Virologic Failure and Drug Resistance After Programmatic Switching to Dolutegravir-based First-line Antiretroviral Therapy in Malawi and Zambia.

IF 8.2 1区医学 Q1 IMMUNOLOGY

Clinical Infectious Diseases Pub Date : 2025-02-05 DOI:10.1093/cid/ciae261

Veronika Whitesell Skrivankova, Jacqueline Huwa, Guy Muula, Geldert D Chiwaya, Esau Banda, Shameem Buleya, Belinda Chihota, Joseph Chintedza, Carolyn Bolton, Hannock Tweya, Thokozani Kalua, Stefanie Hossmann, Roger Kouyos, Gilles Wandeler, Matthias Egger, Richard J Lessells

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引用次数: 0

Abstract

Background: People with human immunodeficiency virus (PWH) on first-line, nonnucleoside reverse-transcriptase inhibitor-based antiretroviral therapy (ART) were routinely switched to tenofovir-lamivudine-dolutegravir. We examined virologic outcomes and drug resistance in ART programs in Malawi, where switching was irrespective of viral load, and Zambia, where switching depended on a viral load <1000 copies/mL in the past year.

Methods: We compared the risk of viremia (≥400 copies/mL) at 1 and 2 years by viral load at switch and between countries using exact methods and logistic regression adjusted for age and sex. We performed HIV-1 pol Sanger sequencing on plasma samples with viral load ≥1000 copies/mL.

Results: A total of 2832 PWH were eligible (Malawi 1422, Zambia 1410); the median age was 37 years, and 2578 (91.0%) were women. At switch, 77 (5.4%) were viremic in Malawi and 42 (3.0%) in Zambia (P = .001). Viremia at switch was associated with viremia at 1 year (adjusted odds ratio (OR), 6.15; 95% confidence interval [CI], 3.13-11.4) and 2 years (7.0; 95% CI, 3.73-12.6). Viremia was less likely in Zambia than in Malawi at 1 year (OR, 0.55; 0.32-0.94) and 2 years (OR, 0.33; 0.18-0.57). Integrase sequencing was successful for 79 of 113 eligible samples. Drug resistance mutations were found in 5 PWH (Malawi 4, Zambia 1); 2 had major mutations (G118R, E138K, T66A and G118R, E138K) leading to high-level dolutegravir resistance.

Conclusions: Restricting switching to dolutegravir-based ART to PWH with a viral load <1000 copies/mL may reduce subsequent viremia and, consequently, the emergence of dolutegravir drug resistance mutations.

Clinical trials registration: Clinicaltrials.gov (NCT04612452).

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马拉维和赞比亚计划性转用基于多鲁特韦的一线抗逆转录病毒疗法后的病毒学失败和耐药性。

背景：接受一线非核苷类逆转录酶抑制剂抗逆转录病毒疗法（ART）的人类免疫缺陷病毒（PWH）感染者按惯例转用替诺福韦酯-拉米夫定-多罗替韦。我们研究了马拉维和赞比亚抗逆转录病毒疗法项目的病毒学结果和耐药性，马拉维的转换与病毒载量无关，而赞比亚的转换则取决于病毒载量方法：我们采用精确法和逻辑回归法，并根据年龄和性别进行调整，比较了不同病毒载量在转药时以及不同国家间 1 年和 2 年的病毒血症（≥400 拷贝/毫升）风险。我们对病毒载量≥1000拷贝/毫升的血浆样本进行了HIV-1 pol Sanger测序：共有 2832 名感染者符合条件（马拉维 1422 人，赞比亚 1410 人）；年龄中位数为 37 岁，2578 人（91.0%）为女性。转换时，马拉维有 77 人（5.4%）为病毒携带者，赞比亚有 42 人（3.0%）为病毒携带者（P = .001）。转换时的病毒血症与 1 年（调整后的几率比 (OR)，6.15；95% 置信区间 [CI]，3.13-11.4）和 2 年（7.0；95% 置信区间，3.73-12.6）的病毒血症相关。赞比亚在 1 年（OR，0.55；0.32-0.94）和 2 年（OR，0.33；0.18-0.57）后出现病毒血症的可能性低于马拉维。113 份合格样本中有 79 份成功进行了整合酶测序。在5名PWH（马拉维4人，赞比亚1人）中发现了耐药性突变；其中2人有重大突变（G118R, E138K, T66A和G118R, E138K），导致对多鲁特韦产生高度耐药性：结论：限制病毒载量达标的 PWH 转用基于多鲁曲韦的抗逆转录病毒疗法：临床试验注册：Clinicaltrials.gov (NCT04612452)。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical Infectious Diseases 医学-传染病学

CiteScore

25.00

自引率

2.50%

发文量

900

审稿时长

3 months

期刊介绍： Clinical Infectious Diseases (CID) is dedicated to publishing original research, reviews, guidelines, and perspectives with the potential to reshape clinical practice, providing clinicians with valuable insights for patient care. CID comprehensively addresses the clinical presentation, diagnosis, treatment, and prevention of a wide spectrum of infectious diseases. The journal places a high priority on the assessment of current and innovative treatments, microbiology, immunology, and policies, ensuring relevance to patient care in its commitment to advancing the field of infectious diseases.