This study aimed to jointly model HIV disease progression patterns based on viral load (VL) among adult ART patients adjusting for the time-varying “incremental transients states” variable, and the CD4 cell counts orthogonal variable in a single 5-stage time-homogenous multistate Markov model. We further jointly mapped the relative risks of HIV disease progression outcomes (detectable VL (VL ≥ 50copies/uL) and immune deterioration (CD4 < 350cells/uL) at the last observed visit) conditional not to have died or become loss to follow-up (LTFU). Secondary data analysis of individual-level patients on ART was performed. Adjusted transition intensities, hazard ratios (HR) and regression coefficients were estimated from the joint multistate model of VL and CD4 cell counts. The mortality and LTFU transition rates defined the extent of patients’ retention in care. Joint mapping of HIV disease progression outcomes after ART initiation was done using the Bayesian intrinsic Multivariate Conditional Autoregressive prior model. The viral rebound from the undetectable state was 1.78times more likely compared to viral suppression among patients with VL ranging from 50-1000copies/uL. Patients with CD4 cell counts lower than expected had a higher risk of viral increase above 1000copies/uL and death if their VL was above 1000copies/uL (state 2 to 3 (λ23): HR = 1.83 and (λ34): HR = 1.42 respectively). Regarding the time-varying effects of CD4 cell counts on the VL transition rates, as the VL increased, (λ12 and λ23) the transition rates increased with a decrease in the CD4 cell counts over time. Regardless of the individual’s VL, the transition rates to become LTFU decreased with a decrease in CD4 cell counts. We observed a strong shared geographical pattern of 66% spatial correlation between the relative risks of detectable VL and immune deterioration after ART initiation, mainly in Matabeleland North. With high rates of viral rebound, interventions which encourage ART adherence and continual educational support on the barriers to ART uptake are crucial to achieve and sustain viral suppression to undetectable levels. Area-specific interventions which focus on early ART screening through self-testing, behavioural change campaigns and social support strategies should be strengthened in heavily burdened regions to sustain the undetectable VL. Sustaining undetectable VL lowers HIV transmission in the general population and this is a step towards achieving zero HIV incidences by 2030.

中文翻译：

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调整 CD4 正交变量的病毒载量马尔科夫模型和津巴布韦 ART 患者 HIV 免疫学结果的多变量条件自回归映射

本研究旨在基于成人 ART 患者的病毒载量 (VL) 联合建模 HIV 疾病进展模式，调整随时间变化的“增量瞬变状态”变量，以及单个 5 阶段时间均质中的 CD4 细胞计数正交变量多态马尔可夫模型。我们进一步联合绘制了 HIV 疾病进展结果的相对风险（可检测到的 VL（VL ≥ 50copies/uL）和最后一次观察到的免疫恶化（CD4 < 350cells/uL））条件是未死亡或失访(LTFU)。对接受 ART 的个体水平患者进行了二次数据分析。从 VL 和 CD4 细胞计数的联合多状态模型估计调整后的转换强度、风险比 (HR) 和回归系数。死亡率和 LTFU 转换率定义了患者在护理中的保留程度。ART 启动后 HIV 疾病进展结果的联合映射是使用贝叶斯内在多变量条件自回归先验模型完成的。在 VL 范围为 50-1000copies/uL 的患者中，与病毒抑制相比，病毒从无法检测状态反弹的可能性是病毒抑制的 1.78 倍。CD4 细胞计数低于预期的患者病毒增加超过 1000copies/uL 和死亡的风险更高，如果他们的 VL 高于 1000copies/uL（状态 2 到 3（λ23）：HR = 1.83 和（λ34）：HR = 1.42） ）。关于 CD4 细胞计数对 VL 转变率的时变影响，随着 VL 的增加，（λ12 和 λ23）转变率随着 CD4 细胞计数的减少而增加。无论个体的 VL 是多少，转变为 LTFU 的转化率都随着 CD4 细胞计数的减少而降低。我们观察到 ART 启动后可检测到的 VL 的相对风险与免疫恶化之间存在 66% 的空间相关性的强烈共享地理模式，主要是在北马塔贝莱兰。由于病毒反弹率高，鼓励 ART 依从性和持续教育支持对 ART 摄取障碍的干预对于实现和维持病毒抑制至无法检测的水平至关重要。应在负担沉重的地区加强通过自我测试、行为改变运动和社会支持策略进行早期 ART 筛查的特定地区干预措施，以维持无法检测到的 VL。