Torti Carlo, Lapadula Giuseppe, Barreiro Pablo, Soriano Vicente, Mandalia Sundhiya, De Silvestri Annalisa, Suter Fredy, Maggiolo Franco, Antinori Andrea, Antonucci Francesco, Maserati Renato, El Hamad Issa, Pierotti Piera, Sighinolfi Laura, Migliorino Guglielmo, Ladisa Nicoletta, Carosi Giampiero
Università degli Studi di Brescia, p le Spedali Civili 1, Brescia, Italy.
J Antimicrob Chemother. 2007 Jun;59(6):1141-7. doi: 10.1093/jac/dkm100. Epub 2007 Apr 13.
Tenofovir with full-dose didanosine has been associated with paradoxical CD4 + T cell decrease despite virological suppression. We investigated whether tenofovir plus didanosine at a weight-adjusted dosage could be responsible for such an effect, and factors associated with CD4 + T cell count evolution under this combination.
This was a prospective observational multicohort study (Italian MASTER and Spanish Hospital Carlos III HIV cohorts). Patients with HIV plasma viral load suppression for >/= 6 months who switched to an antiretroviral combination including tenofovir plus didanosine were studied, as long as virological success was maintained. CD4 + T cell count variations over time (slopes) were compared before and after switching to tenofovir plus didanosine using linear mixed models and segmented regression analysis.
Annual time-weighted CD4 + T cell count slope did not change significantly after the prescription of tenofovir plus didanosine: it was 14 cells/mm(3) [95% confidence interval (CI) - 7 to 35] from month - 24 to month - 12, 12 cells/mm(3) (95% CI - 14 to 38) from month - 12 to the time of switching, 30 cells/mm(3) (95% CI 5-55) from switching to month + 12 and 15 cells/mm(3) (95% CI - 8 to 39) from month + 12 to month + 24 after switching to tenofovir plus didanosine. No significant change in the slope of the segment after the switch to tenofovir plus didanosine-containing regimens when compared with the segment preceding the intervention was found (CD4 + T cell count slope change: 24 cells/mm(3); 95% CI - 10 to 58). Similar results were obtained using CD4 + T cell percentage over total lymphocytes. The significant independent predictors of lower CD4 + T cell count slope were older age (P = 0.006), lower nadir CD4 + T cell count (P < 0.001) and positive hepatitis C virus antibody (P = 0.03). Moreover, reduced estimated creatinine clearance was an additional independent predictor of lower CD4 + T cell count slope (P = 0.02), but only after excluding nadir CD4 + T cell count.
Tenofovir plus didanosine (weight-adjusted dosage) was not associated with paradoxical CD4 + T cell decrease in our patients maintaining undetectable HIV plasma viral load for a maximum of 24 months after switching. Several factors could explain variability in CD4 + T cell count evolution in these patients.
尽管病毒学得到抑制，但替诺福韦与全剂量去羟肌苷联用曾与CD4+T细胞计数反常下降有关。我们调查了按体重调整剂量的替诺福韦加去羟肌苷是否会导致这种效应，以及在此联合用药情况下与CD4+T细胞计数变化相关的因素。
这是一项前瞻性观察性多队列研究（意大利MASTER队列和西班牙卡洛斯三世医院HIV队列）。研究了血浆病毒载量抑制≥6个月且改用包括替诺福韦加去羟肌苷的抗逆转录病毒联合方案的HIV患者，前提是维持病毒学成功。使用线性混合模型和分段回归分析比较改用替诺福韦加去羟肌苷前后CD4+T细胞计数随时间的变化（斜率）。
使用替诺福韦加去羟肌苷治疗后，年度时间加权CD4+T细胞计数斜率无显著变化：从第-24个月到第-12个月为14个细胞/mm³[95%置信区间（CI）-7至35]，从第-12个月到换药时为12个细胞/mm³（95%CI-14至38），从换药到第+12个月为30个细胞/mm³（95%CI5-55），改用替诺福韦加去羟肌苷后从第+12个月到第+24个月为15个细胞/mm³（95%CI-8至39）。与干预前阶段相比，改用含替诺福韦加去羟肌苷方案后阶段的斜率无显著变化（CD4+T细胞计数斜率变化：24个细胞/mm³；95%CI-10至58）。使用CD4+T细胞占总淋巴细胞的百分比也得到了类似结果。CD4+T细胞计数斜率较低的显著独立预测因素为年龄较大（P=0.006）、最低CD4+T细胞计数较低（P<0.001）和丙型肝炎病毒抗体阳性（P=0.03）。此外，估计肌酐清除率降低是CD4+T细胞计数斜率较低的另一个独立预测因素（P=0.02），但仅在排除最低CD4+T细胞计数后。
在我们的患者中，改用替诺福韦加去羟肌苷（按体重调整剂量）与CD4+T细胞计数反常下降无关，这些患者在换药后最多24个月内HIV血浆病毒载量一直无法检测到。有几个因素可以解释这些患者CD4+T细胞计数变化的变异性。
