Lee Guinevere Q, Bangsberg David R, Muzoora Conrad, Boum Yap, Oyugi Jessica H, Emenyonu Nneka, Bennett John, Hunt Peter W, Knapp David, Brumme Chanson J, Harrigan P Richard, Martin Jeffrey N
1 B.C. Centre for Excellence in HIV/AIDS , Vancouver, BC, Canada .
AIDS Res Hum Retroviruses. 2014 Sep;30(9):896-906. doi: 10.1089/AID.2014.0043. Epub 2014 Jul 29.
Few reports have examined the impact of HIV-1 transmitted drug resistance (TDR) in resource-limited settings where there are fewer regimen choices and limited pretherapy/posttherapy resistance testing. In this study, we examined TDR prevalence in Kampala and Mbarara, Uganda and assessed its virologic consequences after antiretroviral therapy initiation. We sequenced the HIV-1 protease/reverse transcriptase from n=81 and n=491 treatment-naive participants of the Uganda AIDS Rural Treatment Outcomes (UARTO) pilot study in Kampala (AMU 2002-2004) and main cohort in Mbarara (MBA 2005-2010). TDR-associated mutations were defined by the WHO 2009 surveillance mutation list. Posttreatment viral load data were available for both populations. Overall TDR prevalence was 7% (Kampala) and 3% (Mbarara) with no significant time trend. There was a slight but statistically nonsignificant trend indicating that the presence of TDR was associated with a worse treatment outcome. Virologic suppression (≤400 copies/ml within 6 months posttherapy initiation) was achieved in 87% and 96% of participants with wildtype viruses versus 67% and 83% of participants with TDR (AMU, MBA p=0.2 and 0.1); time to suppression (log-rank p=0.3 and p=0.05). Overall, 85% and 96% of study participants achieved suppression regardless of TDR status. Surprisingly, among the TDR cases, approximately half still achieved suppression; the presence of pretherapy K103N while on nevirapine and fewer active drugs in the first regimen were most often observed with failures. The majority of patients benefited from the local HIV care system even without resistance monitoring. Overall, TDR prevalence was relatively low and its presence did not always imply treatment failure.
在治疗方案选择较少且治疗前/治疗后耐药性检测有限的资源有限环境中，很少有报告研究过HIV-1传播耐药性（TDR）的影响。在本研究中，我们调查了乌干达坎帕拉和姆巴拉拉的TDR流行情况，并评估了开始抗逆转录病毒治疗后其病毒学后果。我们对乌干达艾滋病农村治疗结果（UARTO）试点研究（2002 - 2004年坎帕拉）的81名初治参与者以及姆巴拉拉主要队列（2005 - 2010年MBA）的491名初治参与者的HIV-1蛋白酶/逆转录酶进行了测序。TDR相关突变由世界卫生组织2009年监测突变列表定义。两个群体均有治疗后的病毒载量数据。总体TDR流行率为7%（坎帕拉）和3%（姆巴拉拉），且无显著的时间趋势。有一个轻微但在统计学上无显著意义的趋势表明，TDR的存在与较差的治疗结果相关。野生型病毒参与者中分别有87%和96%在治疗开始后6个月内实现了病毒学抑制（≤400拷贝/毫升），而TDR参与者中这一比例分别为67%和83%（AMU、MBA，p值分别为0.2和0.1）；实现抑制的时间（对数秩检验，p值分别为0.3和0.05）。总体而言，无论TDR状态如何，85%和96%的研究参与者都实现了病毒抑制。令人惊讶的是，在TDR病例中，约一半仍实现了病毒抑制；治疗前使用奈韦拉平时有K103N突变以及首个治疗方案中活性药物较少的情况最常出现在治疗失败的病例中。即使没有耐药性监测，大多数患者也从当地的HIV护理系统中受益。总体而言，TDR流行率相对较低，其存在并不总是意味着治疗失败。
