Scholarlink

Introduction <p>Long-term use of tenofovir disoproxil fumarate (TDF) is associated with renal tubular dysfunction and bone mineral loss. In virologically suppressed people living with HIV (PLWH), optimizing antiretroviral therapy requires maintaining viral suppression while minimizing cumulative drug-related toxicity. We therefore evaluated the efficacy and safety of switching to dolutegravir/lamivudine (DTG/3TC) in Chinese PLWH with TDF-related renal or bone toxicity.</p> Methods <p>This prospective, single-center, open-label cohort study enrolled adults with HIV-1 RNA &lt; 40 copies/ml for ≥ 6&#xa0;months on TDF-based regimens and evidence of TDF-associated renal or bone toxicity. Participants were switched to DTG/3TC and followed for 48&#xa0;weeks. The primary endpoint was virological failure at week 48 (FDA Snapshot algorithm). Secondary endpoints included changes in CD4 + T-cell counts, renal tubular biomarkers, bone mineral density (BMD), metabolic parameters, and safety outcomes.</p> Results <p>One hundred participants were enrolled; 91 completed the study per protocol. Median age was 45&#xa0;years and 90% were male. At week 48, virological suppression was maintained in 90% of the intention-to-treat–exposed population and 99% of the per-protocol population. CD4 + T-cell counts increased significantly at week 48 (+ 77.4 cells/μl; <i>p</i> &lt; 0.001). Markers of proximal tubular dysfunction improved significantly, including reductions in urinary β2-microglobulin-to-creatinine ratio, urine albumin-to-creatinine ratio, and urinary retinol-binding protein-to-creatinine ratio (all <i>p</i> &lt; 0.001). BMD increased in the lumbar spine and hip (both <i>p</i> &lt; 0.001). Modest weight gain (+ 2.17&#xa0;kg) and small increases in total cholesterol and low-density lipoprotein cholesterol were observed at week 48.</p> Conclusions <p>In virologically suppressed Chinese PLWH with TDF-related renal or bone toxicity, switching to DTG/3TC maintained viral suppression and was associated with significant improvements in renal tubular and bone metabolic markers over 48&#xa0;weeks. DTG/3TC represents a well-tolerated toxicity-driven switch strategy in routine clinical practice.</p> Trial Registration <p>ClinicalTrial.gov ID: NCT05493969.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Efficacy and Safety of Switching to Dolutegravir/Lamivudine in Virologically Suppressed HIV-1 Infected Adults with TDF-Related Renal or Bone Toxicity

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月20日

查看全文
  • Zhenyan Wang,
  • Li Liu,
  • Jun Chen,
  • Jiangrong Wang,
  • Yinzhong Shen,
  • Tangkai Qi,
  • Yang Tang,
  • Wei Song,
  • Jianjun Sun,
  • Shuibao Xu,
  • Junyang Yang,
  • Youming Chen,
  • Yueming Shao,
  • Renfang Zhang

摘要

Introduction

Long-term use of tenofovir disoproxil fumarate (TDF) is associated with renal tubular dysfunction and bone mineral loss. In virologically suppressed people living with HIV (PLWH), optimizing antiretroviral therapy requires maintaining viral suppression while minimizing cumulative drug-related toxicity. We therefore evaluated the efficacy and safety of switching to dolutegravir/lamivudine (DTG/3TC) in Chinese PLWH with TDF-related renal or bone toxicity.

Methods

This prospective, single-center, open-label cohort study enrolled adults with HIV-1 RNA < 40 copies/ml for ≥ 6 months on TDF-based regimens and evidence of TDF-associated renal or bone toxicity. Participants were switched to DTG/3TC and followed for 48 weeks. The primary endpoint was virological failure at week 48 (FDA Snapshot algorithm). Secondary endpoints included changes in CD4 + T-cell counts, renal tubular biomarkers, bone mineral density (BMD), metabolic parameters, and safety outcomes.

Results

One hundred participants were enrolled; 91 completed the study per protocol. Median age was 45 years and 90% were male. At week 48, virological suppression was maintained in 90% of the intention-to-treat–exposed population and 99% of the per-protocol population. CD4 + T-cell counts increased significantly at week 48 (+ 77.4 cells/μl; p < 0.001). Markers of proximal tubular dysfunction improved significantly, including reductions in urinary β2-microglobulin-to-creatinine ratio, urine albumin-to-creatinine ratio, and urinary retinol-binding protein-to-creatinine ratio (all p < 0.001). BMD increased in the lumbar spine and hip (both p < 0.001). Modest weight gain (+ 2.17 kg) and small increases in total cholesterol and low-density lipoprotein cholesterol were observed at week 48.

Conclusions

In virologically suppressed Chinese PLWH with TDF-related renal or bone toxicity, switching to DTG/3TC maintained viral suppression and was associated with significant improvements in renal tubular and bone metabolic markers over 48 weeks. DTG/3TC represents a well-tolerated toxicity-driven switch strategy in routine clinical practice.

Trial Registration

ClinicalTrial.gov ID: NCT05493969.