Bruyand Mathias, Ryom Lene, Shepherd Leah, Fatkenheuer Gerd, Grulich Andrew, Reiss Peter, de Wit Stéphane, D Arminio Monforte Antonella, Furrer Hansjakob, Pradier Christian, Lundgren Jens, Sabin Caroline
*INSERM, ISPED, Centre Inserm U897-Epidemiologie-Biostatistique, Bordeaux, France; †Copenhagen HIV Programme, Department of Infectious Diseases and Rheumatology, Section 8632, Finsencenteret, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; ‡Research Department of Infection and Population Health, UCL, London, United Kingdom; §First Department of Internal Medicine, University Hospital of Cologne, Köln, Germany; ‖German Center for Infection research (DZIF); ¶HIV Epidemiology and Prevention Program, Kirby Institute, UNSW Australia, Sydney, Australia; #Division of Infectious Diseases and Department of Global Health, Amsterdam Institute for Global Health and Development, Academic Medical Center, Amsterdam, the Netherlands; **Stichting HIV Monitoring, Amsterdam, the Netherlands; ††Department of Infectious Diseases, St Pierre University Hospital, Brussels, Belgium; ‡‡Infectious Diseases Unit, Department of Health Sciences, San Paolo University Hospital, Milan, Italy; §§Department of Infectious Diseases, Bern University Hospital and University of Bern, Bern, Switzerland; and ‖‖Département de Santé Publique, Hôpital de l'Archet, CHU de Nice, Nice, France.
J Acquir Immune Defic Syndr. 2015 Apr 15;68(5):568-77. doi: 10.1097/QAI.0000000000000523.
The association between combination antiretroviral therapy (cART) and cancer risk, especially regimens containing protease inhibitors (PIs) or nonnucleoside reverse transcriptase inhibitors (NNRTIs), is unclear.
Participants were followed from the latest of D:A:D study entry or January 1, 2004, until the earliest of a first cancer diagnosis, February 1, 2012, death, or 6 months after the last visit. Multivariable Poisson regression models assessed associations between cumulative (per year) use of either any cART or PI/NNRTI, and the incidence of any cancer, non-AIDS-defining cancers (NADC), AIDS-defining cancers (ADC), and the most frequently occurring ADC (Kaposi sarcoma, non-Hodgkin lymphoma) and NADC (lung, invasive anal, head/neck cancers, and Hodgkin lymphoma).
A total of 41,762 persons contributed 241,556 person-years (PY). A total of 1832 cancers were diagnosed [incidence rate: 0.76/100 PY (95% confidence interval: 0.72 to 0.79)], 718 ADC [0.30/100 PY (0.28-0.32)], and 1114 NADC [0.46/100 PY (0.43-0.49)]. Longer exposure to cART was associated with a lower ADC risk [adjusted rate ratio: 0.88/year (0.85-0.92)] but a higher NADC risk [1.02/year (1.00-1.03)]. Both PI and NNRTI use were associated with a lower ADC risk [PI: 0.96/year (0.92-1.00); NNRTI: 0.86/year (0.81-0.91)]. PI use was associated with a higher NADC risk [1.03/year (1.01-1.05)]. Although this was largely driven by an association with anal cancer [1.08/year (1.04-1.13)], the association remained after excluding anal cancers from the end point [1.02/year (1.01-1.04)]. No association was seen between NNRTI use and NADC [1.00/year (0.98-1.02)].
Cumulative use of PIs may be associated with a higher risk of anal cancer and possibly other NADC. Further investigation of biological mechanisms is warranted.
联合抗逆转录病毒疗法（cART）与癌症风险之间的关联尚不清楚，尤其是包含蛋白酶抑制剂（PI）或非核苷类逆转录酶抑制剂（NNRTI）的治疗方案。
从D:A:D研究最新入组时间或2004年1月1日起对参与者进行随访，直至首次癌症诊断、2012年2月1日死亡、末次随访后6个月这三者中最早发生的事件。多变量泊松回归模型评估了每年使用任何cART或PI/NNRTI的累积使用情况与任何癌症、非艾滋病定义性癌症（NADC）、艾滋病定义性癌症（ADC）以及最常见的ADC（卡波西肉瘤、非霍奇金淋巴瘤）和NADC（肺癌、浸润性肛门癌、头/颈部癌和霍奇金淋巴瘤）发病率之间的关联。
共有41,762人贡献了241,556人年（PY）。共诊断出1832例癌症[发病率：0.76/100 PY（95%置信区间：0.72至0.79）]，718例ADC[0.30/100 PY（0.28 - 0.32）]，以及1114例NADC[0.46/100 PY（0.43 - 0.49）]。长期接受cART治疗与较低的ADC风险相关[校正率比：0.88/年（0.85 - 0.92）]，但与较高的NADC风险相关[1.02/年（1.00 - 1.03）]。使用PI和NNRTI均与较低的ADC风险相关[PI：0.96/年（0.92 - 1.00）；NNRTI：0.86/年（0.81 - 0.91）]。使用PI与较高的NADC风险相关[1.03/年（1.01 - 1.05）]。尽管这在很大程度上是由与肛门癌的关联所驱动[1.08/年（1.04 - 1.13）]，但在将肛门癌从终点中排除后，这种关联仍然存在[1.02/年（1.01 - 1.04）]。未观察到使用NNRTI与NADC之间存在关联[1.00/年（0.98 - 1.02）]。
PI的累积使用可能与肛门癌以及可能的其他NADC的较高风险相关。有必要对生物学机制进行进一步研究。
