Whole Family Health Center, Vero Beach, FL, USA.
Epividian, Inc, 150 Fayetteville Street Suite 2300, Raleigh, NC, 27601, USA.
AIDS Res Ther. 2024 Oct 26;21(1):76. doi: 10.1186/s12981-024-00668-7.
Two-drug regimens (2DRs) have been introduced in recent years to potentially reduce antiretroviral therapy (ART) toxicities and drug-drug interactions while demonstrating comparable efficacy to three-drug regimens (3DRs) for people with HIV (PWH). The objective of this study was to compare the real-world effectiveness and durability of a single-tablet 2DR of dolutegravir/lamivudine (DTG/3TC) with that of commonly prescribed 3DRs in ART-experienced, virologically suppressed PWH during the first 24 months of DTG/3TC availability in the United States.
Virologically suppressed (viral load [VL] < 200 copies/mL) adult PWH initiating DTG/3TC 2DR, bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF), or a DTG-based 3DR between 01MAY2019 and 31OCT2020 were identified in the OPERA cohort and followed through 30APR2021. Univariate Poisson regression (incidence rates) and marginal structural Cox proportional hazards models with inverse probability of treatment weights (hazard ratios) were used to quantify relationships between regimen type and confirmed virologic failure (2 consecutive VLs ≥ 200 copies/mL) or regimen discontinuation. Reasons for discontinuation were examined.
A total of 8,037 ART-experienced, virologically suppressed PWH met the inclusion criteria and switched to DTG/3TC (n = 1,450), BIC/FTC/TAF (n = 5,691), or a DTG-based 3DR (n = 896). Incidence rates of confirmed virologic failure were low for all groups, at 0.66 (DTG/3TC), 0.84 (BIC/FTC/TAF), and 1.78 (DTG 3DR) per 100 person-years (py). Compared to DTG/3TC, only the DTG 3DRs were associated with a statistically significant increased hazard of confirmed virologic failure (hazard ratio: 5.21, 95% confidence interval: 1.85, 14.67). Discontinuation rates per 100 py were highest in the DTG 3DR group (24.90), followed by the DTG/3TC group (17.69) and the BIC/FTC/TAF group (8.30). Regardless of regimen, discontinuations were infrequently attributed to effectiveness (VL ≥ 200 copies/mL; 4%) or tolerability (adverse diagnoses, side effects, or lab abnormalities; 6%).
Among virologically suppressed PWH initiating a new regimen, few individuals experienced virologic failure in real-world clinical care. While rates of regimen discontinuation were high, most discontinuations could not be attributed to a lack of virologic control or poor tolerability. These findings suggest that DTG/3TC is an effective option for ART-experienced, virologically suppressed PWH.
近年来，已经引入了两药方案（2DRs），以潜在减少抗逆转录病毒治疗（ART）的毒性和药物相互作用，同时与三药方案（3DRs）在 HIV（PWH）患者中展示出相当的疗效。本研究的目的是比较在 DTG/3TC 在美可用的头 24 个月期间，接受过 ART 的病毒学抑制的 PWH 中，使用多替拉韦/拉米夫定（DTG/3TC）的单一片剂 2DR 与常用的 3DR 的真实世界疗效和持久性。
在 OPERA 队列中确定了在 2019 年 5 月 1 日至 2020 年 10 月 31 日期间开始使用 DTG/3TC 2DR、比克替拉韦/恩曲他滨/替诺福韦艾拉酚胺（BIC/FTC/TAF）或基于 DTG 的 3DR 的病毒学抑制（病毒载量 [VL] < 200 拷贝/mL）的成年 PWH，并随访至 2021 年 4 月 30 日。使用单变量泊松回归（发生率）和边际结构 Cox 比例风险模型与治疗反概率权重（风险比）来量化方案类型与确认的病毒学失败（连续 2 次 VL ≥ 200 拷贝/mL）或方案停药之间的关系。检查停药的原因。
共有 8037 名接受过 ART 的、病毒学抑制的 PWH 符合纳入标准，并转为使用 DTG/3TC（n = 1450）、BIC/FTC/TAF（n = 5691）或基于 DTG 的 3DR（n = 896）。所有组的确认病毒学失败发生率均较低，分别为每 100 人年（py）0.66（DTG/3TC）、0.84（BIC/FTC/TAF）和 1.78（DTG 3DR）。与 DTG/3TC 相比，只有基于 DTG 的 3DR 与确认的病毒学失败的风险显著增加相关（风险比：5.21，95%置信区间：1.85，14.67）。每 100 py 的停药率在基于 DTG 的 3DR 组中最高（24.90），其次是 DTG/3TC 组（17.69）和 BIC/FTC/TAF 组（8.30）。无论方案如何，停药的主要原因不是疗效（VL ≥ 200 拷贝/mL；4%）或耐受性（有效诊断、副作用或实验室异常；6%）。
在开始新方案的病毒学抑制的 PWH 中，很少有个体在真实世界的临床护理中发生病毒学失败。虽然停药率较高，但大多数停药不能归因于缺乏病毒学控制或较差的耐受性。这些发现表明 DTG/3TC 是一种有效的 ART 经验丰富、病毒学抑制的 PWH 治疗选择。
