Pei Pamela P, Jones Michelle, Hu Ruitian, Chen Wanyi, Sax Paul E, Pandya Ankur, Gandhi Monica, Eron Joseph J, Currier Judith S, Wilkin Timothy J, Reddy Krishna P, Qoshe Livia, Hyle Emily P, Freedberg Kenneth A
Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, Massachusetts, USA.
Harvard Medical School, Boston, Massachusetts, USA.
Clin Infect Dis. 2025 Aug 4. doi: 10.1093/cid/ciaf428.
People with HIV (PWH) with persistent viremia and adherence challenges to oral antiretroviral therapy (ART) can achieve viral suppression (VS) with long-acting cabotegravir/rilpivirine (LA-CAB/RPV). US guidelines, however, recommend CAB/RPV only in limited situations. We projected the impact of delaying LA-CAB/RPV implementation while awaiting trial data.
Using a microsimulation model, we considered 2 approaches for PWH with persistent viremia and intermittent care engagement: daily first-line oral ART or LA-CAB/RPV, both with intensive-support-services (ISS) to maximize adherence. We evaluated 4 CAB/RPV implementation scenarios: 1) Current practice (1% on CAB/RPV); 2) hypothetical Immediate/Delayed complete implementation (100% CAB/RPV after 0-4 yr); 3) two Post-trial implementation scenarios: Post-one-arm-trial implementation (1yr-trial, 5% uptake/yr thereafter), Post-randomized-trial implementation (3yr-trial, 15% uptake/yr thereafter; 4) Immediate incomplete implementation (1-20% uptake/yr). Outcomes were virologically-suppressed person-years (VSPY) and 5yr-mortality. Inputs included cohort size 33,600, initial CD4 count 150/µl, 6-month-VS from observational data: 23% (oral ART), 65% (LA-CAB/RPV).
Current practice projects 35,810 VSPY and 17,640 deaths at 5yrs. Immediate complete implementation increases VSPY by 26,830 and averts 3,980 deaths; Delayed complete implementation produces 5,370 fewer VSPY and 800 more deaths/delayed year. Post-one-arm-trial implementation yields 1,700 more VSPY and 330 fewer deaths than Current practice; Post-randomized-trial implementation yields 1,280 more VSPY and 270 fewer deaths. Immediate incomplete implementation at 3% and 2% uptake/yr is similar to Post-one-arm-trial implementation and Post-randomized-trial implementation.
LA-CAB/RPV for US PWH with persistent viremia and intermittent care engagement would increase VS and decrease mortality. Increased LA-CAB/RPV implementation with intensive-support-services should be undertaken while awaiting trial results.
持续性病毒血症且在口服抗逆转录病毒疗法（ART）中存在依从性问题的艾滋病毒感染者（PWH）可通过长效卡博特韦/利匹韦林（LA-CAB/RPV）实现病毒抑制（VS）。然而，美国指南仅在有限情况下推荐使用CAB/RPV。我们预测了在等待试验数据期间延迟实施LA-CAB/RPV的影响。
使用微观模拟模型，我们考虑了两种针对持续性病毒血症和间歇性接受治疗的PWH的方法：每日一线口服ART或LA-CAB/RPV，两者均配备强化支持服务（ISS）以最大化依从性。我们评估了4种CAB/RPV实施方案：1）当前做法（1%使用CAB/RPV）；2）假设的立即/延迟完全实施（0至4年后100%使用CAB/RPV）；3）两种试验后实施方案：单臂试验后实施（1年试验，此后每年采用率5%），随机试验后实施（3年试验，此后每年采用率15%）；4）立即不完全实施（每年采用率1%至20%）。结局指标为病毒学抑制人年数（VSPY）和5年死亡率。输入数据包括队列规模33600、初始CD4细胞计数150/µl、来自观察数据的6个月病毒抑制率：23%（口服ART），65%（LA-CAB/RPV）。
当前做法预计5年后有35810个VSPY和17640例死亡。立即完全实施可使VSPY增加26830，并避免3980例死亡；延迟完全实施导致VSPY减少5370，且每延迟一年死亡人数增加800。单臂试验后实施比当前做法产生多1700个VSPY和少330例死亡；随机试验后实施产生多1280个VSPY和少270例死亡。每年采用率为3%和2%的立即不完全实施与单臂试验后实施和随机试验后实施相似。
对于美国持续性病毒血症且间歇性接受治疗的PWH，LA-CAB/RPV可增加病毒抑制并降低死亡率。在等待试验结果期间，应在强化支持服务的情况下增加LA-CAB/RPV的实施。
