Ismael Nalia, Hussein Cidia, Magul Cacildo, Inguane Humberto, Couto Aleny, Nhangave Amancio, Muteerwa Ana, Bonou Mahoudo, Ramos Artur, Young Peter Wesley, Chilundo Sonia, Machekano Rhoderick, Greenberg Lauren, da Silva Juliana, Bhatt Nilesh
Instituto Nacional de Saúde, Estrada Nacional N1, Marracuene 3943, Mozambique.
Division of Medical Virology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town 8000, South Africa.
Pathogens. 2025 Jan 9;14(1):48. doi: 10.3390/pathogens14010048.
Real-world data on HIV drug resistance (HIVDR) after transitioning to tenofovir disoproxil fumarate/lamivudine/dolutegravir (TLD) are limited. We assessed HIVDR rates and patterns in clients with virological failure (VF) after switching from an NNRTI-based regimen to TLD. A cross-sectional study was conducted in Gaza, Mozambique (August 2021-February 2022), including adults on first-line ART for ≥12 months who transitioned to TLD and had unsuppressed viral load (VL) ≥ 1000 copies/mL six months post-transition. After three adherence counseling sessions, participants with VF underwent genotyping for drug resistance mutations (DRMs) using the Stanford HIVdb Program. Of 717 participants (median age 39.2 years, 70.7% female), 217 (30.2%) had VF, 193 (88.9%) underwent genotyping, with 183 (94.8%) successfully genotyped. Intermediate-high dolutegravir (DTG) resistance was found in 19.6% (36/183). Unsuppressed VL before DTG transition was independently associated with VF (aOR: 2.14). Resistance patterns included 33.3% (12/36; 95% CI: 14.6-46.3) to all three TLD drugs, 55.6% (20/36; 95% CI: 39.3-71.9) to DTG and 3TC, and 11% (4/36; 95% CI: 0.8-21.3) to DTG only. Major drug resistance mutations to DTG included G118R (9.3%), R263K (6.6%), and Q148H/R/K (4.4%). This study highlights the need to consider virologic status before transitioning PLHIV to TLD and suggests that adherence counseling may not prevent resistance in those with unknown or prior VF.
转换为富马酸替诺福韦二吡呋酯/拉米夫定/多替拉韦(TLD)治疗后,关于HIV耐药性(HIVDR)的真实世界数据有限。我们评估了从基于非核苷类逆转录酶抑制剂(NNRTI)的治疗方案转换为TLD后出现病毒学失败(VF)的患者的HIVDR发生率和模式。在莫桑比克加沙进行了一项横断面研究(2021年8月至2022年2月),纳入接受一线抗逆转录病毒治疗(ART)≥12个月、转换为TLD且转换后6个月病毒载量(VL)未得到抑制(≥1000拷贝/mL)的成年人。在进行三次依从性咨询后,VF患者使用斯坦福HIV数据库程序进行耐药突变(DRM)基因分型。717名参与者(中位年龄39.2岁,70.7%为女性)中,217名(30.2%)出现VF,193名(88.9%)接受基因分型,其中183名(94.8%)成功进行基因分型。19.6%(36/183)发现对多替拉韦(DTG)存在中高度耐药。DTG转换前VL未得到抑制与VF独立相关(调整后比值比:2.14)。耐药模式包括对所有三种TLD药物耐药的占33.3%(12/36;95%置信区间:14.6 - 46.3),对DTG和拉米夫定(3TC)耐药的占55.6%(20/36;95%置信区间:39.3 - 71.9),仅对DTG耐药的占11%(4/36;95%置信区间:0.8 - 21.3)。对DTG的主要耐药突变包括G118R(9.3%)、R263K(6.6%)和Q148H/R/K(4.4%)。本研究强调在将HIV感染者转换为TLD治疗前需考虑病毒学状态,并表明依从性咨询可能无法预防已知或既往有VF者出现耐药。