Safety and Efficacy of Triple Therapy with Dolutegravir plus Two NRTIs, in Treatment-Naïve HIV-2 Patients - Results from a 48-week Phase II Study.

BACKGROUND Integrase strand transfer inhibitor (INSTI)-based regimens are recommended for first-line therapy in HIV-2. Nonetheless, dolutegravir (DTG) clinical trial data is lacking. METHODS We conducted a phase II, single arm, open-label trial to evaluate the safety and efficacy of a triple therapy regimen including DTG, in persons with HIV-2 (PWHIV-2) in Portugal. Treatment-naïve adults were recruited to receive DTG in combination with two nucleoside reverse transcriptase inhibitors (NRTIs). Treatment efficacy was evaluated by the proportion of subjects achieving a plasma viral load (pVL) <40 copies/mL and/or by the change from baseline in CD4+T cell count and in CD4/CD8 ratio at week 48. RESULTS A total of 30 subjects were enrolled [22 women, median age 55 years-old]. At baseline, 17 (56.7%) individuals were viremic [median pVL 190 copies/mL; interquartile range (IQR): 99-445 copies/mL]. The median CD4 count was 438 cells/μL (IQR: 335-605) and CD4/CD8 ratio was 0.8. During follow-up, 3 subjects discontinued the study. At week 48, all participants (27) had pVL<40 copies/mL. No virological failures were observed. Mean changes of CD4 count and CD4/CD8 ratio at week 48 were of + 95.59 (95%CI: 28.05-163.14) cells/µL and +0.32 (95%CI: 0.19-0.46). The most common drug-related adverse events were headache and nausea. One participant discontinued due to central nervous system symptoms. No serious adverse events were reported. CONCLUSIONS DTG plus two NRTIs is safe and effective as first-line treatment for PWHIV-2 with a tolerability profile previously known. No virological failures were observed which suggest a high potency of DTG in HIV-2 as occurs in HIV-1.

背景 在HIV-2中，建议使用基于链链转移抑制剂（INSTI）方案。 方法 我们进行了II期，单臂开放标签试验，以评估包括DTG在内的三重治疗方案的安全性和效率。结合两个核侧逆转录酶抑制剂（NRTIS）。在第48周的CD4/CD8比率中。 结果 总共有30名受试者[22名妇女，中位年龄55岁]，17个（56.7％）的人是病毒的[中位数]。副本/mL。 ）最常见的不良事件是由于中枢神经系统症状而导致的一项疾病。 结论 DTG加两个NRTI是对PWHIV-2的一线治疗，且耐受性概况尚未知道，这表明HIV-2中的DTG效力很高。