Sub-Saharan African countries are transitioning to dolutegravir-based regimens, even for patients with extensive previous drug exposure, including first-generation integrase strand-transfer inhibitors (INSTI) such as raltegravir. Such exposure might have implications on cross-resistance to dolutegravir-based antiretroviral therapies (ART). We report a 65 years old Cameroonian, previously exposed to raltegravir, and failing on third-line treatment with multi-drug resistance to darunavir/r and dolutegravir. Genotypic resistance testing (GRT) and viral tropism were performed during monitoring time points. The patient initiated ART in August 2007. At the time point of the first (29.04.2010), second (01.12.2017) and third (08.08.2019) GRT, prior ART exposure included 3TC, d4T, NVP and EFV; additionally TDF, DRV/r and RAL; and additionally ABC and DTG respectively. First GRT revealed mutations associated with resistance only to first-generation Non-nucleoside reverse transcriptase inhibitors (NNRTI). Second GRT revealed mutations associated with high-level resistance to all NRTIs, first generation NNRTIs, all ritonavir boosted protease inhibitors (PI/r), and all INSTI, while viral tropism (using geno2pheno) revealed a CCR5-tropic virus with a false positive rate (FPR) of 60.9% suggesting effectiveness of maraviroc (MRV). The third GRT showed high-level resistance to NRTI, NNRTI, all PI and all INSTI, with additional mutations (H221HY for NNRTI and S147G for INSTI), and a CCR5-tropic virus with a slightly reduced FPR (57.0%). Without any locally available active therapeutic option, the patient has been on a maintenance therapy with “DRV/r (600mg x 2/day)+TDF+3TC” and patient/family-centered adherence has been reinforced. Since the first viral load (VL) measurement in 2010, the patient has had 12 VL tests with the VL ranging from 4.97 Log to 6.44 Log copies/mL and the CD4 count never exceeded 200 cells/μL. As African countries transition to dolutegravir-based regimens, prior raltegravir-exposure may prompt selection (and potential transmission) of dolutegravir-resistance, supporting case surveillance.

中文翻译：

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喀麦隆接触 Raltegravir 后首例 Dolutegravir 和 Darunavir/r 多药耐药 HIV-1：过渡到基于 Dolutegravir 的方案时代的教训和影响。

撒哈拉以南非洲国家正在过渡到基于 dolutegravir 的治疗方案，即使对于先前广泛接触药物的患者，包括第一代整合酶链转移抑制剂 (INSTI)，如拉替拉韦。这种暴露可能对基于多替拉韦的抗逆转录病毒疗法 (ART) 的交叉耐药性产生影响。我们报告了一名 65 岁的喀麦隆人，之前曾接触过拉替拉韦，但在三线治疗中失败，对达芦那韦/r 和多替拉韦产生多重耐药性。在监测时间点期间进行基因型抗性测试 (GRT) 和病毒嗜性。患者于 2007 年 8 月开始接受 ART。在第一次 (29.04.2010)、第二次 (01.12.2017) 和第三次 (08.08.2019) GRT 的时间点，先前的 ART 暴露包括 3TC、d4T、NVP 和 EFV；另外 TDF、DRV/r 和 RAL；另外还有ABC和DTG。第一次 GRT 揭示了仅与对第一代非核苷逆转录酶抑制剂 (NNRTI) 的抗性相关的突变。第二次 GRT 揭示了与对所有 NRTI、第一代 NNRTI、所有利托那​​韦增强蛋白酶抑制剂 (PI/r) 和所有 INSTI 的高水平耐药性相关的突变，而病毒嗜性（使用 geno2pheno）揭示了 CCR5 嗜性病毒的假阳性率 (FPR) 为 60.9%，表明 maraviroc (MRV) 的有效性。第三个 GRT 显示对 NRTI、NNRTI、所有 PI 和所有 INSTI 的高水平抗性，具有额外的突变（NNRTI 的 H221HY 和 INSTI 的 S147G），以及 FPR 略微降低（57.0%）的 CCR5 嗜性病毒。没有任何当地可用的积极治疗选择，患者一直在接受“DRV/r（600mg x 2/天）+TDF+3TC”的维持治疗，并加强了以患者/家庭为中心的依从性。自 2010 年第一次病毒载量 (VL) 测量以来，患者已进行了 12 次 VL 测试，VL 范围从 4.97 Log 到 6.44 Log 拷贝/mL，CD4 计数从未超过 200 个细胞/μL。随着非洲国家过渡到基于 dolutegravir 的方案，先前的 raltegravir 暴露可能会促使选择（和潜在的传播）多替拉韦耐药性，从而支持病例监测。