Benhammou Valérie, Warszawski Josiane, Bellec Stéphanie, Doz François, André Nicolas, Lacour Brigitte, Levine Martine, Bavoux Françoise, Tubiana Roland, Mandelbrot Laurent, Clavel Jacqueline, Blanche Stéphane
Inserm, U822, Le Kremlin-Bicêtre, France.
AIDS. 2008 Oct 18;22(16):2165-77. doi: 10.1097/QAD.0b013e328311d18b.
Long-term studies of tolerance to perinatal exposure to antiretroviral nucleoside reverse transcriptase inhibitors are required, in view of the potential genotoxicity of some of these molecules.
To evaluate the incidence of cancers in uninfected children born to HIV-infected mothers.
Cancers were detected in a nationwide prospective cohort of children born to HIV-infected mothers by standardized questionnaire during the prospective follow-up period of 2 years; thereafter, they were detected by spontaneous pharmacovigilance declaration and by crosschecking data with the national registries of childhood cancer. Standardized incidence ratio for incidence comparisons with general population.
Ten cases of cancer were detected among the 9127 exposed HIV-uninfected children (median age: 5.4 years, 53 052 person-years of follow-up). The overall incidence did not differ significantly from that expected for the general population: 10 cases observed versus 8.9 and 9.6 expected depending on whether 1990-1999 or 2000-2004 national rates were used as reference [standardized incidence ratio of 1.1 (0.3-1.5) and 1.0 (0.5-1.9)]. Five cases of central nervous system cancer were observed (standardized incidence ratio of 3.1 [1.0-7.2] P = 0.05 and 2.4 [0.8-5.6], P = 0.12). The relative risk of cancer for children exposed to didanosine-lamivudine combination was higher than that for zidovudine monotherapy [hazard ratio: 13.6 (2.5-73.9)].
This study did not evidence an overall increase in cancer risk in nucleoside reverse transcriptase inhibitor exposed children until 5 years of age. Results suggesting associations with specific nucleoside reverse transcriptase inhibitor combinations need further investigations. A longer surveillance, including differential analysis of the different cancer sites and various nucleoside reverse transcriptase inhibitors administered is warranted.
鉴于某些抗逆转录病毒核苷类逆转录酶抑制剂具有潜在的遗传毒性，需要对围产期接触此类药物的耐受性进行长期研究。
评估感染HIV的母亲所生未感染儿童的癌症发病率。
在一项全国性的前瞻性队列研究中，通过标准化问卷在为期2年的前瞻性随访期间对感染HIV的母亲所生儿童进行癌症检测；此后，通过自发的药物警戒申报以及与国家儿童癌症登记处的数据交叉核对来进行检测。采用标准化发病率比与一般人群进行发病率比较。
在9127名暴露于HIV但未感染的儿童中检测到10例癌症（中位年龄：5.4岁，随访53052人年）。总体发病率与一般人群预期发病率无显著差异：根据以1990 - 1999年还是2000 - 2004年的全国发病率为参考，观察到10例，预期分别为8.9例和9.6例[标准化发病率比分别为1.1(0.3 - 1.5)和1.0(0.5 - 1.9)]。观察到5例中枢神经系统癌症（标准化发病率比分别为3.1[1.0 - 7.2]，P = 0.05和2.4[0.8 - 5.6]，P = 0.12）。接受去羟肌苷 - 拉米夫定联合治疗的儿童患癌相对风险高于齐多夫定单药治疗[风险比：13.6(2.5 - 73.9)]。
本研究未证明暴露于核苷类逆转录酶抑制剂的儿童在5岁前患癌风险总体增加。提示与特定核苷类逆转录酶抑制剂联合用药有关联的结果需要进一步研究。有必要进行更长时间的监测，包括对不同癌症部位和所使用的各种核苷类逆转录酶抑制剂进行差异分析。
