Shoko Claris, Chikobvu Delson
Department of Mathematical Statistics and Actuarial Sciences, University of the Free State, Box 339, Bloemfontein, 9300, South Africa.
Theor Biol Med Model. 2018 Jul 16;15(1):10. doi: 10.1186/s12976-018-0082-0.
Antiretroviral therapy (ART) has become the standard of care for patients with HIV infection in South Africa and has led to the reduction in AIDS related morbidity and mortality. In developing countries, the nucleosides reverse transcriptase inhibitors (NRTIs) class are widely used because of their low production costs. However patients treated with NRTIs develop varying degree of toxicity after long-term therapy. For this study patients are administered with a triple therapy of two NRTIs and one non-nucleoside reverse transcriptase inhibitor (NNRTI).
In this study the progression of HIV in vivo is divided into some viral load states and a continuous time-homogeneous model is fitted to assess the effects of covariates namely gender, age, CD4 baseline, viral load baseline, lactic acidosis, peripheral neuropathy, non-adherence and resistance to treatment on transition intensities between the states. Effects of different drug combinations on transition intensities are also assessed.
The results show no gender differences on transition intensities. The likelihood ratio test shows that the continuous time Markov model for the effects of the covariates including combination give a significantly better fit to the observed data. From almost all states, rates of viral suppression were higher than rates of viral rebound except for patients in state 2 (viral load between 50 and 10,000 copies/mL) where rates of viral rebound to state 3 (viral load between 10,000 and 100,000 copies/mL) were higher than rates of viral suppression to undetectable levels. For this transition, confidence intervals were very small. This was quite notable for patients who were administered with AZT-3TC-LPV/r and FTC-TDF-EFV. Although patients on d4T-3TC-EFV also had higher rates of viral rebound from state 2 than suppression, the difference was not significant.
From these findings, we can conclude that administering of any HIV drug regimen is better when based on the viral load level of an HIV+ patient. Before initiation of treatment, patients should be well equipped on how antiretroviral drugs operate including possibilities of toxicity in order to reduce chances of non-adherence to treatment. There should also be a good relationship between patient and health-care-giver to ensure proper adherence to treatment. Uptake of therapy by young patients should be closely monitored by adopting pill counting every time they come for review.
抗逆转录病毒疗法(ART)已成为南非艾滋病毒感染患者的标准治疗方法,并导致与艾滋病相关的发病率和死亡率有所降低。在发展中国家,核苷类逆转录酶抑制剂(NRTIs)因其生产成本低而被广泛使用。然而,接受NRTIs治疗的患者在长期治疗后会出现不同程度的毒性。在本研究中,患者接受两种NRTIs和一种非核苷类逆转录酶抑制剂(NNRTI)的三联疗法。
在本研究中,将体内艾滋病毒的进展分为若干病毒载量状态,并拟合一个连续时间齐次模型,以评估协变量(即性别、年龄、CD4基线、病毒载量基线、乳酸性酸中毒、周围神经病变、治疗依从性差和治疗耐药性)对各状态之间转移强度的影响。还评估了不同药物组合对转移强度的影响。
结果表明,转移强度不存在性别差异。似然比检验表明,包含组合因素在内的协变量效应的连续时间马尔可夫模型对观测数据的拟合效果显著更好。除了处于状态2(病毒载量在50至10,000拷贝/毫升之间)的患者外,几乎所有状态下病毒抑制率均高于病毒反弹率,处于状态2的患者从状态2反弹至状态3(病毒载量在10,000至100,000拷贝/毫升之间)的病毒反弹率高于病毒抑制至检测不到水平的比率。对于这种转移,置信区间非常小。对于接受齐多夫定-拉米夫定-洛匹那韦/利托那韦(AZT-3TC-LPV/r)和替诺福韦酯-恩曲他滨-依非韦伦(FTC-TDF-EFV)治疗的患者而言,这一点尤为显著。尽管接受司他夫定-拉米夫定-依非韦伦(d4T-3TC-EFV)治疗的患者从状态2的病毒反弹率也高于抑制率,但差异并不显著。
从这些研究结果可以得出结论,根据艾滋病毒阳性患者的病毒载量水平来施用任何艾滋病毒药物方案会更好。在开始治疗前,应让患者充分了解抗逆转录病毒药物的作用机制,包括毒性可能性,以减少治疗依从性差的几率。患者与医护人员之间还应建立良好的关系,以确保正确遵守治疗方案。每次复诊时应通过清点药片来密切监测年轻患者的治疗依从情况。