Palmisano Lucia, Giuliano Marina, Bucciardini Raffaella, Fragola Vincenzo, Andreotti Mauro, Galluzzo Clementina, Pirillo Maria F, Weimer Liliana E, Arcieri Romano, Germinario Elena A P, Amici Roberta, Mancini Maria Grazia, Monforte Antonella d'Arminio, Castelli Francesco, Caramello Pietro, Vella Stefano
Department of Drug Research and Evaluation, Instituto Superiore di Sanità, Rome, Italy.
J Acquir Immune Defic Syndr. 2007 Sep 1;46(1):39-47.
Factors influencing the outcome of structured treatment interruptions (STIs) in HIV chronic infection are not fully elucidated.
In ISS-PART, 273 subjects were randomly assigned to arm A (137 assigned to continuous highly active antiretroviral therapy [HAART]) and arm B (136 assigned to 5 STIs of 1, 1, 2, 2, and 3 months' duration, each followed by 3 months of therapy). Main outcome measures were the proportion of subjects with a CD4 count >500 cells/mm3, the rate of virologic failure, and the emergence of resistance at 24 months.
The proportion of subjects with a CD4 count >500 cells/mm3 was higher in arm A than in arm B (86.5% vs. 69.1%; P = 0.0075). Pre-HAART CD4 cell count and male gender were independent predictors of a CD4 count >500 cells/mm3 in arm B. The overall risk of virologic failure was not increased in arm B; however, it was higher in the 38 subjects who had resistance mutations in the rebounding virus. Archived mutations at baseline and the use of a regimen that included an unboosted protease inhibitor (PI), compared with nonnucleoside reverse transcriptase inhibitor-based HAART, independently predicted the emergence of plasma mutations during STI (P = 0.002 for DNA mutations and P = 0.048 for PI-based HAART).
Our results suggest that patients with preexisting mutations and treated with unboosted PI-based HAART should not be enrolled in studies of time-fixed treatment interruptions, being at higher risk of developing plasma mutations during STI and virologic failure at therapy reinstitution.
影响HIV慢性感染中结构化治疗中断（STI）结果的因素尚未完全阐明。
在ISS-PART研究中，273名受试者被随机分配至A组（137名接受持续高效抗逆转录病毒治疗[HAART]）和B组（136名接受5次分别为期1、1、2、2和3个月的STI，每次STI后接受3个月治疗）。主要结局指标为24个月时CD4细胞计数>500个/mm³的受试者比例、病毒学失败率和耐药性出现情况。
A组CD4细胞计数>500个/mm³的受试者比例高于B组（86.5%对69.1%；P = 0.0075）。HAART治疗前的CD4细胞计数和男性性别是B组中CD4细胞计数>500个/mm³的独立预测因素。B组的总体病毒学失败风险未增加；然而，在反弹病毒中存在耐药突变的38名受试者中该风险更高。与基于非核苷类逆转录酶抑制剂的HAART相比，基线时的存档突变以及使用包含未增强蛋白酶抑制剂（PI）的方案可独立预测STI期间血浆突变的出现（DNA突变为P = 0.002，基于PI的HAART为P = 0.048）。
我们的结果表明，存在既往突变且接受未增强PI类HAART治疗的患者不应纳入固定时间治疗中断的研究，因为他们在STI期间发生血浆突变以及治疗重新开始时出现病毒学失败的风险更高。
