van Heerden Jennifer K, Zhao Ying, Keene Claire M, Griesel Rulan, Omar Zaayid, Goliath René, Delaney Kayla, van Zyl Gert, Maartens Gary, Meintjes Graeme
Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
Department of Biochemistry, Medical Sciences Division, University of Oxford, Oxford, United Kingdom.
South Afr J HIV Med. 2025 Apr 30;26(1):1677. doi: 10.4102/sajhivmed.v26i1.1677. eCollection 2025.
Dolutegravir in second-line antiretroviral therapy (ART) is more effective with recycled tenofovir than switching to zidovudine. However, dolutegravir resistance is more frequent in second-line compared to first-line ART.
We report long-term virologic outcomes from a clinical trial.
AntiRetroviral Therapy In Second-line: investigating Tenofovir-lamivudine-dolutegravir (ARTIST) was a randomised, double-blind, phase II clinical trial. Eligible participants had two consecutive HIV-1 RNA ≥ 1000 copies/mL on first-line ART, mostly tenofovir-emtricitabine-efavirenz. Participants were switched to tenofovir-lamivudine-dolutegravir (TLD) with lead-in 50 mg dolutegravir twice daily in stage one ( = 62), and randomised to TLD with additional lead-in 50 mg dolutegravir or placebo for the first 14 days in stage two ( = 130). We present results up to 158 weeks, combining stages one and two.
We enrolled 192 participants: 127/176 (72%) had resistance (Stanford score ≥ 15) to both tenofovir and lamivudine. At week 48, 151/186 (81%; 95% confidence interval [CI] 75%, 87%) had HIV-1 RNA < 50 copies/mL. Of 127 participants with follow-up through week 158, 78% (95% CI 70%, 85%) maintained HIV-1 RNA < 50 copies/mL, 11% had HIV-1 RNA 50-999 copies/mL, and 11% had HIV-1 RNA ≥ 1000 copies/mL. Twenty-nine participants met criteria for resistance testing: one developed intermediate-level dolutegravir resistance (G118R mutation) at week 96, and one had high-level dolutegravir resistance (E138K, G118R, G163R, T66A mutations) detected at week 146.
Among adults switching to TLD with detectable HIV-1 RNA and substantial tenofovir and lamivudine resistance, a high proportion maintained virologic suppression up to 158 weeks. Emergent dolutegravir resistance occurred in ~1% of participants after 2-3 years on second-line TLD.
在二线抗逆转录病毒疗法（ART）中，多替拉韦与循环使用替诺福韦联合使用比换用齐多夫定更有效。然而，与一线ART相比，二线治疗中多替拉韦耐药更为常见。
我们报告一项临床试验的长期病毒学结果。
二线抗逆转录病毒疗法：替诺福韦-拉米夫定-多替拉韦研究（ARTIST）是一项随机、双盲、II期临床试验。符合条件的参与者在一线ART（大多为替诺福韦-恩曲他滨-依非韦伦）治疗期间连续两次HIV-1 RNA≥1000拷贝/毫升。参与者在第一阶段换用替诺福韦-拉米夫定-多替拉韦（TLD），先每日两次导入50毫克多替拉韦（n = 62），在第二阶段随机分为在开始的14天额外导入50毫克多替拉韦的TLD组或安慰剂组（n = 130）。我们呈现了结合第一阶段和第二阶段长达158周的结果。
我们纳入了192名参与者：127/176（72%）对替诺福韦和拉米夫定均有耐药（斯坦福评分≥15）。在第48周时，151/186（81%；95%置信区间[CI] 75%，87%）的HIV-1 RNA < 50拷贝/毫升。在127名随访至第158周的参与者中，78%（95% CI 70%，85%）的HIV-1 RNA维持在< 50拷贝/毫升，11%的HIV-1 RNA为50 - 999拷贝/毫升，11%的HIV-1 RNA≥1000拷贝/毫升。29名参与者符合耐药检测标准：1名在第96周出现中级多替拉韦耐药（G118R突变），1名在第146周检测到高级多替拉韦耐药（E138K、G118R、G163R、T66A突变）。
在HIV-1 RNA可检测且对替诺福韦和拉米夫定有显著耐药的成人中换用TLD，高达158周时很大一部分人维持了病毒学抑制。在二线TLD治疗2 - 3年后，约1%的参与者出现了多替拉韦耐药。
