Resistance Testing for Management of HIV Virologic Failure in Sub-Saharan Africa : An Unblinded Randomized Controlled Trial.
Resistance Testing for Management of HIV Virologic Failure in Sub-Saharan Africa : An Unblinded Randomized Controlled Trial.
复制标题
DOI：
10.7326/m21-2229
复制
发表时间：
2021-12
影响因子：
39.2
通讯作者：
Marconi VC
中科院分区：
文献类型：
--
作者：
Siedner MJ;Moosa MS;McCluskey S;Gilbert RF;Pillay S;Aturinda I;Ard K;Muyindike W;Musinguzi N;Masette G;Pillay M;Moodley P;Brijkumar J;Rautenberg T;George G;Gandhi RT;Johnson BA;Sunpath H;Bwana MB;Marconi VC
HIV病毒学失败预示着耐药性和死亡率的发展。基因型耐药性检测（GRT）是高收入环境中病毒学失败后的标准治疗方法，但在撒哈拉以南非洲很少实施。评估GRT在改善撒哈拉以南非洲一线治疗失败的HIV感染者的病毒学抑制率方面的有效性。实用、非盲、随机对照试验。（ClinicalTrials.gov：NCT 02787499）乌干达和南非公共部门的门诊艾滋病诊所。接受一线抗逆转录病毒治疗的成人，近期HIV RNA病毒载量为1000拷贝/mL或更高。参与者被随机分配接受标准治疗（SOC），包括依从性咨询会议和重复病毒载量检测，或立即GRT。关注的主要结局是入组后9个月达到HIV RNA病毒载量低于200拷贝/mL。该试验招募了840人，在各国之间平均分配。大约一半（51%）是妇女。大多数（72%）在入组时接受替诺福韦、恩曲他滨和依法韦仑方案。入组后9个月，GRT组（63% [263/417]）和SOC组（61% [256/423];比值比[OR]，1.11 [95%CI，0.83 - 1.49]; P = 0.46）的病毒学抑制率无差异。在9个月时持续失败（HIV RNA病毒载量≥1000拷贝/mL）的受试者中，SOC组的耐药率较高（76% [78/103] vs. 59% [48/82]; OR，2.30 [CI，1.22至4.35]; P = 0.014）。其他次要结局，包括9个月生存率和护理保留率，在两组之间相似。参与者在入组时接受非核苷类逆转录酶靶向治疗，限制了研究结果的普遍性。在乌干达和南非，一线病毒学治疗失败后在常规治疗中增加GRT并没有提高再抑制率。
Virologic failure in HIV predicts the development of drug resistance and mortality. Genotypic resistance testing (GRT), which is the standard of care after virologic failure in high-income settings, is rarely implemented in sub-Saharan Africa. To estimate the effectiveness of GRT for improving virologic suppression rates among people with HIV in sub-Saharan Africa for whom first-line therapy fails. Pragmatic, unblinded, randomized controlled trial. (ClinicalTrials.gov: NCT02787499) Ambulatory HIV clinics in the public sector in Uganda and South Africa. Adults receiving first-line antiretroviral therapy with a recent HIV RNA viral load of 1000 copies/mL or higher. Participants were randomly assigned to receive standard of care (SOC), including adherence counseling sessions and repeated viral load testing, or immediate GRT. The primary outcome of interest was achievement of an HIV RNA viral load below 200 copies/mL 9 months after enrollment. The trial enrolled 840 persons, divided equally between countries. Approximately half (51%) were women. Most (72%) were receiving a regimen of tenofovir, emtricitabine, and efavirenz at enrollment. The rate of virologic suppression did not differ 9 months after enrollment between the GRT group (63% [263 of 417]) and SOC group (61% [256 of 423]; odds ratio [OR], 1.11 [95% CI, 0.83 to 1.49]; P = 0.46). Among participants with persistent failure (HIV RNA viral load ≥1000 copies/mL) at 9 months, the prevalence of drug resistance was higher in the SOC group (76% [78 of 103] vs. 59% [48 of 82]; OR, 2.30 [CI, 1.22 to 4.35]; P = 0.014). Other secondary outcomes, including 9-month survival and retention in care, were similar between groups. Participants were receiving nonnucleoside reverse transcriptase inhibitor–based therapy at enrollment, limiting the generalizability of the findings. The addition of GRT to routine care after first-line virologic failure in Uganda and South Africa did not improve rates of resuppression.