Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda.
Clinical Epidemiology Unit, School of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda.
BMC Infect Dis. 2021 Jun 1;21(1):513. doi: 10.1186/s12879-021-06220-6.
In resource-limited settings, sputum smear conversion is used to document treatment response. Many People living with HIV (PLHIV) are smear-negative at baseline. The Xpert MTB/RIF test can indirectly measure bacterial load through cycle threshold (ct) values. This study aimed to determine if baseline Xpert MTB/RIF could predict time to culture negativity in PLHIV with newly diagnosed TB.
A subset of 138 PLHIV from the 'SOUTH' study on outcomes related to TB and antiretroviral drug concentrations were included. Bacterial load was estimated by Mycobacterium Growth Indicator Tubes (MGIT) culture time-to-positivity (TTP) and Lowenstein Jensen (LJ) colony counts. Changes in TTP and colony counts were analyzed with Poisson Generalised Estimating Equations (GEE) and multilevel ordered logistic regression models, respectively, while time to culture negativity analysed with Cox proportional hazard models. ROC curves were used to explore the accuracy of the ct value in predicting culture negativity.
A total of 81 patients (58.7%) were males, median age 34 (IQR 29 ̶ 40) years, median CD4 cell count of 180 (IQR 68 ̶ 345) cells/μL and 77.5% were ART naive. The median baseline ct value was 25.1 (IQR 21.0 ̶ 30.1). A unit Increase in the ct value was associated with a 5% (IRR = 1.05 95% CI 1.04 ̶ 1.06) and 3% (IRR = 1.03 95% CI 1.03 ̶ 1.04) increase in TTP at week 2 and 4 respectively. With LJ culture, a patient's colony grade was reduced by 0.86 times (0R = 0.86 95% CI 0.74 ̶ 0.97) at week 2 and 0.84 times (OR = 0.84 95% CI 0.79 ̶ 0.95 P = 0.002) at week 4 for every unit increase in the baseline ct value. There was a 3% higher likelihood of earlier conversion to negativity for every unit increase in the ct value. A ct cut point ≥28 best predicted culture negativity at week 4 with a sensitivity of 91. 7% & specificity 53.7% while a cut point ≥23 best predicted culture negativity at week 8.
Baseline Xpert MTB/RIF ct values predict sputum conversion in PLHIV on anti-TB treatment. Surrogate biomarkers for sputum conversion in PLHIV are still a research priority.
在资源有限的环境下，痰涂片转化被用来记录治疗反应。许多艾滋病毒感染者（PLHIV）在基线时为痰涂片阴性。Xpert MTB/RIF 测试可以通过循环阈值（ct）值间接测量细菌载量。本研究旨在确定基线 Xpert MTB/RIF 是否可以预测新诊断为结核病的 PLHIV 培养阴性的时间。
从与结核病和抗逆转录病毒药物浓度相关的“SOUTH”研究中选择了 138 名 PLHIV 作为亚组。细菌载量通过 Mycobacterium Growth Indicator Tubes（MGIT）培养时间至阳性（TTP）和 Lowenstein Jensen（LJ）菌落计数来估计。TTP 和菌落计数的变化分别通过泊松广义估计方程（GEE）和多水平有序逻辑回归模型进行分析，而培养阴性的时间通过 Cox 比例风险模型进行分析。ROC 曲线用于探索 ct 值预测培养阴性的准确性。
共有 81 名患者（58.7%）为男性，中位年龄为 34（IQR 29 至 40）岁，中位 CD4 细胞计数为 180（IQR 68 至 345）细胞/μL，77.5%为抗逆转录病毒药物治疗初治。基线 ct 值中位数为 25.1（IQR 21.0 至 30.1）。ct 值增加一个单位与第 2 周和第 4 周的 TTP 分别增加 5%（IRR=1.05 95%CI 1.04 至 1.06）和 3%（IRR=1.03 95%CI 1.03 至 1.04）相关。在 LJ 培养中，基线 ct 值每增加一个单位，第 2 周和第 4 周的菌落等级分别降低 0.86 倍（0R=0.86 95%CI 0.74 至 0.97）和 0.84 倍（OR=0.84 95%CI 0.79 至 0.95 P=0.002）。ct 值每增加一个单位，第 2 周和第 4 周培养阴性的可能性分别增加 3%。ct 值每增加一个单位，第 4 周培养阴性的可能性增加 3%。ct 值≥28 时，第 4 周培养阴性的可能性最高，敏感性为 91.7%，特异性为 53.7%；而 ct 值≥23 时，第 8 周培养阴性的可能性最高。
基线 Xpert MTB/RIF ct 值可预测抗结核治疗中 PLHIV 的痰转化。PLHIV 痰转化的替代生物标志物仍是研究重点。
