Division of Allergy and Clinical Immunology, Department of Medicine, University of Cape Town.
Allergy and Immunology Unit, University of Cape Town Lung Institute.
Curr Opin Allergy Clin Immunol. 2019 Aug;19(4):272-282. doi: 10.1097/ACI.0000000000000545.
Immune-mediated adverse drug reactions (IM-ADRs) are many times more common in HIV-infected patients. Usual offending drugs include antiretroviral and antiinfectives, but the burden of specific drug IM-ADRs is population-specific; changing as new and fixed dose combinations enter the market, and drug-resistance patterns demand. This review considers recent literature on epidemiology, mechanisms, clinical management and prevention of IM-ADRs amongst persons living with HIV/AIDS.
Epidemiological studies continue to describe high rates of delayed hypersensitivity to known offenders, as well as similar reactions in preexposure prophylaxis. IM-ADRs to oral and injectable integrase strand transfer inhibitors are reported with expanding use. The clinical spectrum and management of IM-ADRs occurring in HIV-infected populations is similar to uninfected; with exceptions such as a recently described severe delayed efavirenz DILI with high mortality. Furthermore, the context can be unique, such as the lower than expected mortality in a Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) cohort from a HIV/TB high burden setting. Programmatic data showing the near complete elimination of Abacavir drug hypersensitivity syndrome following implementation of HLA-B57:01 screening is a stellar example of how prevention is possible with mechanistic insight.
IM-ADRs remain a challenge in persons living with HIV. The complexities posed by polypharmacy, overlapping drug toxicities, drug interactions, overlap of IM-ADRs with other diseases, limited alternative drugs, and vulnerable patients with advanced immunosuppression with high mortality, necessitate increased use of drug provocation testing, treat-through and desensitization strategies. There is an urgent need for improved diagnostics and predictive biomarkers for prevention, or to guide treat-through, rechallenge and desensitization approaches.
免疫介导的药物不良反应（IM-ADR）在 HIV 感染者中更为常见。常见的致病药物包括抗逆转录病毒药物和抗感染药物，但特定药物 IM-ADR 的负担因人群而异；随着新的和固定剂量组合进入市场，以及耐药模式的需求，这一负担正在发生变化。本文综述了最近关于 HIV 感染者中 IM-ADR 的流行病学、机制、临床管理和预防的文献。
流行病学研究继续描述了对已知致病药物迟发性超敏反应的高发生率，以及在暴露前预防中也有类似的反应。随着整合酶链转移抑制剂的口服和注射制剂的广泛应用，其 IM-ADR 也有报道。发生在 HIV 感染者中的 IM-ADR 的临床谱和管理与未感染者相似；但也有例外，如最近描述的严重延迟型依非韦伦肝毒性，死亡率较高。此外，情况可能是独特的，例如在 HIV/TB 负担较重的环境中，史蒂文斯-约翰逊综合征和中毒性表皮坏死松解症（SJS/TEN）队列的死亡率低于预期。方案数据显示，在实施 HLA-B57:01 筛查后，阿巴卡韦药物超敏反应综合征的发生率几乎完全消除，这是一个很好的例子，说明了如何通过机制洞察来实现预防。
IM-ADR 仍然是 HIV 感染者面临的挑战。多药治疗、重叠药物毒性、药物相互作用、IM-ADR 与其他疾病的重叠、替代药物有限以及晚期免疫抑制、死亡率高的脆弱患者等复杂性，需要增加药物激发试验、治疗性药物暴露和脱敏策略的应用。迫切需要改进诊断和预测生物标志物，以预防或指导治疗性药物暴露、再挑战和脱敏方法。
