Institute of Infection & Global Health, University of Liverpool, Liverpool, UK.
MRC Clinical Trials Unit at University College London, London, UK.
J Antimicrob Chemother. 2019 Mar 1;74(3):746-753. doi: 10.1093/jac/dky468.
In subjects with transmitted thymidine analogue mutations (TAMs), boosted PIs (PI/b) are often chosen to overcome possible resistance to the NRTI backbone. However, data to guide treatment selection are limited. Our aim was to obtain firmer guidance for clinical practice using real-world cohort data.
We analysed 1710 subjects who started a PI/b in combination with tenofovir or abacavir plus emtricitabine or lamivudine, and compared their virological outcomes with those of 4889 patients who started an NNRTI (predominantly efavirenz), according to the presence of ≥1 TAM as the sole form of transmitted drug resistance.
Participants with ≥1 TAM comprised predominantly MSM (213 of 269, 79.2%), subjects of white ethnicity (206 of 269, 76.6%) and HIV-1 subtype B infections (234 of 269, 87.0%). Most (203 of 269, 75.5%) had singleton TAMs, commonly a revertant of T215Y or T215F (112 of 269, 41.6%). Over a median of 2.5 years of follow-up, 834 of 6599 (12.6%) subjects experienced viraemia (HIV-1 RNA >50 copies/mL). The adjusted HR for viraemia was 2.17 with PI/b versus NNRTI-based therapy (95% CI 1.88-2.51; P < 0.001). Other independent predictors of viraemia included injecting drug use, black ethnicity, higher viral load and lower CD4 cell count at baseline, and receiving abacavir instead of tenofovir. Resistance showed no overall impact (adjusted HR 0.77 with ≥1 TAM versus no resistance; 95% CI 0.54-1.10; P = 0.15).
In this cohort, patients harbouring ≥1 TAM as the sole form of transmitted drug resistance gained no apparent virological advantage from starting first-line ART with a PI/b.
在携带胸腺嘧啶核苷类似物突变（TAMs）的受试者中，通常选择强化蛋白酶抑制剂（PI/b）来克服对核苷逆转录酶抑制剂（NRTI）骨干药物的可能耐药性。然而，指导治疗选择的数据有限。我们的目的是使用真实世界的队列数据为临床实践提供更可靠的指导。
我们分析了 1710 名开始接受 PI/b 联合替诺福韦或阿巴卡韦加恩曲他滨或拉米夫定治疗的受试者，并根据是否存在≥1 种 TAM 作为唯一形式的传播性耐药性，将他们的病毒学结果与 4889 名开始接受非核苷逆转录酶抑制剂（主要为依非韦伦）治疗的患者进行了比较。
≥1 种 TAM 的参与者主要为男男性行为者（269 例中的 213 例，79.2%）、白种人（269 例中的 206 例，76.6%）和 HIV-1 亚型 B 感染者（269 例中的 234 例，87.0%）。大多数（269 例中的 203 例，75.5%）仅有单一 TAMs，通常是 T215Y 或 T215F 的回复突变（269 例中的 112 例，41.6%）。在中位随访 2.5 年期间，6599 名受试者中有 834 名（12.6%）发生病毒血症（HIV-1 RNA>50 拷贝/mL）。与 NNRTI 为基础的治疗相比，PI/b 治疗的病毒血症调整后的 HR 为 2.17（95%CI 1.88-2.51；P<0.001）。病毒血症的其他独立预测因素包括注射吸毒、黑种人、基线时更高的病毒载量和更低的 CD4 细胞计数，以及接受阿巴卡韦而非替诺福韦。耐药性总体上没有影响（调整后的 HR 0.77，≥1 种 TAM 与无耐药性相比；95%CI 0.54-1.10；P=0.15）。
在本队列中，作为唯一形式的传播性耐药性携带≥1 种 TAMs 的患者，从一线抗逆转录病毒治疗开始使用 PI/b 并没有获得明显的病毒学优势。
