Department of Biomedical and Clinical Sciences, DIBIC Luigi Sacco, Milan University, Via G.B. Grassi 74, 20157, Milan, Italy.
III Infectious Disease Unit, ASST Fatebenefratelli Sacco University Hospital, Milan, Italy.
BMC Infect Dis. 2020 Apr 7;20(1):273. doi: 10.1186/s12879-020-04999-4.
Syphilis has been associated with an increase in HIV RNA and a temporary decline in CD4 T cell counts in people living with HIV who are not receiving antiretroviral treatment (ART), and may be associated with a transient HIV RNA rebound in those who are receiving ART. Our case is the first to highlight the risk of a multidrug-resistant HIV viral rebound during the course of early syphilis even if antiretroviral drug concentrations are within the therapeutic range.
This 50-year-old HIV-1-positive male patient with concomitant early syphilis presented with an HIV RNA rebound (8908 copies/mL) during a scheduled visit to our clinic. He was receiving a stable ART regimen consisting of darunavir/cobicistat plus dolutegravir, and had a 15-year history of viral suppression. Good short-term drug adherence could be inferred as liquid chromatography tandem mass spectrometry showed that his trough antiretroviral drug concentrations were within the therapeutic range: darunavir 2353 ng/mL (minimum effective concentration > 500 ng/mL) and dolutegravir 986 ng/mL (minimum effective concentration > 100 ng/mL). A plasma RNA genotype resistance test revealed wild-type virus in the integrase region and protease region (PR), but extensive resistance in the reverse transcriptase (RT) region (M41L, E44D, D67N, K70R, M184V, L210W and T215Y). Phylogenetic analysis of next-generation sequences (used to investigate the presence of minor viral variants), the PR and RT sequences from plasma HIV RNA and pro-viral DNA extracted from peripheral blood mononuclear cells during the viral rebound, and a Sanger sequence obtained during a previous virological failure suggested clonal viral expression because the previous PR resistance mutations had been lost or had not been archived in pro-viral DNA.
This case shows that early syphilis may cause an HIV RNA rebound in patients under stable virological control with the potential of transmitting an extensively drug-resistant virus.
梅毒可使未接受抗逆转录病毒治疗（ART）的 HIV 感染者的 HIV RNA 增加，CD4 T 细胞计数暂时下降，并且可能与正在接受 ART 的患者的 HIV RNA 短暂反弹有关。我们的病例首次强调了即使在抗逆转录病毒药物浓度在治疗范围内的情况下，早期梅毒过程中也可能存在耐药性 HIV 病毒反弹的风险。
这名 50 岁 HIV-1 阳性男性合并早期梅毒，在我院就诊时 HIV RNA 反弹（8908 拷贝/毫升）。他正在接受稳定的 ART 方案治疗，包括达芦那韦/考比司他加度鲁特韦，且病毒抑制已有 15 年的历史。液相色谱串联质谱法显示他的药物谷浓度在治疗范围内，可推断其短期药物依从性良好：达芦那韦 2353ng/ml（最低有效浓度>500ng/ml）和度鲁特韦 986ng/ml（最低有效浓度>100ng/ml）。血浆 RNA 基因型耐药检测显示整合酶区和蛋白酶区（PR）为野生型病毒，但逆转录酶（RT）区存在广泛耐药（M41L、E44D、D67N、K70R、M184V、L210W 和 T215Y）。下一代序列的系统进化分析（用于检测次要病毒变异体的存在）、病毒反弹期间从血浆 HIV RNA 和外周血单个核细胞中提取的前病毒 DNA 中的 PR 和 RT 序列以及之前病毒学失败时获得的 Sanger 序列表明存在克隆病毒表达，因为之前的 PR 耐药突变已丢失或未在前病毒 DNA 中存档。
本病例表明，早期梅毒可能导致稳定病毒学控制的患者 HIV RNA 反弹，并可能传播耐药性广泛的病毒。
