Barbour Jason D, Hecht Frederick M, Wrin Terri, Liegler Teri J, Ramstead Clarissa A, Busch Michael P, Segal Mark R, Petropoulos Christos J, Grant Robert M
Gladstone Institute of Virology and Immunology, San Francisco, California 94141-9100, USA.
AIDS. 2004 Aug 20;18(12):1683-9. doi: 10.1097/01.aids.0000131391.91468.ff.
Primary, or transmitted, drug resistance is common among treatment naive patients recently infected with HIV-1, and impairs response to anti-retroviral therapy. We previously observed that patients with secondary resistance (developed in response to anti-retroviral treatment) who chose to stop an anti-retroviral regimen experience rapid overgrowth of drug resistant viruses by wild-type virus of higher pol replication capacity. We sought to determine if primary drug resistance would be lost at a rapid rate, and viral pol replication capacity would increase, in the absence of treatment.
We tracked drug resistance phenotype, genotype, viral pol replication capacity (single cycle recombinant assay incorporating a segment of the patient pol gene [pol RC]), plasma HIV-1 RNA, and CD4 T cell counts in the absence of treatment among patients in early HIV-1 infection.
Six of 22 patients had evidence of primary drug resistance to at least one class of drug; three resistant to protease inhibitors, three resistant to non-nucleoside reverse transcriptase inhibitors, and four resistant to nucleoside reverse transcriptase inhibitors. All six patients maintained evidence of drug resistance for the period of observation. Among patients with baseline primary drug resistance pol RC did not increase over time.
The selection environment of early infection is determined by immune pressure, and stochastic events, not viral pol replication capacity. In contrast to secondary resistant infections that are rapidly overgrown when therapy is stopped, primary drug resistance persists over time. Surveillance and clinical detection of primary resistance is feasible in the first year of infection.
原发性（即传播性）耐药在近期感染HIV-1的初治患者中很常见，并会损害抗逆转录病毒治疗的反应。我们之前观察到，选择停用抗逆转录病毒治疗方案的继发性耐药（因抗逆转录病毒治疗而产生）患者，其耐药病毒会被具有更高聚合酶复制能力的野生型病毒迅速过度生长。我们试图确定在未接受治疗的情况下，原发性耐药是否会迅速消失，以及病毒聚合酶复制能力是否会增加。
我们在未接受治疗的情况下，追踪了早期HIV-1感染患者的耐药表型、基因型、病毒聚合酶复制能力（包含患者聚合酶基因片段的单循环重组试验[聚合酶RC]）、血浆HIV-1 RNA和CD4 T细胞计数。
22名患者中有6名有对至少一类药物原发性耐药的证据；3名对蛋白酶抑制剂耐药，3名对非核苷类逆转录酶抑制剂耐药，4名对核苷类逆转录酶抑制剂耐药。所有6名患者在观察期内均保持耐药证据。在基线存在原发性耐药的患者中，聚合酶RC并未随时间增加。
早期感染的选择环境由免疫压力和随机事件决定，而非病毒聚合酶复制能力。与停止治疗时会迅速被过度生长的继发性耐药感染不同，原发性耐药会随时间持续存在。在感染的第一年对原发性耐药进行监测和临床检测是可行的。
