Abstract
Background: Antiretroviral therapy (ART) impact has prolonged survival of people living with HIV. We evaluated HIV disease progression among ART patients using routinely collected patient-level data between 2004 and 2017 in Zimbabwe.Methods: We partitioned HIV disease progression into four transient CD4 cell counts states: state 1 (CD4 ≥ 500 cells/μl), state 2 (350 cells/μl ≤ CD4 < 500 cells/μl), state 3 (200 cells/μl ≤ CD4 < 350 cells/μl), state 4 (CD4 < 200 cells/μl), and the absorbing state death (state 5). We proposed a semiparametric time-homogenous multistate Markov model to estimate bidirectional transition rates. Covariate effects (age, gender, ART initiation period, and health facility level) on the transition rates were assessed.Results: We analyzed 204,289 clinic visits by 63,422 patients. There were 24,325 (38.4%) patients in state 4 (CD4 < 200) at ART initiation, and 7,995 (12.6%) deaths occurred by December 2017. The overall mortality rate was 3.9 per 100 person-years. The highest mortality rate of 5.7 per 100 person-years (4,541 deaths) was from state 4 (CD4 < 200) compared to other states. Mortality rates decreased with increase in time since ART initiation. Health facility type was the strongest predictor for immune recovery. Provincial or central hospital patients showed a diminishing dose–response effect on immune recovery by state from a hazard ratio (HR) of 8.30 [95% confidence interval (95% CI), 6.64–10.36] (state 4 to 3) to HR of 3.12 (95% CI, 2.54–4.36) (state 2 to 1) compared to primary healthcare facilities. Immune system for male patients was more likely to deteriorate, and they had a 32% increased mortality risk (HR, 1.32; 95% CI, 1.23–1.42) compared to female patients. Elderly patients (45+ years) were more likely to immune deteriorate compared to 25–34 years age group: HR, 1.35; 95% CI, 1.18–1.54; HR, 1.56; 95% CI, 1.34–1.81 and HR, 1.53; 95% CI, 1.32–1.79 for states 1 to 2, state 2 to 3, and states 3 to 4, respectively.Conclusion: Immune recovery was pronounced among provincial or central hospitals. Male patients with lower CD4 cell counts were at a higher risk of immune deterioration and mortality, while elderly patients were more likely to immune deteriorate. Early therapeutic interventions when the immune system is relatively stable across gender and age may contain mortality and increase survival outcomes. Interventions which strengthen ART services in primary healthcare facilities are essential.
Highlights
Over the last 15 years, remarkable strides have been made to tackle the human immunodeficiency virus (HIV) pandemic globally
Antiretroviral therapy (ART) drugs help boost the immune system of the people living with HIV (PLHIV) [5], which leads to viral load suppression, and an increase in CD4 cell counts
Patients who were aged 45 years and above were more likely to immune deteriorate compared to 25–34 years age group: HR, 1.35; 95% CI, 1.18–1.54; HR, 1.56; 95% CI, 1.34–1.81, and HR, 1.53; 95% CI, 1.32–1.79 for state 1 to 2, state 2 to 3, and state 3 to 4, respectively
Summary
Over the last 15 years, remarkable strides have been made to tackle the human immunodeficiency virus (HIV) pandemic globally. ART drugs help boost the immune system of the PLHIV [5], which leads to viral load suppression, and an increase in CD4 cell counts. Both CD4 cell counts and viral load are key prognostic markers in measuring HIV disease progression [6]. The World Health Organization (WHO) recommends the use of viral load in monitoring HIV disease progression among ART patients. Over the years, CD4 cell counts have been extensively used as a marker for HIV disease progression. We evaluated HIV disease progression among ART patients using routinely collected patient-level data between 2004 and 2017 in Zimbabwe
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