多替拉韦/拉米夫定联合治疗初治CD4细胞计数<200/mm³患者的疗效和安全性：DOLCE研究的48周结果

Efficacy and Safety of Dual Therapy With Dolutegravir/Lamivudine in Treatment-naive Persons With CD4 Counts <200/mm3: 48-Week Results of the DOLCE Study.

作者信息

Figueroa Maria Ines, Brites Carlos, Cecchini Diego, Ramalho Aline, Francos Jose Luis, Lacerda Marcus, Rolon Maria Jose, Madruga Jose Valdez, Sprinz Eduardo, Souza Tamara Newman Lobato, Parenti Pablo, Converso Daniela, Mernies Gissella, Sued Omar, Cahn Pedro

机构信息

Research Department, Fundación Huésped, Ciudad de Buenos Aires, Argentina.

Infectious Diseases Department, Fundação Bahiana de Infectologia, Salvador, Bahia, Brazil.

出版信息

Clin Infect Dis. 2025 Aug 28. doi: 10.1093/cid/ciaf415.

DOI:10.1093/cid/ciaf415

PMID:40874763

Abstract

BACKGROUND

Dolutegravir (DTG)/lamivudine dual therapy (DT) has demonstrated noninferiority to triple therapy (TT) in the GEMINI trials. Although the population with ≤200 CD4 cells/mm3 had a lower response rate, this was unrelated to virological failure. This trial evaluated the antiviral activity of dolutegravir/lamivudine among antiretroviral therapy (ART)-naive patients with human immunodeficiency virus (HIV) with a CD4 count ≤200 cells/mm3.

METHODS

DOLCE is a randomized, hypothesis-based, open-label, multicenter study l, assessing the antiviral efficacy of DTG/3TC at week 48 in treatment-naive people with HIV (PWH) with CD4 counts ≤200 cells/mm3. Participants were randomly assigned in a 2:1 ratio to receive DTG/3TC as a single tablet regimen or DTG plus Tenofovir disoproxil fumarate (TDF)/XTC: Emtricitabine or lamivudine (FTC or 3TC). The primary endpoint was the proportion of participants with pVL <50 copies/mL at week 48 (Food and Drug Administration snapshot analysis intent-to-treat exposed population). This report presents results at week 48.

RESULTS

Baseline characteristics were similar in both arms. In the DT arm, median CD4 cell count was 109 cells/mm (interquartile range [IQR]: 49-177) and median pVL was 180,000 copies/mL (IQR: 53 309-468 691); 45.4% had CD4 <100 cells/mm3, and 61.4% had pVL >100 000 copies/mL. CDC (Centers for Disease Control and Prevention) stage C: 31.4%. At week 48, virological suppression (pVL <50 copies/mL) was achieved 82.2% in the DT (125/152), and the CD4 count increased by +200 cells/mm3. Per-protocol analysis showed a response rate of 91.9%. Severe adverse events (n = 17) were reported in 15 of 152 participants (11.1%).

CONCLUSIONS

Dolutegravir/3TC demonstrated high efficacy in a population with low CD4 counts and high viral load. This study adds information regarding the efficacy and safety of DTG/3TC, regardless of baseline CD4 counts and viral load.

CLINICAL TRIALS REGISTRATION

NCT04880395.

摘要

背景

在GEMINI试验中，多替拉韦（DTG）/拉米夫定双联疗法（DT）已证明不劣于三联疗法（TT）。尽管CD4细胞≤200个/mm³的人群缓解率较低，但这与病毒学失败无关。本试验评估了多替拉韦/拉米夫定在初治的人类免疫缺陷病毒（HIV）且CD4计数≤200个/mm³患者中的抗病毒活性。

方法

DOLCE是一项基于假设的随机、开放标签、多中心研究，评估DTG/3TC在第48周时对初治的HIV感染者（PWH）且CD4计数≤200个/mm³的抗病毒疗效。参与者按2:1的比例随机分配，接受DTG/3TC单片制剂或DTG加替诺福韦酯（TDF）/恩曲他滨（FTC）或拉米夫定（3TC）。主要终点是第48周时血浆病毒载量（pVL）<50拷贝/mL的参与者比例（美国食品药品监督管理局快照分析意向性治疗暴露人群）。本报告展示了第48周时的结果。

结果

两组的基线特征相似。在DT组中，CD4细胞计数中位数为109个/mm³（四分位间距[IQR]：49 - 177），pVL中位数为180,000拷贝/mL（IQR：53309 - 468691）；45.4%的患者CD4<100个/mm³，61.4%的患者pVL>100,000拷贝/mL。美国疾病控制与预防中心（CDC）C期：31.4%。在第48周时，DT组中82.2%（125/152）实现了病毒学抑制（pVL<50拷贝/mL），且CD4计数增加了200个/mm³。符合方案分析显示缓解率为91.9%。152名参与者中有15名（11.1%）报告了严重不良事件（n = 17）。