Imaz Arkaitz, García Federico, di Yacovo Silvana, Llibre Josep M
Unidad de VIH, Servicio de Enfermedades Infecciosas, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, España.
Enferm Infecc Microbiol Clin. 2013 Jun;31 Suppl 2:36-43. doi: 10.1016/S0213-005X(13)70141-1.
Rilpivirine (RPV) is a new second-generation nonnucleoside reverse transcriptase inhibitor (NNRTI) approved for use in combination with two nucleoside/nucleotide reverse transcriptase inhibitors (NRTI) as initial therapy in treatment-naïve HIV-1-infected patients with a baseline viral load ≤100,000 copies/mL. RPV is a diarylpyrimidine derivative with potent in vitro activity against multiple HIV-1 variants with resistance mutations to first-generation NNRTI such as K103N. In vitro studies and phase III clinical trials have allowed the identification of 16 mutations associated with resistance to RPV K101E/P, E138A/G/K/Q/R, V179L, Y181C/I/V, Y188L, H221Y, F227C and M230I/L. The risk of virologic failure in patients receiving RPV plus 2 NRTI with plasma viral load ≤ 100,000 copies/mL is low, but a high percentage of patients failing RPV develop resistance mutations to both RPV and NRTI. The most common resistance mutation that emerges in this setting is E138K. This mutation is usually associated with M184I due to a double compensatory effect of this combination, which confers resistance to RPV, as well as to lamivudine and emtricitabine. The emergence of RPV resistance confers cross-resistance to all NNRTI and, importantly, high percentages of cross-resistance to etravirine.
利匹韦林（RPV）是一种新型第二代非核苷类逆转录酶抑制剂（NNRTI），被批准与两种核苷类/核苷酸类逆转录酶抑制剂（NRTI）联合使用，作为初始治疗方案，用于治疗初治的、基线病毒载量≤100,000拷贝/mL的HIV-1感染患者。RPV是一种二芳基嘧啶衍生物，对多种对第一代NNRTI（如K103N）产生耐药突变的HIV-1变体具有强大的体外活性。体外研究和III期临床试验已确定了16种与对RPV耐药相关的突变：K101E/P、E138A/G/K/Q/R、V179L、Y181C/I/V、Y188L、H221Y、F227C和M230I/L。接受RPV加2种NRTI治疗且血浆病毒载量≤100,000拷贝/mL的患者发生病毒学失败的风险较低，但接受RPV治疗失败的患者中有很大比例会对RPV和NRTI都产生耐药突变。在这种情况下出现的最常见耐药突变是E138K。由于这种组合的双重补偿作用，该突变通常与M184I相关，这赋予了对RPV以及拉米夫定和恩曲他滨的耐药性。RPV耐药的出现会导致对所有NNRTI产生交叉耐药，重要的是，对依曲韦林也有很高比例的交叉耐药。
