Incidence of switching to second-line antiretroviral therapy and its predictors among children on antiretroviral therapy at general hospitals, Northern Ethiopia: A survival analysis

BACKGROUND: With expanding access to pediatric antiretroviral therapy, several patients in the developing world were switched to the second-line regimen, and some require third-line medications. A delay in a second-line switch is associated with an increased risk of mortality and other undesired therapeutic outcomes, drives up program costs, and challenges the pediatric antiretroviral therapy service. Nevertheless, there remain limited and often conflicting estimates on second-line antiretroviral therapy use during childhood, especially in resource-limited settings like Ethiopia. Thus, this study intended to determine the incidence and predictors of switching to second-line antiretroviral therapy among children. METHODS: A retrospective cohort study was conducted by reviewing records of 424 randomly selected children on first-line antiretroviral therapy from January 2014 to December 2018 at public hospitals in the Central and Southern Zones of Tigray, Northern Ethiopia. Data were collected using extraction tool; entered into Epi-data; cleaned, and analyzed by STATA version-14. Kaplan-Meier curve, log-rank test, and life table were used for data description and adjusted hazard ratios and p-value for analysis by Cox proportional hazard regression. Variables at a P-value of ≤0.20 in the bi-variable analysis were taken to multivariable analysis. Finally, statistical significance was declared at a P-value of ≤0.05. RESULTS AND CONCLUSION: Analysis was conducted on 424 charts with a total person-time observation of 11686.1 child-months and an incidence switch rate of 5.6 (95%CI: 4.36–7.09) per 1000 child-month-observations. Being orphan [AHR = 2.36; 95%CI: 1.10–5.07], suboptimal adherence [AHR = 2.10; 95% CI: 1.12–3.92], drug toxicity [AHR = 7.05; 95% CI: 3.61–13.75], advanced latest clinical stage [AHR = 2.75; 95%CI: 1.05–7.15], and tuberculosis co-infection at baseline [AHR = 3.08; 95%CI: 1.26–7.51] were significantly associated with switch to second-line antiretroviral therapy regimen. Moreover, a long duration of follow-up [AHR = 0.75; 95% CI: 0.71–0.81] was associated with decreased risk of switching. Hence, it is better to prioritize strengthening the focused evaluation of tuberculosis co-infection and treatment failure with continuous adherence monitoring. Further research is also needed to evaluate the effect of drug resistance.