VS、病毒储存库大小和免疫恢复方面显示出相当的反应。