Department of Health Sciences (DISSAL), University of Genoa, Italy.
Hygiene Unit, San Martino Policlinico Hospital - IRCCS for Oncology and Neurosciences, Genoa, Italy.
New Microbiol. 2023 May;46(2):226-230.
Management of heavily treatment experienced (HTE) people with HIV remains a challenge. Tailored antiretroviral therapy (ART) is needed in this fragile population who almost invariably harbor viral quasispecies with resistance-associated mutations (RAMs). The reference method for HIV genotypic resistance testing (GRT) has long been Sanger sequencing (SS), but next-generation sequencing (NGS), following recent progress in workflow and cost-effectiveness, is replacing SS because of higher sensitivity. From the PRESTIGIO Registry, we present a case of a 59-year-old HTE woman who failed darunavir/ritonavir plus raltegravir at low-viremia levels due mainly to high pill burden and poor adherence. NGS-GRT was performed on HIV-RNA at failure and the results were compared to all past SS-GRT data available (historical genotype). In this case, NGS-GRT did not detect any minority drug-resistant variants. After discussing several therapeutic options, the treatment was changed to dolutegravir 50 mg twice daily plus doravirine 100 mg once a day, based on clinical history, adherence issues, and pill burden, as well as the historical SS-GRT and the latest NGS-GRT results. At six months follow-up visit, the patient had HIV-RNA below 30 copies/ml and CD4+ T cell count increased from 673 cells/ mm3 to 688 cells/ mm3. Close follow-up of this patient is ongoing.
对于治疗经验丰富(HTE)的 HIV 感染者的管理仍然是一个挑战。在这个脆弱的人群中,需要量身定制的抗逆转录病毒疗法(ART),因为他们几乎无一例外地携带具有耐药相关突变(RAMs)的病毒准种。HIV 基因型耐药检测(GRT)的参考方法长期以来一直是 Sanger 测序(SS),但由于灵敏度更高,下一代测序(NGS)在工作流程和成本效益方面的最新进展正在取代 SS。从 PRESTIGIO 登记处,我们报告了一例 59 岁的 HTE 女性,由于高药物负担和低依从性,她在低病毒血症水平下失败了达芦那韦/利托那韦加雷特格韦。在失败时对 HIV-RNA 进行了 NGS-GRT,并将结果与所有可用的过去 SS-GRT 数据(历史基因型)进行了比较。在这种情况下,NGS-GRT 未检测到任何少数耐药变异体。在讨论了几种治疗选择后,根据临床病史、依从性问题和药物负担,以及历史 SS-GRT 和最新的 NGS-GRT 结果,治疗方案更改为每日两次 50 毫克多替拉韦和每日一次 100 毫克多拉韦林。在六个月的随访中,患者的 HIV-RNA 低于 30 拷贝/ml,CD4+T 细胞计数从 673 个细胞/mm3增加到 688 个细胞/mm3。对该患者的密切随访仍在继续。