Lillo F, Grasso M, Lodini S, Capiluppi B, Lazzarin A, Tambussi G
Laboratory of Virology, Scientific Institute San Raffaele, Milan, Italy.
J Biol Regul Homeost Agents. 2002 Jan-Mar;16(1):49-52.
HIV-1 reservoir is early established during PHI. It is reduced, but not extinguished by early therapy: DNA containing cells are still detectable after months of successful viremia suppression. To define the best method to measure low level viral replication, we determined the extent of HIV reservoir in 11 acutely infected patients and evaluated how it is renewed even during successful treatment.
Eleven acutely infected HIV patients were included in the study. Three where not treated with antiretroviral drugs while 8 underwent early aggressive antiretroviral treatment (HAART) which, in 3 cases, was associated to cyclosporin A (CsA) administration. HIV viremia was monitored by commercially available methods while HIV-DNA and cellular RNA quantitation were obtained by in house PCR and RT-PCR respectively, in the gag region.
Significant CD4 recover and HIV viremia suppression were reached in a mean period of three to six months in all treated patients. The course of the HIV-DNA and of cellular HIV RNA reduction showed a similar trend. This variation was slower, if compared to plasma viremia and never reached undetectable levels, justifying the rebound of viremia observed at therapy interruption.
These data suggest and confirm that complete abolition of viral replication is not achieved and viral reservoir may be re-expanded even after short term rebound of viremia. Scheduling of possible structured therapy interruption should be designed based on multiple virological parameters and on the individual characteristics of the patients.
HIV-1储存库在PHI期间早期建立。它会减少,但早期治疗无法将其消除:在成功抑制病毒血症数月后,仍可检测到含DNA的细胞。为了确定测量低水平病毒复制的最佳方法,我们测定了11例急性感染患者的HIV储存库程度,并评估了即使在成功治疗期间它是如何更新的。
11例急性感染HIV的患者纳入本研究。3例未接受抗逆转录病毒药物治疗,而8例接受了早期积极的抗逆转录病毒治疗(HAART),其中3例联合使用环孢素A(CsA)。通过商用方法监测HIV病毒血症,同时分别通过内部PCR和RT-PCR在gag区域进行HIV-DNA和细胞RNA定量。
所有接受治疗的患者在三到六个月的平均时间内实现了显著的CD4恢复和HIV病毒血症抑制。HIV-DNA和细胞HIV RNA减少的过程显示出相似的趋势。与血浆病毒血症相比,这种变化较慢,且从未达到不可检测的水平,这解释了在治疗中断时观察到的病毒血症反弹。
这些数据表明并证实,即使在病毒血症短期反弹后,也无法完全消除病毒复制,病毒储存库可能会重新扩大。应根据多种病毒学参数和患者的个体特征来设计可能的结构化治疗中断计划。