在马拉维和赞比亚以多替拉韦为基础的一线抗逆转录病毒治疗方案转换后的病毒学失败和耐药性
Virologic Failure and Drug Resistance After Programmatic Switching to Dolutegravir-based First-line Antiretroviral Therapy in Malawi and Zambia.
作者信息
Skrivankova Veronika Whitesell, Huwa Jacqueline, Muula Guy, Chiwaya Geldert D, Banda Esau, Buleya Shameem, Chihota Belinda, Chintedza Joseph, Bolton Carolyn, Tweya Hannock, Kalua Thokozani, Hossmann Stefanie, Kouyos Roger, Wandeler Gilles, Egger Matthias, Lessells Richard J
机构信息
Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
Lighthouse Trust, Lilongwe, Malawi.
出版信息
Clin Infect Dis. 2025 Feb 5;80(1):120-128. doi: 10.1093/cid/ciae261.
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).
背景
接受基于非核苷类逆转录酶抑制剂的一线抗逆转录病毒疗法（ART）的人类免疫缺陷病毒感染者（PWH）通常会换用替诺福韦-拉米夫定-度鲁特韦。我们在马拉维和赞比亚的ART项目中研究了病毒学结果和耐药情况，在马拉维，换药不考虑病毒载量，而在赞比亚，换药取决于过去一年病毒载量<1000拷贝/mL。
方法
我们使用精确方法和校正年龄及性别的逻辑回归，比较了换药时病毒载量以及不同国家之间在1年和2年时病毒血症（≥400拷贝/mL）的风险。我们对病毒载量≥1000拷贝/mL的血浆样本进行了HIV-1 pol Sanger测序。
结果
共有2832名PWH符合条件（马拉维1422名，赞比亚1410名）；中位年龄为37岁，2578名（91.0%）为女性。换药时，马拉维有77名（5.4%）病毒血症患者，赞比亚有42名（3.0%）（P = 0.001）。换药时的病毒血症与1年时（校正比值比[OR]，6.15；95%置信区间[CI]，3.13 - 11.4）和2年时（7.0；95% CI，3.73 - 12.6）的病毒血症相关。在1年时（OR，0.55；0.32 - 0.94）和2年时（OR，0.33；0.18 - 0.57），赞比亚的病毒血症发生率低于马拉维。113份符合条件的样本中有79份成功进行了整合酶测序。在5名PWH中发现了耐药突变（马拉维4名，赞比亚1名）；2名有主要突变（G118R、E138K、T66A和G118R、E138K），导致对度鲁特韦产生高水平耐药。
结论
将基于度鲁特韦的ART换药限制在病毒载量<1000拷贝/mL的PWH中，可能会降低后续病毒血症，从而减少度鲁特韦耐药突变的出现。
临床试验注册
Clinicaltrials.gov（NCT04612452）。
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