Soh Chang-Heok, Oleske James M, Brady Michael T, Spector Stephen A, Borkowsky William, Burchett Sandra K, Foca Marc D, Handelsman Edward, Jiménez Eleanor, Dankner Wayne M, Hughes Michael D
Department of Biostatistics, Harvard School of Public Health, MA, Boston 02115, USA
Lancet. 2003 Dec 20;362(9401):2045-51. doi: 10.1016/s0140-6736(03)15098-2.
There is limited evidence about longer-term effects of combination antiretroviral therapy that includes protease inhibitors (PIs) on the immunological status of HIV-1-infected children. Better understanding might help to resolve questions on when to initiate treatment.
The change in percentage of CD4-positive T lymphocytes (CD4%) was investigated in 1012 previously treated HIV-1-infected children (aged 0-17 years) who were enrolled in research clinics in the USA before 1996 and followed up to 2000. 702 started PI-based combination therapy. Data analyses ignored subsequent treatment changes.
Among the 1012 children, the median CD4% increased from 22% to 28% between 1996, when PIs were first prescribed, and 2000. For the 702 who started PI-based therapy, the mean CD4% increase after 3 years was largest among participants with the greatest immunosuppression (15.7%, 10.6%, 5.1%, and 2.0% for participants with CD4% before therapy of <5%, 5-14%, 15-24%, and >25%; p<0.0001). After adjustment for pre-PI CD4%, the mean increase was largest among the youngest participants (9.2%, 8.0%, and 4.3% for ages <5 years, 5-9 years, and >10 years; p=0.001). However, only a minority of significantly immunocompromised participants (33%, 26%, and 49% of those with pre-PI CD4% of <5%, 5-14%, or 15-24%) achieved CD4% values above 25%, whereas 84% of those with pre-PI values above 25% maintained such values.
Although PI-based therapy was associated with substantial improvements in CD4%, initiation before severe immunosuppression and at younger ages may be more effective for recovery or maintenance of normal CD4%. Randomised investigation of when to start combination therapy in children, particularly infants, is needed.
关于包含蛋白酶抑制剂（PIs）的联合抗逆转录病毒疗法对HIV-1感染儿童免疫状态的长期影响，证据有限。更好地了解这一点可能有助于解决何时开始治疗的问题。
对1996年以前在美国研究诊所登记入组、截至2000年进行随访的1012名曾接受治疗的HIV-1感染儿童（年龄0至17岁）的CD4阳性T淋巴细胞百分比（CD4%）变化进行了研究。702名儿童开始接受基于蛋白酶抑制剂的联合疗法。数据分析未考虑后续治疗变化。
在这1012名儿童中，1996年首次开具蛋白酶抑制剂处方至2000年间，CD4%中位数从22%升至28%。对于开始基于蛋白酶抑制剂治疗的702名儿童，治疗3年后，免疫抑制最严重的参与者CD4%平均增幅最大（治疗前CD4%<5%、5-14%、15-24%和>25%的参与者，增幅分别为15.7%、10.6%、5.1%和2.0%；p<0.0001）。在调整治疗前CD4%后，最年幼的参与者平均增幅最大（年龄<5岁、5-9岁和>10岁的参与者，增幅分别为9.2%、8.0%和4.3%；p=0.001）。然而，只有少数免疫功能严重受损的参与者（治疗前CD4%<5%、5-14%或15-24%的参与者中，分别有33%、26%和49%）CD4%值达到25%以上，而治疗前CD4%值高于25%的参与者中，84%维持了该水平。
虽然基于蛋白酶抑制剂的疗法与CD4%的显著改善相关，但在严重免疫抑制之前且年龄较小的时候开始治疗，对于恢复或维持正常CD4%可能更有效。需要对儿童尤其是婴儿何时开始联合治疗进行随机研究。
