Shao Humphrey J, Crump John A, Ramadhani Habib O, Uiso Leonard O, Ole-Nguyaine Sendui, Moon Andrew M, Kiwera Rehema A, Woods Christopher W, Shao John F, Bartlett John A, Thielman Nathan M
Kilimanjaro Christian Medical Centre, Moshi, Tanzania.
AIDS Res Hum Retroviruses. 2009 Dec;25(12):1277-85. doi: 10.1089/aid.2009.0100.
Fixed dose combination abacavir/lamivudine/zidovudine (ABC/3TC/ZDV) among HIV-1 and tuberculosis (TB)-coinfected patients was evaluated and outcomes between early vs. delayed initiation were compared. In a randomized, pilot study conducted in the Kilimanjaro Region of Tanzania, HIV-infected inpatients with smear-positive TB and total lymphocyte count <1200/mm(3) were randomized to initiate ABC/3TC/ZDV either 2 (early) or 8 (delayed) weeks after commencing antituberculosis therapy and were followed for 104 weeks. Of 94 patients screened, 70 enrolled (41% female, median CD4 count 103 cells/mm(3)), and 33 in each group completed 104 weeks. Two deaths and 12 serious adverse events (SAEs) were observed in the early arm vs. one death, one clinical failure, and seven SAEs in the delayed arm (p = 0.6012 for time to first grade 3/4 event, SAE, or death). CD4 cell increases were +331 and +328 cells/mm(3), respectively. TB-immune reconstitution inflammatory syndromes (TB-IRIS) were not observed in any subject. Using intent-to-treat (ITT), missing = failure analyses, 74% (26/35) vs. 89% (31/35) randomized to early vs. delayed therapy had HIV RNA levels <400 copies/ml at 104 weeks (p = 0.2182) and 66% (23/35) vs. 74% (26/35), respectively, had HIV RNA levels <50 copies/ml (p = 0.6026). In an analysis in which switches from ABC/3TC/ZDV = failure, those receiving early therapy were less likely to be suppressed to <400 copies/ml [60% (21/35) vs. 86% (30/35), p = 0.030]. TB-IRIS was not observed among the 70 coinfected subjects beginning antiretroviral treatment. ABC/3TC/ZDV was well tolerated and resulted in steady immunologic improvement. Rates of virologic suppression were similar between early and delayed treatment strategies with triple nucleoside regimens when substitutions were allowed.
对合并感染人类免疫缺陷病毒1型（HIV-1）和结核病（TB）的患者使用固定剂量复方制剂阿巴卡韦/拉米夫定/齐多夫定（ABC/3TC/ZDV）进行了评估，并比较了早期与延迟开始治疗的结果。在坦桑尼亚乞力马扎罗地区进行的一项随机试点研究中，将涂片阳性结核病且总淋巴细胞计数<1200/mm³的HIV感染住院患者随机分为两组，一组在开始抗结核治疗后2周（早期）开始使用ABC/3TC/ZDV，另一组在8周（延迟）开始使用，随访104周。在94名筛查的患者中，70名入组（41%为女性，CD4计数中位数为103个细胞/mm³），每组33名患者完成了104周的随访。早期治疗组观察到2例死亡和12例严重不良事件（SAE），延迟治疗组观察到1例死亡、1例临床失败和7例SAE（首次出现3/4级事件、SAE或死亡的时间，p = 0.6012）。CD4细胞增加量分别为+331和+328个细胞/mm³。在任何受试者中均未观察到结核病免疫重建炎症综合征（TB-IRIS）。采用意向性治疗（ITT）、缺失值=失败分析，随机分配到早期治疗组与延迟治疗组的患者中，分别有74%（26/35）和89%（31/35）在104周时HIV RNA水平<400拷贝/ml（p = 0.2182），分别有66%（23/35）和74%（26/35）的患者HIV RNA水平<50拷贝/ml（p = 0.6026）。在一项将从ABC/3TC/ZDV换药视为治疗失败的分析中，接受早期治疗的患者被抑制到<400拷贝/ml的可能性较小[60%（21/35）对86%（30/35），p = 0.030]。在70名开始抗逆转录病毒治疗的合并感染患者中未观察到TB-IRIS。ABC/3TC/ZDV耐受性良好，并导致免疫功能稳步改善。当允许换药时，三联核苷方案的早期和延迟治疗策略的病毒学抑制率相似。
