Sarmati Loredana, Parisi Saverio Giuseppe, Nicastri Emanuele, d'Ettorre Gabriella, Andreoni Carolina, Dori Luca, Gatti Francesca, Montano Marco, Buonomini Anna Rita, Boldrin Caterina, Palù Giorgio, Vullo Vincenzo, Andreoni Massimo
Department of Public Health and Cellular Biology, University of Rome Tor Vergata, Rome, Italy.
J Med Virol. 2007 Jul;79(7):880-6. doi: 10.1002/jmv.20914.
Simplified regimens containing protease-inhibitors (PI)-sparing combinations were used in patients with virological suppression after prolonged highly active antiretroviral therapy. This study evaluated the total HIV-1 DNA quantitation as a predictor of long-term success for PI-sparing simplified therapy. Sixty-two patients were enrolled in a prospective non-randomized cohort. All patients have been receiving a triple-therapy regimen, two nucleoside reverse transcriptase inhibitors (NRTIs) plus one PI, for at least 9 months and were characterized by undetectable plasma HIV-1 RNA levels (<50 cp/ml) for at least 6 months. Patients were changed to a simplified PI-sparing regimen to overcome PI-associated adverse effects. HIV-DNA levels in peripheral blood mononuclear cells (PBMCs) were evaluated at baseline and at the end of follow-up. Patients with proviral DNA levels below the median value (226 copies/10(6) PBMCs) had a significant higher CD4 cell count at nadir (P = 0.003) and at enrolment (P = 0.001) with respect to patients with HIV-DNA levels above the median value. At month 18, 53 out of 62 (85%) patients on simplified regimen showed virological success, 4 (6.4%) patients experienced virological failure and 5 (8%) patients showed viral blip. At logistic regression analysis, HIV-DNA levels below 226 copies/10(6) PBMCs at baseline were associated independently to a reduced risk of virological failure or viral blip during simplified therapy (OR 0.002, 95% CI 0.001-0.46, P = 0.025). The substitution of PI with NRTI or non-NRTIs may represent an effective treatment option. Indeed, treatment failure or viral blip were experienced by 6% and 8% of the patients on simplified therapy, respectively. In addition, sustained suppression of the plasma viral load was significantly correlated with low levels of proviral DNA before treatment simplification.
对于在长期高效抗逆转录病毒治疗后实现病毒学抑制的患者，使用了含蛋白酶抑制剂（PI）简化组合的治疗方案。本研究评估了总HIV-1 DNA定量作为PI简化治疗长期成功预测指标的价值。62例患者纳入一项前瞻性非随机队列研究。所有患者均接受三联疗法，即两种核苷类逆转录酶抑制剂（NRTIs）加一种PI，至少9个月，且血浆HIV-1 RNA水平至少6个月检测不到（<50拷贝/毫升）。为克服PI相关的不良反应，患者改为简化的不含PI方案。在基线和随访结束时评估外周血单个核细胞（PBMC）中的HIV-DNA水平。与HIV-DNA水平高于中位数的患者相比，前病毒DNA水平低于中位数（226拷贝/10⁶ PBMC）的患者在最低点时（P = 0.003）和入组时（P = 0.001）的CD4细胞计数显著更高。在第18个月时，62例接受简化方案治疗的患者中有53例（85%）实现病毒学成功，4例（6.4%）患者经历病毒学失败，5例（8%）患者出现病毒学波动。在逻辑回归分析中，基线时HIV-DNA水平低于226拷贝/10⁶ PBMC与简化治疗期间病毒学失败或病毒学波动风险降低独立相关（比值比0.002，95%置信区间0.001 - 0.46，P = 0.025）。用NRTI或非NRTI替代PI可能是一种有效的治疗选择。实际上，简化治疗的患者分别有6%和8%经历治疗失败或病毒学波动。此外，血浆病毒载量的持续抑制与治疗简化前前病毒DNA低水平显著相关。
